Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis

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: NCT03960606
Recruitment Status : Terminated (COVID-19 Pandemic)
First Posted : May 23, 2019
Last Update Posted : July 16, 2020
Sponsor:
Information provided by (Responsible Party):
Pulmatrix Inc.

Brief Summary:
A Randomized, Double-Blind, Multicenter, Placebo-Controlled, Phase 2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Itraconazole Administered as a Dry Powder for Inhalation (PUR1900) in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis

Condition or disease Intervention/treatment Phase
Asthma Combination Product: PUR1900 Phase 2

Detailed Description:

This is a randomized, double-blind, multicenter, placebo controlled, multiple-arm study.

Following screening and confirmation of eligibility, subjects will be randomly assigned (1:1:1:1) into 4 arms of 16 subjects each and will receive 10 mg, 20 mg, or 35 mg of PUR1900 or placebo, administered via dry powder inhalation daily for 28 days. The doses of PUR1900 are stated in this protocol as the respective nominal doses of itraconazole.

Subject eligibility for the study will be determined within 28 days before the first dose of study drug (Day 1) and will be confirmed between 9 and 6 days before dosing and again on Day 1.

Eligible subjects will begin daily dosing with study drug (PUR1900 or placebo) on Day 1.

Subjects will return to the study site for visits on Days 2, 7, 14, and 28 and will be dosed at the study site. The remaining daily doses of study drug will be self-administered at home.

A follow-up visit will occur 7 to 10 days after the last dose of study drug.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Following screening and confirmation of eligibility, subjects will be randomly assigned (1:1:1:1) into 4 arms of 16 subjects each and will receive 10 mg, 20 mg, or 35 mg of PUR1900 or placebo, administered via dry powder inhalation daily for 28 days.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: The study will be performed in a double-blind manner. All study drug will be supplied in identical packaging and will be similar in color, smell, taste, and appearance to enable double-blind conditions. All study personnel will remain blinded until after database lock, unless the nature of their activities in the study specifically requires them to be unblinded. Any study documents, supplies, and tools will be reviewed to identify components that have the potential to unblind the study, and blinding restrictions will be applied where appropriate.
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety, Tolerability, & Pharmacokinetics of Itraconazole Administered as a Dry Powder for Inhalation (PUR1900) in Asthmatic Patients With ABPA
Actual Study Start Date : July 31, 2019
Actual Primary Completion Date : July 14, 2020
Actual Study Completion Date : July 14, 2020


Arm Intervention/treatment
Experimental: 10 mg PUR1900
Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)
Combination Product: PUR1900
PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.

Experimental: 20 mg PUR1900
Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)
Combination Product: PUR1900
PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.

Experimental: 35 mg PUR1900
Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)
Combination Product: PUR1900
PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.

Placebo Comparator: Placebo
Placebo will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)
Combination Product: PUR1900
PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
  2. Incidence of intraday FEV1 declines [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
  3. Respiratory rate [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
  4. Blood pressure [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    Systolic pressure over diastolic pressure

  5. Heart rate [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    Beats per minute

  6. Oxygen saturation [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    As a percentage

  7. Physical examination findings [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    Physician's notes

  8. Clinical laboratory test results [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    Lab reports with any out of range results flagged

  9. 12-Lead electrocardiogram findings [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    ECG report and tracing


Secondary Outcome Measures :
  1. Sputum concentrations of itraconazole and hydroxy-itraconazole [ Time Frame: Day 2 to Day 28 ]
  2. Sputum eosinophils [ Time Frame: (Day -9 to Day -6) to Day 28 ]
  3. To evaluate the effect of PUR1900 on pulmonary function following single- and multiple-dose administration of PUR1900 [ Time Frame: Day 1 to Day 28 ]
  4. Asthma Control Questionnaire-6 (ACQ 6) [ Time Frame: Day 1 to Day 28 ]
    Scores range between 0 (totally controlled) and 6 (severely uncontrolled).

