Pharmacokinetics of Staccato® Alprazolam in Healthy Adult Participants: Phase 1, Randomized, Placebo-controlled Ethno-bridging Study
Robert Roebling1, Yoshinobu Hayakawa1, Chiara C Rospo1, Ana Paula Bartmann1, Aliceson King1, Hugues Chanteux1
1UCB Pharma
Objective:

Evaluate safety, tolerability, and pharmacokinetics of Staccato® alprazolam compared with placebo in healthy Japanese, Chinese, and Caucasian participants.

Background:

Staccato® alprazolam is a hand-held device that can provide rapid systemic delivery of alprazolam via inhalation.

Design/Methods:
Phase 1, double-blind, placebo-controlled study (UP0101/NCT04782388) in healthy Japanese, Chinese, and Caucasian participants aged 18–55 years randomized 4:1 to a single inhaled dose of Staccato® alprazolam 2 mg or Staccato® placebo. Primary (Japanese and Chinese participants) and secondary (Caucasian participants) pharmacokinetic endpoints were Cmax, AUCinf and AUC0-t. Primary safety endpoints were treatment-emergent adverse events (TEAEs) and serious TEAEs in Japanese and Chinese participants.
Results:

10 participants each of Japanese, Chinese, and Caucasian ethnicities were randomized; all completed the study. Following Staccato® administration, alprazolam was rapidly absorbed and distributed with a median Tmax of 1.5–2 min followed by typical biphasic elimination. The distribution phase was very short (5–10 min), leading to a sharp peak, then plasma concentrations steadily declined until 48 hours post-dose. GeoMean Cmax of alprazolam was numerically higher for Japanese (93.0 ng/mL) and Chinese (56.6 ng/mL) versus Caucasian (37.4 ng/mL) participants (Japanese/Caucasian ratio estimate [90% CI]: 2.488 [1.515, 4.087]; Chinese/Caucasian ratio estimate [90% CI]: 1.515 [0.922, 2.489]). GeoMean alprazolam AUCinf values were similar for Japanese (529.0 h*ng/mL) and Chinese (460.8 h*ng/mL) versus Caucasian (526.7 h*ng/mL) participants (Japanese/Caucasian ratio estimate [90% CI]: 1.004 [0.776, 1.299]; Chinese/Caucasian ratio estimate [90% CI]: 0.875 [0.676, 1.132]); AUC0-t showed a similar trend to AUCinf. The incidence of TEAEs with Staccato® alprazolam was similar between Japanese (8/8 [100%]), Chinese (6/8 [75%]), and Caucasian participants (8/8 [100%]). No serious TEAEs were reported.

Conclusions:

Alprazolam was rapidly absorbed (median Tmax of 1.5–2 min) when administered with the Staccato® device. No ethnic differences were observed based on AUCinf and AUC0-t suggesting no need for dose adjustments. Staccato® alprazolam was generally well tolerated.

10.1212/WNL.0000000000204981