- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03479411
Safety, Tolerability and Pharmacokinetics of PUR1900 (Itraconazole Powder) in Healthy Volunteers and Adults With Asthma
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
Study Overview
Status
Conditions
Intervention / Treatment
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).
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Manchester, United Kingdom
- Medicines Evaluation Unit
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Nottingham, United Kingdom
- Quotient Sciences
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Part 1 (SAD) and Part 2 (MAD):
- Healthy males or non-pregnant, non-lactating healthy females.
- Age 18 to 60 years
- Screening forced expiratory volume in 1 sec (FEV1) ≥80% of the predicted value
- Screening FEV1/forced vital capacity (FVC) >0.70.
- Able to demonstrate the correct inhalation technique for use of delivery device during the study.
Part 3 (Asthmatic Subjects):
- 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.
- Age 18 to 60 years
- 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.
- Pre-bronchodilator, clinic measured, FEV1 ≥70% of predicted normal at screening
- Able to perform the required spirometric testing.
- Able to produce a sputum sample of a quality required for drug concentration assessments (a single repeat is permitted).
Exclusion Criteria:
- Subjects who have received any IMP in a clinical research study within the previous 3 months prior to dosing on this study
- 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.
- History of any drug or alcohol abuse in the past 2 years prior to screening.
- Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
- 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).
- Positive drugs of abuse test result at screening or admission
- Subjects with congestive heart failure or a history of congestive heart failure
- History of severe cough or bronchospasm upon inhalation of any dry powder inhalation product
- Subjects who are taking or have taken any herbal remedies or CYP3A4 inducers in the 28 days prior to the first IMP administration
- 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
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Part 1 single ascending dose
Intervention: drug Itraconzaole powder: single dose of 5mg, 10mg or 25 mg Other name: PUR1900
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Itraconazole administered as a dry powder for inhalation (PUR1900)
Other Names:
|
EXPERIMENTAL: Part 2 multiple ascending dose
Intervention: drug Itraconzaole powder: 10 mg or 20 mg daily for 14 days Other name: PUR1900
|
Itraconazole administered as a dry powder for inhalation (PUR1900)
Other Names:
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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
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Itraconazole administered as a dry powder for inhalation (PUR1900)
Other Names:
Sporanox® Oral Solution
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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Safety and tolerability will be assessed by evaluating the number of participants with treatment-related adverse events as assessed by CTCAE v4.0
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Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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The area under the serum concentration vs time curve from time 0 to infinity (AUC0-inf)
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Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
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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
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Time of the maximum measured serum concentration (Tmax)
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Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
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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
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The area under the serum concentration vs time curve within the dosing interval (AUCtau)
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Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
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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
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Apparent first-order terminal elimination half-life (t1/2 )
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Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
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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
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Apparent first-order terminal elimination rate constant calculated from a semi-log plot of
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Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
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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
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Apparent clearance (CL/F)
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Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
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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
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Apparent volume of distribution (Vz/F)
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Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Concentration [Cmax] of itraconazole and hydroxyitraconazole in sputum
Time Frame: Part 3: baseline through 28 days
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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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Part 3: baseline through 28 days
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Area under the Curve [AUC] of itraconazole and hydroxyitraconazole in sputum
Time Frame: Part 3: baseline through 28 days
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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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Part 3: baseline through 28 days
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: James Roach, MD, Pulmatrix Inc.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Immune System Diseases
- Lung Diseases
- Hypersensitivity, Immediate
- Bronchial Diseases
- Lung Diseases, Obstructive
- Respiratory Hypersensitivity
- Hypersensitivity
- Asthma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Antifungal Agents
- Steroid Synthesis Inhibitors
- 14-alpha Demethylase Inhibitors
- Itraconazole
- Hydroxyitraconazole
Other Study ID Numbers
- 601-0013
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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