Bioequivalence and Safety Assessment of Brivaracetam Dry Syrup Compared With Tablets in Healthy Japanese Participants: Results From Two Randomized Single- and Multiple-Dose Trials.

Abstract

The antiseizure medication brivaracetam is available as tablets, oral solution, and solution for intravenous injection in many countries. A dry syrup formulation is being developed for use in Japan. We report two phase 1, single-center, open-label, randomized, two-way crossover trials that assessed bioequivalence, safety, and tolerability of brivaracetam dry syrup and tablet formulations in healthy adult male Japanese participants. EP0110 (NCT05315947) assessed brivaracetam 50 mg dry syrup versus tablet after a single administration (N = 24). Although pharmacokinetic profiles were similar and bioequivalence criteria for AUC were met, bioequivalence criteria for the observed C_max were not met in this trial. A subsequent simulation of parameters at steady state, based on EP0110 data, indicated that bioequivalence could be established in a multiple-dose setting. EP0231 (NCT06312566) was designed employing a group sequential design (N = 96) and assessed brivaracetam 50 mg dry syrup versus tablet after multiple oral doses (N = 64). The point estimates (92.016% CIs) for C_max and AUC at steady state fell within the acceptable range for bioequivalence (0.80-1.25). Bioequivalence of dry syrup and tablet formulations was demonstrated after multiple doses. Single and multiple doses of brivaracetam 50 mg administered as dry syrup or tablet formulation were generally safe and well tolerated in healthy Japanese participants.