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)
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
58
Itraconazole administered as a dry powder for inhalation (PUR1900)
Sporanox® Oral Solution
Medicines Evaluation Unit
Manchester, United Kingdom
Quotient Sciences
Nottingham, United Kingdom
Number of participants with treatment-related Adverse Events as assessed by CTCAE v4.0
Safety and tolerability will be assessed by evaluating the 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
Area under the serum concentration vs time curve from time 0 to infinity (AUC0-inf) of single dose of itraconazole
The area under the serum concentration vs time curve from time 0 to infinity (AUC0-inf)
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Time of the maximum measured serum concentration (Tmax) of single dose of itraconazole
Time of the maximum measured serum concentration (Tmax)
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Area under the serum concentration vs time curve within the dosing interval (AUCtau) of single dose of itraconazole
The area under the serum concentration vs time curve within the dosing interval (AUCtau)
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 ) of single dose of itraconazole
Apparent first-order terminal elimination half-life (t1/2 )
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 the serum concentration vs time curve (Kel) of single dose of itraconazole
Apparent first-order terminal elimination rate constant calculated from a semi-log plot of
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Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Apparent clearance (CL/F) of single dose of itraconazole
Apparent clearance (CL/F)
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Apparent volume of distribution (Vz/F) of single dose of itraconazole
Apparent volume of distribution (Vz/F)
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28