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

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

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 T_max 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 C_max 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 AUC_inf 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]); AUC_0-t showed a similar trend to AUC_inf. 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.

Alprazolam was rapidly absorbed (median T_max of 1.5–2 min) when administered with the Staccato^® device. No ethnic differences were observed based on AUC_inf and AUC_0-t suggesting no need for dose adjustments. Staccato^® alprazolam was generally well tolerated.