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Phase 1 Three Part SAD, MAD & Cross-Over Study of ZP-059 in Healthy and Asthmatic Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04229303
Recruitment Status : Completed
First Posted : January 18, 2020
Results First Posted : November 15, 2021
Last Update Posted : November 15, 2021
Sponsor:
Information provided by (Responsible Party):
Zambon SpA

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Allergic Bronchopulmonary Aspergillosis
Interventions Drug: Voriconazole inhaled
Drug: oral voriconazole
Enrollment 58
Recruitment Details

The investigator or his/her representative explained the nature of the study to the subject and answered all questions regarding the study. Subjects had to be informed that their participation was voluntary. Subjects were required to sign a statement of informed consent that met the requirements of UK regulations, ICH E6 GCP guidelines, General Data Protection Regulation, and the IEC or study site requirements.

The authorized person who obtained the informed consent had to also sign the ICF.

Pre-assignment Details

Subjects were screened for eligibility to participate in the study within 28 days before dosing (Day 1). Part 2 and Part 3 subjects who had completed the initial screening visit attended the study site on Day -4 or Day -3, for Covid-19 reverse transcriptase - polymerase chain reaction (RT-PCR) test, together with additional daily tympanic temperature measurements, and other tests as applicable.

Subjects were then be admitted to the study site on the evening of Day -1.

Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd Part 3 - ZP-059 / Oral Voriconazole Part 3 - Oral Voriconazole / ZP-059
Hide Arm/Group Description

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Period Title: Overall Study
Started 6 6 6 6 6 6 6 8 8
Completed 6 6 6 6 6 6 6 8 8
Not Completed 0 0 0 0 0 0 0 0 0
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd Part 3 - ZP-059 / Oral Voriconazole Part 3 - Oral Voriconazole / ZP-059 Total
Hide Arm/Group Description

