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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
7
National Jewish Health
Denver, Colorado, United States
Incidence of treatment-emergent adverse events
Time frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Incidence of intraday FEV1 declines
Time frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Respiratory rate
Time frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Blood pressure
Systolic pressure over diastolic pressure
Time frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Heart rate
Beats per minute
Time frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Oxygen saturation
As a percentage
Time frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Physical examination findings
Physician's notes
Time frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Clinical laboratory test results
Lab reports with any out of range results flagged
Time frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
12-Lead electrocardiogram findings
ECG report and tracing
Time frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
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Yale University School of Medicine
New Haven, Connecticut, United States
Integrity Clinical Research Center Inc.
Hialeah, Florida, United States
Heuer M.D Research Inc.
Miami Lakes, Florida, United States
Infinite Clinical Trials
Roswell, Georgia, United States
University Consultants In Allergy and Immunology
Chicago, Illinois, United States
Laporte County Institute for Clinical Research
Michigan City, Indiana, United States
Montefiore Medical Center
The Bronx, New York, United States
University of Texas Medical Branch at Galveston
Galveston, Texas, United States
John Hunter Hospital
New Lambton, New South Wales, Australia
...and 10 more locations
Sputum concentrations of itraconazole and hydroxy-itraconazole
Time frame: Day 2 to Day 28
Sputum eosinophils
Time frame: (Day -9 to Day -6) to Day 28
To evaluate the effect of PUR1900 on pulmonary function following single- and multiple-dose administration of PUR1900
Time frame: Day 1 to Day 28
Asthma Control Questionnaire-6 (ACQ 6)
Scores range between 0 (totally controlled) and 6 (severely uncontrolled).
Time frame: Day 1 to Day 28
Change from baseline (Day 1) to Day 28 in A fumigatus burden in sputum
As assessed by quantitative PCR and sputum culture
Time frame: Day 1 to Day 28
Cmax (maximum observed concentration in plasma)
Time frame: Day 1 to Day 28
Tmax (time to maximum concentration in plasma)
Time frame: Day 1 to Day 28
AUC (area under the concentration-time curve)
Time frame: Day 1 to Day 28
CL/F (clearance)
Time frame: Day 1 to Day 28
Vz/F (apparent volume of distribution)
Time frame: Day 1 to Day 28