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Abstracts

Pulmonary Safety of Staccato® Alprazolam in Healthy Participants and Participants with Mild Asthma: Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial

Abstract number : 2.255
Submission category : 7. Anti-seizure Medications / 7B. Clinical Trials
Year : 2023
Submission ID : 397
Source : www.aesnet.org
Presentation date : 12/3/2023 12:00:00 AM
Published date :

Authors :
Presenting Author: Maria Burian, MD – UCB Pharma, Braine l'Alleud, Belgium

First Author: S. David Miller, MD – Northeast Medical Research Associates, North Dartmouth, MA

Craig LaForce, MD – North Carolina Clinical Research, Raleigh, NC, USA; Laura Barlow, PhD – Veramed, Twickenham, UK; Aliceson King, MD – UCB Pharma, Smyrna, GA, USA; Hugues Chanteux, PhD – UCB Pharma, l'Alleud, Belgium

Rationale:
Staccato® alprazolam is a hand-held device that can provide rapid systemic delivery of alprazolam via inhalation. UP0099 (NCT04802746) was conducted to evaluate the pulmonary safety of repeat dosing of Staccato® alprazolam in healthy participants and those with mild asthma.



Methods:
This randomized, double-blind trial evaluated 2 consecutive doses of Staccato® alprazolam administered 72 h apart (day 1 and 4) in adults aged 18-55 years. Part A evaluated Staccato® alprazolam 1mg and 2mg vs placebo in a 3-way crossover design in healthy participants. Part B evaluated Staccato® alprazolam 2mg vs placebo in a 2-arm parallel group design in participants with mild asthma diagnosed ≥6 months and on a stable asthma drug regimen for ≥4 weeks before screening. Primary endpoints: spirometric assessments of changes from baseline in forced expiratory volume in 1 second (FEV1); repeated measures ANCOVA; respiratory treatment-emergent adverse events (TEAEs).

Results:
Part A enrolled 30 participants (mean [SD] age 30.7 [9.7] years; 17 [56.7%] female); 2/30 participants discontinued. On day 1, mean FEV1 showed greater decrease vs placebo at 5 min postdose for Staccato® alprazolam 1mg (-0.076L vs -0.007L) and 2mg (-0.099L vs -0.007L) and at 20 min for Staccato® alprazolam 2mg (-0.080L vs -0.029L). These differences vs placebo were statistically significant but not considered clinically relevant. Mean FEV1 then returned to baseline and were similar to placebo (Figure A). On day 4, changes from baseline were less marked and similar across groups (Figure B). Respiratory TEAEs (cough) were reported by 8/29, 12/29, and 0/28 participants on Staccato® alprazolam 1mg, 2mg and placebo, respectively, on day 1, and by 8/29, 9/28 and 0/28 on day 4 (Table). Part B enrolled 48 participants (mean [SD] age 33.3 [8.5] years; 29 [60.4%] female). On day 1, mean FEV1 showed a greater decrease for Staccato® alprazolam 2mg vs placebo at 5 min (-0.245L vs -0.045L) and 20 min (-0.178L vs -0.013L) postdose (Figure C). These differences vs placebo were statistically significant but not considered clinically relevant. On day 4, mean decreases in FEV1 were less marked than on day 1 (Figure D). Respiratory TEAEs were reported by 16/23 participants on Staccato® alprazolam 2mg on day 1 (cough in 16/23, and bronchospasm, dyspnea [both not considered drug-related], dysphonia, throat irritation in 1/23 each), and by 15/22 participants on day 4 (cough: 15/22; throat irritation: 1/22) (Table). No respiratory TEAEs occurred with placebo.



Conclusions:
2 doses of Staccato® alprazolam (either 1mg or 2mg) administered 72 h apart were well tolerated in healthy participants and those with mild asthma. Minor decreases in FEV1 from baseline were observed with Staccato® alprazolam vs placebo at several timepoints; however these were not considered clinically relevant. No evidence of clinically relevant airway obstruction related to Staccato® alprazolam was observed in healthy participants and those with mild asthma. Most TEAEs were mild/moderate in intensity.

Funding: UCB Pharma-sponsored.

Anti-seizure Medications