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Total of all reporting groups
Overall Number of Baseline Participants 6 6 6 6 6 6 6 8 8 58
Hide Baseline Analysis Population Description
Enrolled Set: subjects who passed screening irrespective of whether they received study treatment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 8 participants 8 participants 58 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
8
 100.0%
8
 100.0%
58
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 8 participants 8 participants 58 participants
Female
3
  50.0%
3
  50.0%
3
  50.0%
2
  33.3%
2
  33.3%
2
  33.3%
3
  50.0%
1
  12.5%
2
  25.0%
21
  36.2%
Male
3
  50.0%
3
  50.0%
3
  50.0%
4
  66.7%
4
  66.7%
4
  66.7%
3
  50.0%
7
  87.5%
6
  75.0%
37
  63.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 8 participants 8 participants 58 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  12.5%
1
  12.5%
2
   3.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   3.4%
White
6
 100.0%
5
  83.3%
6
 100.0%
6
 100.0%
5
  83.3%
5
  83.3%
6
 100.0%
6
  75.0%
7
  87.5%
52
  89.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  12.5%
0
   0.0%
1
   1.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United Kingdom Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 8 participants 8 participants 58 participants
6 6 6 6 6 6 6 8 8 58
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAE)
Hide Description An AE is any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of IMP, whether or not considered related to the study IMP.
Time Frame Part 1: screening (Day -28 to -1) to follow-up (8 to 12 days after last dose); part 2: screening (Day -28 to -1) to follow-up (11-17 days after last dose); Part 3: screening (Day -28 to -1) to follow-up (8-12 days after last dose of study drug).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAF): subjects who received at least 1 IMP dose, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd Part 3 - ZP-059 20mg Part 3 - Oral Voriconazole 200mg
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 6 6 6 6 6 6 6 16 16
Measure Type: Number
Unit of Measure: participants
Total number of subjects with at least 1 TEAE 0 3 2 2 5 4 4 9 7
Total number of subjects with at least 1 serious TEAE 0 0 0 0 0 0 0 0 0
Total number of subjects with at least 1 mild TEAE 0 2 2 1 3 3 2 8 5
Total number of subjects with at least 1 moderate TEAE 0 1 0 1 2 1 2 1 2
Total number of subjects with at least 1 severe TEAE 0 0 0 0 0 0 0 0 0
Total number of subjects with at least 1 treatment-related TEAE 0 0 0 0 4 0 1 7 0
Total number of subjects with at least 1 non treatment-related TEAE 0 3 2 2 1 4 3 2 7
2.Secondary Outcome
Title AUC0-t, AUC0-inf for Voriconazole and N-oxide Voriconazole - Part 1
Hide Description AUC0-t = Area under the serum concentration time curve from time 0 to time t (hours) (AUC0-t) (AUC0-12 for Part 1) AUC0-inf = Area under the serum concentration time curve from time 0 to infinity
Time Frame Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: h*ng/mL
AUC0-t Voriconazole Number Analyzed 6 participants 6 participants 6 participants 6 participants
24.36  (1.45) 73.89  (1.16) 187.76  (1.35) 328.37  (1.19)
AUC0-t N-oxide Voriconazole Number Analyzed 6 participants 6 participants 6 participants 6 participants
298.15  (1.11) 573.55  (1.26) 804.24  (1.11) 1835.81  (1.09)
AUC0-inf Voriconazole Number Analyzed 3 participants 6 participants 6 participants 6 participants
40.00  (1.00) 78.94  (1.18) 203.96  (1.44) 377.19  (1.20)
AUC0-inf N-oxide Voriconazole Number Analyzed 6 participants 5 participants 4 participants 3 participants
337.40  (1.12) 652.99  (1.32) 865.80  (1.07) 1977.21  (1.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for Voriconazole AUC0-t
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method General power constant model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.62
Confidence Interval (2-Sided) 90%
0.424 to 0.821
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for Voriconazole AUC0-t
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0363
Comments [Not Specified]
Method General power linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.21
Confidence Interval (2-Sided) 90%
1.050 to 1.362
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 40mg
Comments Statistics for Voriconazole AUC0-t, 40mg vs 5mg
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean difference
Estimated Value 13.48
Confidence Interval (2-Sided) 90%
10.096 to 17.994
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for N-oxide Voriconazole AUC0-t
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method General power constant model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.85
Confidence Interval (2-Sided) 90%
1.728 to 1.963
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for N-oxide Voriconazole AUC0-t
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0201
Comments [Not Specified]
Method General power linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.87
Confidence Interval (2-Sided) 90%
0.789 to 0.960
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 40mg
Comments Statistics for N-oxide Voriconazole AUC0-t, 40mg vs 5mg
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean difference
Estimated Value 6.16
Confidence Interval (2-Sided) 90%
5.253 to 7.217
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for Voriconazole AUC0-inf
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method General power constant model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.81
Confidence Interval (2-Sided) 90%
0.661 to 0.958
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for Voriconazole AUC0-inf
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1278
Comments [Not Specified]
Method General power linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.12
Confidence Interval (2-Sided) 90%
0.990 to 1.245
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 40mg
Comments Statistics for Voriconazole AUC0-inf, 40mg vs 5mg
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean difference
Estimated Value 9.43
Confidence Interval (2-Sided) 90%
6.834 to 13.012
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for N-oxide Voriconazole AUC0-inf
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method General power constant model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.98
Confidence Interval (2-Sided) 90%
1.860 to 2.106
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for N-oxide Voriconazole AUC0-inf
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0082
Comments [Not Specified]
Method General power linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.79
Confidence Interval (2-Sided) 90%
0.670 to 0.912
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 40mg
Comments Statistics for N-oxide Voriconazole AUC0-inf, 40mg vs 5mg
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean difference
Estimated Value 5.86
Confidence Interval (2-Sided) 90%
4.627 to 7.421
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Cmax for Voriconazole and N-oxide Voriconazole - Part 1
Hide Description Cmax is the highest concentration of a drug in the blood, cerebrospinal fluid, or target organ after a dose is given;
Time Frame Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Voriconazole 8.44  (1.27) 18.52  (1.39) 53.37  (1.32) 94.33  (1.18)
N-oxide voriconazole 57.70  (1.12) 103.16  (1.32) 145.79  (1.30) 286.63  (1.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for Voriconazole Cmax
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2575
Comments [Not Specified]
Method General power constant model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.12
Confidence Interval (2-Sided) 90%
-0.060 to 0.308
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for Voriconazole Cmax
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0491
Comments [Not Specified]
Method General power linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.17
Confidence Interval (2-Sided) 90%
1.030 to 1.316
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 40mg
Comments Statistics for Voriconazole Cmax, 40mg vs 5mg
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean difference
Estimated Value 11.17
Confidence Interval (2-Sided) 90%
8.435 to 14.803
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for N-oxide Voriconazole Cmax
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method General power constant model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.25
Confidence Interval (2-Sided) 90%
1.135 to 1.363
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 10mg, Part 1 - ZP-059 20mg, Part 1 - ZP-059 40mg
Comments Statistics for N-oxide Voriconazole Cmax
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method General power linear model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.74
Confidence Interval (2-Sided) 90%
0.634 to 0.843
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 5mg, Part 1 - ZP-059 40mg
Comments Statistics for N-oxide Voriconazole Cmax, 40mg vs 5mg
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean difference
Estimated Value 4.97
Confidence Interval (2-Sided) 90%
3.946 to 6.254
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Tmax and T1/2 for Voriconazole and N-oxide Voriconazole - Part 1
Hide Description Tmax= Time to maximum concentration (Cmax). T 1/2 = Elimination half-life: the time taken for the plasma concentration to fall by half its original value.
Time Frame Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: hours
Tmax Voriconazole Number Analyzed 6 participants 6 participants 6 participants 6 participants
1.57  (1.11) 1.50  (1.00) 1.50  (1.00) 1.50  (1.00)
Tmax N-oxide voriconazole Number Analyzed 6 participants 6 participants 6 participants 6 participants
1.57  (1.11) 1.50  (1.00) 1.85  (1.29) 1.65  (1.15)
T1/2 Voriconazole Number Analyzed 4 participants 6 participants 6 participants 6 participants
2.67  (1.42) 3.07  (1.09) 3.20  (1.17) 3.63  (1.22)
T1/2 N-oxide voriconazole Number Analyzed 6 participants 6 participants 5 participants 6 participants
3.60  (1.08) 3.59  (1.21) 3.38  (1.27) 4.43  (1.26)
5.Secondary Outcome
Title Kel for Voriconazole and N-oxide Voriconazole - Part 1
Hide Description

Kel (Elimination rate constant): is a value used to describe the rate at which a drug is removed from the human system.

