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Safety, Tolerability and Pharmacokinetics of PUR1900 (Itraconazole Powder) in Healthy Volunteers and Adults With Asthma

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ClinicalTrials.gov Identifier: NCT03479411
Recruitment Status : Completed
First Posted : March 27, 2018
Last Update Posted : July 27, 2018
Sponsor:
Information provided by (Responsible Party):
Pulmatrix Inc.

Brief Summary:
Phase 1, 3-part study to assess safety, tolerability and PK of single and multiple doses of itraconazole administered as a dry powder for inhalation (PUR1900) in healthy subjects (parts 1 and 2) and a 2-period crossover study of single doses of itraconazole administered as a dry powder for inhalation (PUR1900) and an oral solution (Sporanox) in adults with mild to moderate, stable asthma (part 3)

Condition or disease Intervention/treatment Phase
Asthma Drug: Itraconazole Powder Drug: Itraconazole 200 mg Phase 1

Detailed Description:

Phase 1, multi-center, 3-part, open-label study in healthy adults (Parts 1 and 2) and adults with mild to moderate, stable asthma (Part 3).

Safety, tolerability and PK will be assessed following either single ascending (SAD) or multiple ascending (MAD) dosing of itraconazole administered as a dry powder for inhalation (PUR1900; Part 1 and Part 2, respectively). Part 1 will comprise 3 separate cohorts planned to receive single doses of 5, 10 and 25 mg itraconzaole, respectively. The study will have an interleaved design; Part 2 will comprise 2 separate cohorts planned to receive daily doses of itraconazole 10 and 20 mg per day for 14 days, respectively. Part 2, Cohort 1 will commence after a review of safety data from Part 1 Cohort 2 suggests it is safe to do so.

Part 3 is a 2-period, randomised, crossover study in adult subjects with mild to moderate stable asthma to assess the safety, tolerability and PK of single doses of itraconazole administered as a dry powder for inhalation (PUR1900) and administered as an oral solution (Sporanox® Oral Solution).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: The study has 3 parts: 1) Single Ascending Dose Escalation and 2) Multiple Ascending Dose Escalation to be conducted in Normal Healthy Volunteers and 3) A two-period crossover study of single doses of PUR1900 and Sporanox in Adults with Asthma
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1, 3-Part, Open-Label Study to Assess Safety, Tolerability and PK of Single and Multiple Doses of PUR1900 in Healthy Subjects and Crossover Study of Single Doses of PUR1900 and Sporanox in Adult Subjects With Mild to Moderate Asthma
Actual Study Start Date : February 9, 2018
Actual Primary Completion Date : June 28, 2018
Actual Study Completion Date : June 28, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Part 1 single ascending dose
Intervention: drug Itraconzaole powder: single dose of 5mg, 10mg or 25 mg Other name: PUR1900
Drug: Itraconazole Powder
Itraconazole administered as a dry powder for inhalation (PUR1900)
Other Name: PUR1900

Experimental: Part 2 multiple ascending dose
Intervention: drug Itraconzaole powder: 10 mg or 20 mg daily for 14 days Other name: PUR1900
Drug: Itraconazole Powder
Itraconazole administered as a dry powder for inhalation (PUR1900)
Other Name: PUR1900

Active Comparator: Part 3 2-period crossover single dose
Intervention: drug Itraconzaole powder: 20 mg single dose and Itraconzaole oral solution 200 mg single dose Other names: PUR1900, Sporanox
Drug: Itraconazole Powder
Itraconazole administered as a dry powder for inhalation (PUR1900)
Other Name: PUR1900

Drug: Itraconazole 200 mg
Sporanox® Oral Solution
Other Name: Sporanox®




Primary Outcome Measures :
  1. Number of participants with treatment-related Adverse Events as assessed by CTCAE v4.0 [ Time Frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28 ]
    Safety and tolerability will be assessed by evaluating the number of participants with treatment-related adverse events as assessed by CTCAE v4.0


Secondary Outcome Measures :
  1. Area under the serum concentration vs time curve from time 0 to infinity (AUC0-inf) of single dose of itraconazole [ Time Frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28 ]
    The area under the serum concentration vs time curve from time 0 to infinity (AUC0-inf)

  2. Time of the maximum measured serum concentration (Tmax) of single dose of itraconazole [ Time Frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28 ]
    Time of the maximum measured serum concentration (Tmax)

  3. Area under the serum concentration vs time curve within the dosing interval (AUCtau) of single dose of itraconazole [ Time Frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28 ]
    The area under the serum concentration vs time curve within the dosing interval (AUCtau)

