Bioequivalence of Alprazolam Sublingual Tablet Formulation and Alprazolam Immediate Release Tablet in Healthy Volunteers

Abstract

Alprazolam immediate release (IR) tablets are currently approved for the management of anxiety disorder or the short-term relief of symptoms of anxiety. A sublingual (SL) formulation of alprazolam, which disintegrates in the mouth without the need for additional fluids, has been developed. The aim of this study was to determine if the alprazolam SL 1 mg tablet was bioequivalent to the alprazolam IR 1 mg tablet in healthy volunteers. In this randomized, open label, two-way crossover, single dose study, subjects were randomized to receive a single alprazolam 1 mg IR tablet during one dosing period and a single 1 mg SL tablet during the other dosing period. The primary pharmacokinetic endpoints were area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration AUC (0-t) and maximum plasma concentration (C max ). Adverse events (AEs) were monitored throughout the study. Bioequivalence was concluded if the 90% confidence intervals (CI) for the ratio of adjusted geometric means for both AUC (0-t) and C max were wholly within 80%-125%. Participants were mostly male (27/28 [96.4%]) and had a mean (standard deviation) age of 35.9 (8.2) years. For the alprazolam 1 mg SL tablet relative to the alprazolam 1 mg IR tablet, the ratio of adjusted geometric means (90% CI) for AUC (0-t) and C max were 95.43% (91.74%, 99.27%) and 88.27% (83.68%, 93.11%), respectively. The incidence of AEs was similar during both treatment periods: 24 participants reported 39 AEs during the alprazolam 1 mg IR treatment period, and 23 participants reported 38 AEs during the alprazolam 1 mg SL treatment period. Bioequivalence was demonstrated between the alprazolam IR and SL 1 mg tablets, suggesting that the clinical performance of the SL tablet will be similar to that of the IR tablet.