It is equivalent to the fraction of a substance that is removed per unit time measured at any particular instant and has units of 1/h.

Time Frame Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: 1/h
Voriconazole Number Analyzed 5 participants 6 participants 6 participants 6 participants
0.30  (1.52) 0.23  (1.09) 0.22  (1.17) 0.19  (1.22)
N-oxide voriconazole Number Analyzed 6 participants 6 participants 5 participants 6 participants
0.19  (1.08) 0.19  (1.21) 0.20  (1.27) 0.16  (1.26)
6.Secondary Outcome
Title CL/F for Voriconazole - Part 1
Hide Description Apparent clearance: Equal to the drug dose divided by the area-under-the-curve; is an important pharmacokinetic parameter and plays an important role in the selection of a safe and tolerable dose for first-in-human studies.
Time Frame Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: L/h
131.2  (1.04) 124.6  (1.17) 97.7  (1.39) 108.7  (1.22)
7.Secondary Outcome
Title Vz/F for Voriconazole - Part 1
Hide Description Vz/F=Apparent volume of distribution during terminal phase.
Time Frame Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 3 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: liters
614.3  (1.09) 553.1  (1.14) 450.9  (1.25) 569.6  (1.20)
8.Secondary Outcome
Title MR AUC0-t, MR AUC0-inf for N-oxide Voriconazole - Part 1
Hide Description

MR = metabolite ratio. Metabolite ratios (as appropriate) will be calculated for AUC and Cmax parameters.

Area under the serum concentration time curve from time 0 to time t (hours) (AUC0-t)

Time Frame Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
MR AUC0-t Number Analyzed 6 participants 6 participants 6 participants 6 participants
12.25  (1.36) 7.76  (1.40) 4.28  (1.43) 5.59  (1.14)
MR AUC0-inf Number Analyzed 5 participants 6 participants 5 participants 6 participants
10.92  (1.20) 8.18  (1.39) 4.92  (1.42) 6.12  (1.08)
9.Secondary Outcome
Title MR Cmax for N-oxide Voriconazole - Part 1
Hide Description

MR = metabolite ratio. Metabolite ratios (as appropriate) will be calculated for AUC and Cmax parameters.

Cmax is the highest concentration of a drug in the blood, cerebrospinal fluid, or target organ after a dose is given.

