Pulmonary safety of Staccato alprazolam in healthy participants and participants with mild asthma: Phase 1, randomized, double-blind, placebo-controlled trial.

Staccato alprazolam (STAP) is a hand-held device that can provide rapid systemic delivery of alprazolam via pulmonary inhalation. UP0099/NCT04802746, a phase 1, randomized, double-blind, placebo-controlled trial, evaluated pulmonary safety of two consecutive doses of STAP administered 72 h apart (days 1, 4). Part A evaluated STAP 1 mg and 2 mg vs. placebo in a three-way crossover design in healthy adults. Part B evaluated STAP 2 mg vs. placebo in a two-arm parallel-group design in adults with mild asthma. In Part A (n = 30 randomized) on day 1, mean change from baseline in forced expiratory volume in 1 s (FEV1) showed a statistically significant decrease vs. placebo at 5 min postdose for STAP 1 mg and 5/20 min for STAP 2 mg. On day 4, there were no statistically significant negative changes from baseline in FEV1. Respiratory treatment-emergent adverse events (TEAEs) were reported by 8/29 and 12/29 participants on STAP 1 mg/2 mg, respectively (day 1), and 8/29 and 9/28 (day 4) (placebo: 0). In Part B (n = 25 placebo, n = 23 STAP) on days 1 and 4, mean change from baseline in FEV1 showed a statistically significant decrease for STAP 2 mg vs. placebo at 5/20 min and 6 h postdose. Respiratory TEAEs were reported by 16/23 participants on STAP 2 mg on day 1, 15/22 on day 4 (placebo: 0). Most respiratory TEAEs were mild in intensity. No evidence of clinically relevant airway obstruction or respiratory TEAEs indicative of bronchospasm with STAP were observed. Two doses of STAP (1 mg/2 mg) administered 72 h apart were well tolerated in healthy participants and those with mild asthma.