Pulmonary Safety of Staccato® Alprazolam in Healthy Participants and Participants with Mild Asthma: Phase 1, Randomized, Double-blind, Placebo-controlled Trial
S. David Miller1, Craig F. LaForce2, Laura Barlow3, Aliceson King4, Maria Burian4, Hugues Chanteux4
1Northeast Medical Research Associates, 2North Carolina Clinical Research, 3Veramed, 4UCB Pharma
Objective:
Evaluate pulmonary safety of repeat dosing of Staccato® alprazolam (STAP) in healthy participants and those with mild asthma.
Background:
STAP is a hand-held device providing rapid systemic delivery of alprazolam via inhalation.
Design/Methods:
UP0099 (NCT04802746) was a randomized, double-blind clinical study evaluating 2 doses of STAP administered 72h apart (Day1 and Day4) in adults (18-55yrs). Part-A evaluated STAP 1mg/2mg vs placebo in healthy participants. Part-B evaluated STAP 2mg vs placebo in participants with mild asthma. Primary endpoints: spirometric assessments of forced expiratory volume in 1sec (FEV1); repeated measures ANCOVA; respiratory treatment-emergent adverse events (respiratory-TEAEs).
Results:
Part-A enrolled 30 participants (mean age 30.7yrs; 56.7% female); 2/30 discontinued. Day1: mean FEV1 showed greater decrease from baseline vs placebo at 5min postdose for STAP 1mg (-0.076L vs -0.007L) and 2mg (-0.099L vs -0.007L) and at 20min for 2mg (-0.080L vs -0.029L). Differences were statistically significant but not clinically relevant. Day4: changes from baseline were less marked and similar across groups. Respiratory-TEAEs (all cough) were reported by 8/29, 12/29, and 0/28 participants on STAP 1mg, 2mg, and placebo, respectively, on Day1, and by 8/29, 9/28 and 0/28 on Day4. Part-B enrolled 48 participants (mean age 33.3yrs; 60.4% female); 1/48 discontinued. Day1: mean FEV1 showed greater decrease from baseline for STAP 2mg vs placebo at 5min (-0.245L vs -0.045L) and 20min (-0.178L vs -0.013L) postdose. Differences were statistically significant but not clinically relevant. Day4: changes from baseline in FEV1 were less marked than on Day1. Respiratory-TEAEs (most commonly cough) were reported by 16/23 participants on STAP 2mg on Day1, and 15/22 participants on Day4 (placebo: no respiratory-TEAEs).
Conclusions:
STAP (1mg/2mg) administered 72h apart was well tolerated in healthy participants and those with mild asthma. Minor decreases in FEV1 from baseline were observed with STAP vs placebo; these were not clinically relevant. Cough was the most common respiratory-TEAE.