Time Frame Part 1: at day 1 (pre-dose, at 1.5h-2h-3h-4h-12h post dose).
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
6.84  (1.27) 5.57  (1.73) 2.73  (1.51) 3.04  (1.31)
10.Secondary Outcome
Title AUC0-t, AUC0-inf for Voriconazole and N-oxide Voriconazole - Part 2
Hide Description AUC0-t = Area under the serum concentration time curve from time 0 to time t (hours) (AUC0-t) (AUC0-24 for Part 2) AUC0-inf = Area under the serum concentration time curve from time 0 to infinity
Time Frame Part 2: Day 1 (1.5, 2, 3, 4, and 12 hours post-0-hour dose) and Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: h*ng/mL
AUC0-t Voriconazole - Day 1 Number Analyzed 6 participants 6 participants 6 participants
69.65  (1.39) 139.29  (1.21) 329.28  (1.19)
AUC0-inf Voriconazole - Day 1 Number Analyzed 5 participants 6 participants 6 participants
78.20  (1.40) 155.72  (1.16) 358.13  (1.20)
AUC0-t Voriconazole - Day 10 Number Analyzed 6 participants 6 participants 6 participants
91.00  (1.36) 256.04  (1.41) 480.22  (1.27)
AUC0-inf Voriconazole - Day 10 Number Analyzed 6 participants 5 participants 6 participants
97.78  (1.35) 258.66  (1.44) 493.04  (1.29)
AUC0-t N-oxide Voriconazole - Day 1 Number Analyzed 6 participants 6 participants 6 participants
391.28  (1.19) 769.65  (1.15) 1990.76  (1.23)
AUC0-inf N-oxide Voriconazole - Day 1 Number Analyzed 6 participants 6 participants 4 participants
439.14  (1.20) 849.27  (1.17) 2001.85  (1.24)
AUC0-t N-oxide Voriconazole - Day 10 Number Analyzed 6 participants 6 participants 6 participants
728.68  (1.31) 1784.63  (1.40) 3353.43  (1.27)
AUC0-inf N-oxide Voriconazole - Day 10 Number Analyzed 6 participants 5 participants 5 participants
752.99  (1.32) 1807.93  (1.47) 3174.66  (1.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for Voriconazole AUC0-t Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 2.00
Confidence Interval (2-Sided) 90%
1.528 to 2.617
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for Voriconazole AUC0-t Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 4.73
Confidence Interval (2-Sided) 90%
3.612 to 6.187
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for Voriconazole AUC0-t day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 2.81
Confidence Interval (2-Sided) 90%
2.017 to 3.925
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for Voriconazole AUC0-t Day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 5.28
Confidence Interval (2-Sided) 90%
3.783 to 7.361
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for N-oxide Voriconazole AUC0-t Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.97
Confidence Interval (2-Sided) 90%
1.615 to 2.396
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for N-oxide Voriconazole AUC0-t Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 5.09
Confidence Interval (2-Sided) 90%
4.178 to 6.196
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for N-oxide Voriconazole AUC0-t Day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 2.45
Confidence Interval (2-Sided) 90%
1.791 to 3.349
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for N-oxide Voriconazole AUC0-t Day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 4.60
Confidence Interval (2-Sided) 90%
3.365 to 6.294
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for Voriconazole AUC0-inf Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.99
Confidence Interval (2-Sided) 90%
1.524 to 2.602
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for Voriconazole AUC0-inf Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 4.58
Confidence Interval (2-Sided) 90%
3.505 to 5.984
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for Voriconazole AUC0-inf Day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 2.65
Confidence Interval (2-Sided) 90%
1.851 to 3.781
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for Voriconazole AUC0-inf Day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 5.04
Confidence Interval (2-Sided) 90%
3.587 to 7.088
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for N-oxide Voriconazole AUC0-inf Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.93
Confidence Interval (2-Sided) 90%
1.569 to 2.384
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for N-oxide Voriconazole AUC0-inf Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 4.56
Confidence Interval (2-Sided) 90%
3.608 to 5.759
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for N-oxide Voriconazole AUC0-inf Day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 2.40
Confidence Interval (2-Sided) 90%
1.694 to 3.402
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for N-oxide Voriconazole AUC0-inf Day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 4.22
Confidence Interval (2-Sided) 90%
2.975 to 5.974
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Cmax for Voriconazole and N-oxide Voriconazole - Part 2
Hide Description Cmax is the highest concentration of a drug in the blood, cerebrospinal fluid, or target organ after a dose is given;
Time Frame Part 2: Day 1 (1.5, 2, 3, 4, and 12 hours post-0-hour dose) and Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Voriconazole - Day 1 19.87  (1.29) 40.42  (1.33) 96.77  (1.16)
Voriconazole - Day 10 21.38  (1.21) 57.11  (1.33) 127.54  (1.20)
N-oxide Voriconazole - Day 1 71.66  (1.24) 144.43  (1.11) 339.11  (1.15)
N-oxide Voriconazole - Day 10 102.78  (1.30) 217.76  (1.23) 412.40  (1.21)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for Voriconazole Cmax Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 2.03
Confidence Interval (2-Sided) 90%
1.562 to 2.650
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for Voriconazole Cmax Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 4.87
Confidence Interval (2-Sided) 90%
3.740 to 6.345
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for Voriconazole Cmax Day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 2.67
Confidence Interval (2-Sided) 90%
2.081 to 3.429
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for Voriconazole Cmax Day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 5.97
Confidence Interval (2-Sided) 90%
4.647 to 7.658
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for N-oxide Voriconazole Cmax Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 2.02
Confidence Interval (2-Sided) 90%
1.688 to 2.406
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for N-oxide Voriconazole Cmax Day 1
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 4.73
Confidence Interval (2-Sided) 90%
3.964 to 5.650
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 20mg Bid
Comments Statistics for N-oxide Voriconazole Cmax Day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 2.12
Confidence Interval (2-Sided) 90%
1.655 to 2.711
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 10mg Bid, Part 2 - ZP-059 40mg qd
Comments Statistics for N-oxide Voriconazole Cmax day 10
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 4.01
Confidence Interval (2-Sided) 90%
3.135 to 5.135
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Tmax and T1/2 for Voriconazole and N-oxide Voriconazole - Part 2
Hide Description Tmax= Time to maximum concentration (Cmax). T 1/2 = Elimination half-life: the time taken for the plasma concentration to fall by half its original value.
Time Frame Part 2: Day 1 (1.5, 2, 3, 4, and 12 hours post-0-hour dose) and Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: hours
Tmax Voriconazole - Day 1 Number Analyzed 6 participants 6 participants 6 participants
1.50  (1.00) 1.50  (1.00) 1.57  (1.11)
Tmax Voriconazole - Day 10 Number Analyzed 6 participants 6 participants 6 participants
1.50  (1.00) 1.50  (1.00) 1.50  (1.00)
Tmax N-oxide Voriconazole - Day 1 Number Analyzed 6 participants 6 participants 6 participants
1.65  (1.15) 1.50  (1.00) 1.65  (1.15)
Tmax N-oxide Voriconazole - Day 10 Number Analyzed 6 participants 6 participants 6 participants
1.57  (1.11) 1.57  (1.11) 2.33  (1.45)
T1/2 Voriconazole - Day 1 Number Analyzed 6 participants 6 participants 6 participants
3.60  (1.36) 3.53  (1.25) 3.24  (1.08)
T1/2 Voriconazole - Day 10 Number Analyzed 6 participants 5 participants 6 participants
4.40  (1.41) 5.15  (1.29) 4.48  (1.15)
T1/2 N-oxide Voriconazole - Day 1 Number Analyzed 6 participants 6 participants 6 participants
3.45  (1.08) 3.20  (1.11) 3.82  (1.44)
T1/2 N-oxide Voriconazole - Day 10 Number Analyzed 6 participants 5 participants 5 participants
4.52  (1.16) 5.04  (1.24) 4.14  (1.21)
13.Secondary Outcome
Title Kel for Voriconazole and N-oxide Voriconazole - Part 2
Hide Description

Kel (Elimination rate constant): is a value used to describe the rate at which a drug is removed from the human system.