  5. Change from baseline (Day 1) to Day 28 in A fumigatus burden in sputum [ Time Frame: Day 1 to Day 28 ]
    As assessed by quantitative PCR and sputum culture

  6. Cmax (maximum observed concentration in plasma) [ Time Frame: Day 1 to Day 28 ]
  7. Tmax (time to maximum concentration in plasma) [ Time Frame: Day 1 to Day 28 ]
  8. AUC (area under the concentration-time curve) [ Time Frame: Day 1 to Day 28 ]
  9. CL/F (clearance) [ Time Frame: Day 1 to Day 28 ]
  10. Vz/F (apparent volume of distribution) [ Time Frame: Day 1 to Day 28 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is a male or female, 18 to 75 years old (inclusive) at the time of signing the informed consent.
  • Has a body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening.
  • Has a historical diagnosis of asthma, as per the Global Initiative for Asthma (GINA) 2018 update.
  • Has a confirmed historical diagnosis of ABPA, as per the Modified International Society for Human and Animal Mycology (ISHAM) working group 2013 criteria.
  • Is currently considered to be in one of the following stages of ABPA: Stage 2 (Response), Stage 4 (Remission), Stage 5a (Treatment-dependent ABPA), or Stage 5b (Glucocorticoid-dependent asthma)
  • Has a serum immunoglobulin (Ig) E ≥1000 IU/mL during screening (Visit 1 or Visit 2).
  • Can perform a valid, reproducible spirometry test with demonstration of a prebronchodilator FEV1 ≥50% of predicted normal for age, sex, race, and height (Quanjer et al 2012) at a screening visit.
  • Has a documented stable asthma medication regimen during screening (Day 28 to Day 1), including SABA, LABA, and LTRA use and inhaled and/or oral GCS.
  • Subjects who are sexually active, male subjects able to father a child, and female subjects of childbearing potential must agree to follow the contraception requirements of this protocol.
  • Can demonstrate the correct inhalation technique for the use of the delivery device at screening and before dosing.

Exclusion Criteria:

  • Is a female of childbearing potential who is pregnant or lactating or who plans to become pregnant during the study. A woman is considered to be of childbearing potential unless she is either permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or postmenopausal (had no menses for 12 months without an alternative medical cause).
  • Has a history of life-threatening asthma within the last 5 years, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, and/or hypoxic seizures.
  • Had an occurrence of asthma or ABPA exacerbations within the 28 days before screening or during the 28-day period before Day 1.
  • Had an occurrence of clinically significant bacterial, viral, or fungal infection that required systemic (oral or intravenous) antibiotics, antivirals, or antifungals within the 28 days before screening. Topical treatments, other than antifungals, are allowed.
  • Received any investigational medical product in a clinical research study within the previous 3 months before dosing in this study.
  • Has previously received PUR1900.
  • Has a history of any significant drug or alcohol abuse in the past 2 years before screening, as judged by the investigator.
  • Has current tobacco or inhaled marijuana use or history of smoking tobacco or marijuana within the last 6 months before screening.
  • Is a current user of e-cigarettes or has used these products within the last 6 months before screening.
  • Has a positive urine test result for drugs of abuse, alcohol, or cotinine at screening
  • Has a history of allergies to or hypersensitivity reactions after dosing of itraconazole or other antifungal azoles.
  • Had a major trauma or surgery within the last 28 days before screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03960606


Locations
Show Show 20 study locations
Sponsors and Collaborators
Pulmatrix Inc.
Investigators
Layout table for investigator information
Principal Investigator: William J. Calhoun, MD University of Texas Medical Branch Galveston, TX 77555
Principal Investigator: David Denning, FRCP, FRC Path, FIDSA, FMedSci Director, National Aspergillosis Centre Manchester, Wythenshawe M23 9LT, UK
Layout table for additonal information
Responsible Party: Pulmatrix Inc.
ClinicalTrials.gov Identifier: NCT03960606    
Other Study ID Numbers: 601-0014
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: July 16, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pulmatrix Inc.:
Aspergillosis
Additional relevant MeSH terms:
Layout table for MeSH terms
Aspergillosis
Mycoses