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

Pulmatrix

Status and phase: Completed; Phase 1

Conditions: Asthma

Treatments: Drug: Itraconazole Powder; Drug: Itraconazole 200 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03479411

601-0013

Details and patient eligibility

About

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)

Full 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).

Enrollment: 58 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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58 participants in 3 patient groups

Part 1 single ascending dose

Experimental group

Description:

Intervention: drug Itraconzaole powder: single dose of 5mg, 10mg or 25 mg Other name: PUR1900

Treatment:

Drug: Itraconazole Powder

Part 2 multiple ascending dose

Experimental group

Description:

Intervention: drug Itraconzaole powder: 10 mg or 20 mg daily for 14 days Other name: PUR1900

Treatment:

Drug: Itraconazole Powder

Part 3 2-period crossover single dose

Active Comparator group

Description:

Intervention: drug Itraconzaole powder: 20 mg single dose and Itraconzaole oral solution 200 mg single dose Other names: PUR1900, Sporanox

Treatment:

Drug: Itraconazole 200 mg

Drug: Itraconazole Powder