It is equivalent to the fraction of a substance that is removed per unit time measured at any particular instant and has units of 1/h.

Time Frame Part 2: Day 1 (1.5, 2, 3, 4, and 12 hours post-0-hour dose) and Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: 1/h
Voriconazole - Day 1 Number Analyzed 6 participants 6 participants 6 participants
0.19  (1.35) 0.20  (1.25) 0.21  (1.08)
Voriconazole - Day 10 Number Analyzed 6 participants 5 participants 6 participants
0.16  (1.41) 0.13  (1.29) 0.15  (1.15)
N-oxide Voriconazole - Day 1 Number Analyzed 6 participants 6 participants 6 participants
0.20  (1.08) 0.22  (1.11) 0.18  (1.44)
N-oxide Voriconazole - Day 10 Number Analyzed 6 participants 5 participants 5 participants
0.15  (1.16) 0.14  (1.24) 0.17  (1.21)
14.Secondary Outcome
Title CL/F for Voriconazole - Part 2
Hide Description Apparent clearance: Equal to the drug dose divided by the area-under-the-curve; is an important pharmacokinetic parameter and plays an important role in the selection of a safe and tolerable dose for first-in-human studies.
Time Frame Part 2: Only at Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: L/h
120.9  (1.29) 93.1  (1.32) 93.5  (1.25)
15.Secondary Outcome
Title Swing for Voriconazole and N-oxide Voriconazole - Part 2
Hide Description Swing for voriconazole and N-oxide voriconazole = [(Cmax - Cmin) / Cmin]*100%
Time Frame Part 2: Only at Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: percentage concentration
Voriconazole 10.50  (1.48) 9.62  (1.68) 55.16  (1.63)
N-oxide Voriconazole 4.60  (1.16) 3.81  (1.48) 20.65  (2.70)
16.Secondary Outcome
Title AUCtau for Voriconazole and N-oxide Voriconazole - Part 2
Hide Description Area under the serum concentration time curve for the dosing interval
Time Frame Part 2: Only at Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: h*ng/mL
Voriconazole 82.82  (1.30) 215.56  (1.32) 427.57  (1.25)
N-oxide Voriconazole 620.89  (1.28) 1438.74  (1.31) 2803.51  (1.20)
17.Secondary Outcome
Title Css,av for Voriconazole and N-oxide Voriconazole - Part 2
Hide Description Css,av or Css(ave): Average drug concentration at steady state; Steady-state concentration (Css) occurs when the amount of a drug being absorbed is the same amount that's being cleared from the body when the drug is given continuously or repeatedly
Time Frame Part 2: Only at Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Voriconazole 6.91  (1.30) 17.95  (1.32) 35.64  (1.25)
N-oxide Voriconazole 51.75  (1.28) 119.88  (1.31) 233.63  (1.20)
18.Secondary Outcome
Title Fluctuation for Voriconazole and N-oxide Voriconazole - Part 2
Hide Description Peak trough fluctuation in serum concentrations within one dosing interval at steady state. Fluctuation - Over the Dosing Interval - is expressed as percentage concentration.
Time Frame Part 2: Only at Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: percentage concentration
Voriconazole 281.0  (1.15) 284.9  (1.24) 350.8  (1.10)
N-oxide Voriconazole 162.8  (1.08) 141.8  (1.21) 163.8  (1.30)
19.Secondary Outcome
Title Rac for Voriconazole and N-oxide Voriconazole - Part 2
Hide Description Accumulation ratio. The drug accumulation ratio (Rac) is the ratio of accumulation of a drug under steady state conditions as compared to a single dose. The higher the value, the more the drug accumulates in the body. An Rac of 1 means no accumulation.
Time Frame Part 2: Only at Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
Voriconazole 1.19  (1.17) 1.55  (1.29) 1.30  (1.27)
N-oxide Voriconazole 1.59  (1.11) 1.87  (1.20) 1.41  (1.10)
20.Secondary Outcome
Title Rlinear for Voriconazole and N-oxide Voriconazole - Part 2
Hide Description Rlinear means linearity ratio for Area Under the Serum Concentration-Time Curve from time zero to infinity.
Time Frame Part 2: Only at Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
Voriconazole Number Analyzed 5 participants 6 participants 6 participants
1.06  (1.14) 1.38  (1.25) 1.19  (1.26)
N-oxide Voriconazole Number Analyzed 6 participants 5 participants 4 participants
1.42  (1.12) 1.70  (1.21) 1.30  (1.17)
21.Secondary Outcome
Title MR AUC0-t, MR AUC0-inf and MR AUCtau for N-oxide Voriconazole - Part 2
Hide Description

MR = metabolite ratio. Metabolite ratios (as appropriate) will be calculated for AUC and Cmax parameters.