  4. Apparent first-order terminal elimination half-life (t1/2 ) of single dose of itraconazole [ Time Frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28 ]
    Apparent first-order terminal elimination half-life (t1/2 )

  5. Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the serum concentration vs time curve (Kel) of single dose of itraconazole [ Time Frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28 ]
    Apparent first-order terminal elimination rate constant calculated from a semi-log plot of

  6. Apparent clearance (CL/F) of single dose of itraconazole [ Time Frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28 ]
    Apparent clearance (CL/F)

  7. Apparent volume of distribution (Vz/F) of single dose of itraconazole [ Time Frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28 ]
    Apparent volume of distribution (Vz/F)


Other Outcome Measures:
  1. Maximum Concentration [Cmax] of itraconazole and hydroxyitraconazole in sputum [ Time Frame: Part 3: baseline through 28 days ]
    Exploratory objective: To characterize the concentrations of itraconazole in induced sputum after single doses of inhaled PUR1900 and oral Sporanox® solution in subjects with mild to moderate stable asthma

  2. Area under the Curve [AUC] of itraconazole and hydroxyitraconazole in sputum [ Time Frame: Part 3: baseline through 28 days ]
    Exploratory objective: To characterize the concentrations of itraconazole in induced sputum after single doses of inhaled PUR1900 and oral Sporanox® solution in subjects with mild to moderate stable asthma



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Part 1 (SAD) and Part 2 (MAD):

  1. Healthy males or non-pregnant, non-lactating healthy females.
  2. Age 18 to 60 years
  3. Screening forced expiratory volume in 1 sec (FEV1) ≥80% of the predicted value
  4. Screening FEV1/forced vital capacity (FVC) >0.70.
  5. Able to demonstrate the correct inhalation technique for use of delivery device during the study.

Part 3 (Asthmatic Subjects):

  1. Males or non-pregnant, non-lactating females with a physician-confirmed diagnosis of asthma for at least 3 months. Asthma must be assessed by investigator as being stable for at least 4 weeks prior to screening.
  2. Age 18 to 60 years
  3. Subject is being treated with either inhaled corticosteroids (ICS) or inhaled corticosteroids plus long-acting beta-agonists (ICS/LABA). Only GINA STEP 2 and 3 patients will be enrolled.
  4. Pre-bronchodilator, clinic measured, FEV1 ≥70% of predicted normal at screening
  5. Able to perform the required spirometric testing.
  6. Able to produce a sputum sample of a quality required for drug concentration assessments (a single repeat is permitted).

Exclusion Criteria:

  1. Subjects who have received any IMP in a clinical research study within the previous 3 months prior to dosing on this study
  2. Subjects who have previously received IMP in this study. Subjects who have participated in Part 1 are not permitted to participate in Part 2 or Part 3.
  3. History of any drug or alcohol abuse in the past 2 years prior to screening.
  4. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
  5. Females of childbearing potential who are pregnant or lactating, or who plan to become pregnant during the study (all female subjects must have a negative pregnancy test at screening). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or is postmenopausal (had no menses for 12 months without an alternative medical cause (will be re-assessed at admission/pre-dose).
  6. Positive drugs of abuse test result at screening or admission
  7. Subjects with congestive heart failure or a history of congestive heart failure
  8. History of severe cough or bronchospasm upon inhalation of any dry powder inhalation product
  9. Subjects who are taking or have taken any herbal remedies or CYP3A4 inducers in the 28 days prior to the first IMP administration
  10. Upper respiratory tract infection (excluding otitis media), fever, acute or chronic cough within 14 days of the first IMP administration, or lower respiratory tract infection within the last 3 months prior to IMP administration
  11. Recent (last 4 weeks prior to IMP administration) clinically significant bacterial, viral or fungal infection that required systemic (oral or intravenous) antibiotics, antivirals or antifungals; topical treatments, other than antifungals, are allowed.

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): NCT03479411


Locations
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United Kingdom
Medicines Evaluation Unit
Manchester, United Kingdom
Quotient Sciences
Nottingham, United Kingdom
Sponsors and Collaborators
Pulmatrix Inc.
Investigators
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Study Director: James Roach, MD Pulmatrix Inc.

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Responsible Party: Pulmatrix Inc.
ClinicalTrials.gov Identifier: NCT03479411     History of Changes
Other Study ID Numbers: 601-0013
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: July 27, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Itraconazole
Hydroxyitraconazole
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors