Purpose

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

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 2
Study Type
Interventional
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.
Primary Purpose
Treatment
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.

Arm Groups

ArmDescriptionAssigned Intervention
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.

Recruiting Locations

University of Texas Medical Branch at Galveston
Galveston, Texas 77555
Contact:
Cindy Mitchell
409-772-5508
cimitche@utmb.edu

More Details

NCT ID
NCT03960606
Status
Recruiting
Sponsor
Pulmatrix Inc.

Study Contact

Russel G. Clayton, DO
781-357-2333
rclayton@Pulmatrix.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.