Area under the serum concentration time curve from time 0 to time t (hours) (AUC0-t)

Time Frame Part 2: Day 1 (1.5, 2, 3, 4, and 12 hours post-0-hour dose) and Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
MR AUC0-t N-oxide Voriconazole - Day 1 Number Analyzed 6 participants 6 participants 6 participants
5.62  (1.50) 5.53  (1.32) 6.04  (1.27)
MR AUC0-inf N-oxide Voriconazole - Day 1 Number Analyzed 5 participants 6 participants 4 participants
5.68  (1.52) 5.45  (1.29) 5.55  (1.20)
MR AUC0-t N-oxide Voriconazole - Day 10 Number Analyzed 6 participants 6 participants 6 participants
8.01  (1.40) 6.97  (1.32) 6.98  (1.16)
MR AUC0-inf N-oxide Voriconazole - Day 10 Number Analyzed 6 participants 5 participants 5 participants
7.70  (1.40) 6.99  (1.34) 7.11  (1.18)
MR AUCtau N-oxide Voriconazole - Day 10 Number Analyzed 6 participants 6 participants 6 participants
7.50  (1.39) 6.68  (1.30) 6.56  (1.20)
22.Secondary Outcome
Title MR Cmax N-oxide Voriconazole - Part 2
Hide Description

MR = metabolite ratio. Metabolite ratios (as appropriate) will be calculated for AUC and Cmax parameters.

Cmax is the highest concentration of a drug in the blood, cerebrospinal fluid, or target organ after a dose is given.

Time Frame Part 2: Day 1 (1.5, 2, 3, 4, and 12 hours post-0-hour dose) and Day 10 (post-0-hour dose at 1.5, 2, 3, 4, and 12 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
N-oxide Voriconazole - Day 1 3.61  (1.50) 3.57  (1.40) 3.50  (1.22)
N-oxide Voriconazole - Day 10 4.81  (1.38) 3.81  (1.34) 3.23  (1.37)
23.Secondary Outcome
Title Cmax for Voriconazole and N-oxide Voriconazole - Part 3
Hide Description Cmax is the highest concentration of a drug in the blood, cerebrospinal fluid, or target organ after a dose is given;
Time Frame Day 1 of the respective treatment period 1 or 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 3 - ZP-059 Part 3 - Oral Voriconazole
Hide Arm/Group Description:

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 16 16
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Voriconazole 108.08  (1.42) 863.22  (1.44)
N-oxide Voriconazole 151.43  (1.25) 1589.05  (1.25)
24.Secondary Outcome
Title Vz/F for Voriconazole - Part 3
Hide Description Vz/F=Apparent volume of distribution during terminal phase.
Time Frame Only at Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd
Hide Arm/Group Description:

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 3: 40mg (8 x 5 mg capsule) ZP-059 once daily (qd) d) administered via DPI (RS01 monodose device) on Days 1 to 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Overall Number of Participants Analyzed 6 5 6
Geometric Mean (Standard Deviation)
Unit of Measure: Liters
767.1  (1.47) 714.3  (1.25) 604.9  (1.13)
25.Secondary Outcome
Title AUC0-t, AUC0-inf for Voriconazole and N-oxide Voriconazole - Part 3
Hide Description AUC0-t = Area under the serum concentration time curve from time 0 to time t (hours) (AUC0-t) (AUC0-96 for Part 3) AUC0-inf = Area under the serum concentration time curve from time 0 to infinity
Time Frame Day 1 of the respective treatment period 1 or 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 3 - ZP-059 Part 3 - Oral Voriconazole
Hide Arm/Group Description:

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 16 16
Geometric Mean (Standard Deviation)
Unit of Measure: h*ng/mL
AUC0-t Voriconazole Number Analyzed 16 participants 16 participants
290.02  (1.87) 3726.68  (1.91)
AUC0-inf Voriconazole Number Analyzed 15 participants 16 participants
269.61  (1.56) 3800.41  (1.92)
AUC0-t N-oxide Voriconazole Number Analyzed 16 participants 16 participants
1128.69  (1.27) 21504.52  (1.20)
AUC0-inf N-oxide Voriconazole Number Analyzed 16 participants 16 participants
1154.35  (1.26) 21788.46  (1.20)
26.Secondary Outcome
Title Tmax and T1/2 for Voriconazole and N-oxide Voriconazole - Part 3
Hide Description Tmax= Time to maximum concentration (Cmax). T 1/2 = Elimination half-life: the time taken for the plasma concentration to fall by half its original value.
Time Frame Day 1 of the respective treatment period 1 or 2 (Pre-dose, 0.25h, 0.75h 1.5h, 2h ,3h ,4h ,6h ,8h ,12h ,16h , 24h ,48h after dosing)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 3 - ZP-059 Part 3 - Oral Voriconazole
Hide Arm/Group Description:

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 16 16
Geometric Mean (Standard Deviation)
Unit of Measure: hours
Tmax Voriconazole Number Analyzed 16 participants 16 participants
0.43  (3.64) 1.16  (1.40)
Tmax N-oxide Voriconazole Number Analyzed 16 participants 16 participants
1.74  (1.31) 2.76  (1.52)
T1/2 Voriconazole Number Analyzed 15 participants 16 participants
5.13  (1.27) 6.93  (1.32)
T1/2 N-oxide Voriconazole Number Analyzed 16 participants 16 participants
4.68  (1.19) 6.42  (1.35)
27.Secondary Outcome
Title CL/F for Voriconazole - Part 3
Hide Description Apparent clearance: Equal to the drug dose divided by the area-under-the-curve; is an important pharmacokinetic parameter and plays an important role in the selection of a safe and tolerable dose for first-in-human studies.
Time Frame Day 1 of the respective treatment period 1 or 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 3 - ZP-059 Part 3 - Oral Voriconazole
Hide Arm/Group Description:

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 15 16
Geometric Mean (Standard Deviation)
Unit of Measure: L/h
74.2  (1.57) 52.4  (1.93)
28.Secondary Outcome
Title Kel for Voriconazole and N-oxide Voriconazole - Part 3
Hide Description

Kel (Elimination rate constant): is a value used to describe the rate at which a drug is removed from the human system.

It is equivalent to the fraction of a substance that is removed per unit time measured at any particular instant and has units of 1/h.

Time Frame Day 1 of the respective treatment period 1 or 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 3 - ZP-059 Part 3 - Oral Voriconazole
Hide Arm/Group Description:

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 16 16
Geometric Mean (Standard Deviation)
Unit of Measure: 1/h
Voriconazole Number Analyzed 15 participants 16 participants
0.14  (1.26) 0.10  (1.31)
N-oxide Voriconazole Number Analyzed 16 participants 16 participants
0.15  (1.19) 0.11  (1.34)
29.Secondary Outcome
Title Vz/F for Voriconazole - Part 3
Hide Description Vz/F=Apparent volume of distribution during terminal phase.
Time Frame Day 1 of the respective treatment period 1 or 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 3 - ZP-059 Part 3 - Oral Voriconazole
Hide Arm/Group Description:

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 15 16
Geometric Mean (Standard Deviation)
Unit of Measure: Liters
549.0  (1.46) 526.0  (1.69)
30.Secondary Outcome
Title MR AUC0-t and MR AUC0-inf for N-oxide Voriconazole - Part 3
Hide Description

MR = metabolite ratio. Metabolite ratios (as appropriate) will be calculated for AUC and Cmax parameters.

Area under the serum concentration time curve from time 0 to time t (hours) (AUC0-t)

Time Frame Day 1 of the respective treatment period 1 or 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 3 - ZP-059 Part 3 - Oral Voriconazole
Hide Arm/Group Description:

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 16 16
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
MR AUC0-t Number Analyzed 16 participants 16 participants
3.89  (1.92) 5.77  (1.81)
MR AUC0-inf Number Analyzed 15 participants 16 participants
4.38  (1.48) 5.74  (1.79)
31.Secondary Outcome
Title MR Cmax for N-oxide Voriconazole - Part 3
Hide Description

MR = metabolite ratio. Metabolite ratios (as appropriate) will be calculated for AUC and Cmax parameters.

Cmax is the highest concentration of a drug in the blood, cerebrospinal fluid, or target organ after a dose is given.

Time Frame Day 1 of the respective treatment period 1 or 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 3 - ZP-059 Part 3 - Oral Voriconazole
Hide Arm/Group Description:

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 16 16
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
1.40  (1.44) 1.84  (1.54)
32.Secondary Outcome
Title Bioavailability of Voriconazole - Cmax
Hide Description

The Cmax estimated from Part 3 was analyzed to assess the relative bioavailability of inhaled ZP-059 to oral voriconazole.

The Cmax was compared between asthma subjects in Part 3 and healthy subjects in Part 1 and separately with asthma subjects in Part 2 to assess the relative bioavailability of ZP-059 dose taken in Part 3 in these populations.

In Part 1 and 3, Cmax was estimated only on Day1. In Part 2, Cmax was estimated on Day 10.

Time Frame On Day 1 in Parts 1-3 and on Day 10 in Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 20mg Part 2 - ZP-059 20mg Bid Part 3 - ZP-059 Part 3 - Oral Voriconazole
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 6 6 16 16
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Parts 1, 2, and 3 - Day 1 Number Analyzed 6 participants 6 participants 16 participants 16 participants
53.37  (1.32) 40.42  (1.33) 108.08  (1.42) 863.22  (1.44)
Part 2 - Day 10 Number Analyzed 0 participants 6 participants 0 participants 0 participants
57.11  (1.33)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 3 - ZP-059, Part 3 - Oral Voriconazole
Comments Part 3 - ZP-059 20mg: Oral Voriconazole (200mg VFEND)
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.13
Confidence Interval (2-Sided) 90%
0.107 to 0.146
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 20mg, Part 3 - ZP-059
Comments ZP-059 20mg: Part 3 / Part 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 2.10
Confidence Interval (2-Sided) 90%
1.545 to 2.853
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 20mg Bid, Part 3 - ZP-059
Comments ZP-059 20mg: Part 3 / Part 2 Day 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 2.63
Confidence Interval (2-Sided) 90%
1.953 to 3.544
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 20mg Bid, Part 3 - ZP-059
Comments ZP-059 20mg: Part 3 / Part 2 Day 10
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.87
Confidence Interval (2-Sided) 90%
1.386 to 2.520
Estimation Comments [Not Specified]
33.Secondary Outcome
Title Bioavailability of Voriconazole - AUC-inf
Hide Description

The AUC0-inf estimated from Part 3 was analyzed to assess the relative bioavailability of inhaled ZP-059 to oral voriconazole.

The AUC0-inf was compared between asthma subjects in Part 3 and healthy subjects in Part 1 and separately with asthma subjects in Part 2 to assess the relative bioavailability of ZP-059 dose taken in Part 3 in these populations.

In Part 1 and 3, AUC0-inf was estimated on Day 1. In part 2, AUC0-in f was estimated on Day 10.

Time Frame On Day 1 in Parts 1-3 and on Day 10 in Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Concentration Set: SAF subjects who had at least 1 quantifiable serum PK concentration recorded, analyzed according to the treatment actually taken.
Arm/Group Title Part 1 - ZP-059 20mg Part 2 - ZP-059 20mg Bid Part 3 - ZP-059 Part 3 - Oral Voriconazole
Hide Arm/Group Description:

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Crossover treatment period: Single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI, and a single dose of oral voriconazole (200 mg Vfend® tablet) on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Crossover treatment period: Single dose of oral voriconazole (200 mg Vfend® tablet), and a single inhaled dose (20 mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 of the respective treatment period with a washout period of at least 96 hours.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

oral voriconazole: Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Overall Number of Participants Analyzed 6 6 16 16
Geometric Mean (Standard Deviation)
Unit of Measure: h*ng/mL
Parts 1, 2, and 3 - Day 1 Number Analyzed 6 participants 6 participants 16 participants 16 participants
203.96  (1.44) 155.72  (1.16) 269.61  (1.56) 3800.41  (1.92)
Part 2 - Day 10 Number Analyzed 0 participants 6 participants 0 participants 0 participants
258.66  (1.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 3 - ZP-059, Part 3 - Oral Voriconazole
Comments Part 3 ZP-059 20mg: Oral Voriconazole (200mg VFEND®)
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.07
Confidence Interval (2-Sided) 90%
0.059 to 0.075
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1 - ZP-059 20mg, Part 3 - ZP-059
Comments ZP-059 20mg: Part 3 / Part 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.27
Confidence Interval (2-Sided) 90%
0.850 to 1.891
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 20mg Bid, Part 3 - ZP-059
Comments ZP-059 20mg: Part 3 / Part 2 Day 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 2.63
Confidence Interval (2-Sided) 90%
1.953 to 3.544
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 - ZP-059 20mg Bid, Part 3 - ZP-059
Comments ZP-059 20mg: Part 3 / Part 2 Day 10
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.87
Confidence Interval (2-Sided) 90%
1.386 to 2.520
Estimation Comments [Not Specified]
Time Frame Throughout Part 1 (Day 1, Day 2, Day 3 by phone, Day 5 on return visit) until Days 9-13 by follow-up phone calls. Throughout Part 2 from Day 1 to Day 11, on Day 14 and Day 17 on return visits until Days 11-17 after the last dose by follow-up phone calls. Throughout Part 3 from Day 1 until Day 4
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1 - ZP-059 5mg Part 1 - ZP-059 10mg Part 1 - ZP-059 20mg Part 1 - ZP-059 40mg Part 2 - ZP-059 10mg Bid Part 2 - ZP-059 20mg Bid Part 2 - ZP-059 40mg qd Part 3 - ZP-059 Part 3 - Oral Voriconazole
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Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 1: 5mg (1 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 2: 10mg (2 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 3: 20mg (4 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 1: administration of single ascending doses (SAD) of ZP-059.

Cohort 4: 40mg (8 x 5 mg capsule) ZP-059 single dose administered via DPI (RS01 monodose device) on Day 1.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Days 1 to 10.

Cohort 1: 10mg (2 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10.

Part 3 (2-period crossover): eligible subjects received a single inhaled dose (20mg) of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study.

ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).

Part 2: administration of multiple ascending doses (MAD) of ZP-059 on Day 1 to 10.

Cohort 2: 20mg (4 x 5 mg capsule) ZP-059 twice daily (bid) administered via DPI (RS01 monodose device) for 9 days and once in the morning of Day 10.

Voriconazole inhaled: Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1.

Part 2 (MAD): eligible subjects received 2 (10mg twice daily [BID]) or 4 [20mg BID]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily [QD]) for 10 da