Bioavailability, safety and tolerability of intravenous brivaracetam in healthy Japanese participants

Abstract

1. We characterised the bioavailability, safety, and tolerability of brivaracetam 100 mg intravenous bolus and 15-min infusion versus oral reference tablet in 24 healthy Japanese participants.

2. In this randomised, open-label, three-period crossover study, participants received three 100 mg single doses of brivaracetam, intravenous bolus, infusion, and oral tablets. Maximum plasma concentration (C_max), area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (AUC_t), and area under the plasma concentration-time curve extrapolated to infinity (AUC_inf), were compared using analysis of variance following logarithmic transformation. Bioavailability comparisons were based on the 90% confidence intervals (CIs) around the geometric least squares means ratios (intravenous:oral). Safety and tolerability were monitored throughout the study.

3. The 90% CIs around AUC_t and AUC_inf ratios were entirely contained within the bioequivalence limits (0.80–1.25), but C_max was outside the limits (90% CI: 1.77–2.08 and 1.44–1.70 for intravenous bolus and infusion, respectively). All participants completed the study. Brivaracetam was well tolerated.

4. Because response to brivaracetam in epilepsy is related to exposure (AUC), no dose adjustment is warranted when switching from oral to intravenous dosing. However, investigations are needed to assess the safety and tolerability of intravenous administration in Japanese patients with epilepsy.

Keywords:

• Epilepsy
• anticonvulsants
• SV2A
• pharmacokinetics
• clinical pharmacology

Acknowledgements

The authors thank Yoichiro Ogama (Souseikai Sumida Hospital, Tokyo, Japan), for conducting the clinical trial as principal investigator, Yoshihiro Muramoto (UCB Pharma, Tokyo, Japan) for statistical support, and Jeffrey Long (UCB Pharma, Brussels, Belgium) and Giulia Leonetti (PRA Health Sciences, Assen, The Netherlands) for bioanalytical support. The authors acknowledge Kyoko Hirano, CMPP (UCB Pharma, Tokyo, Japan) for publication coordination and Aramedic Co., Ltd. for writing support, which was funded by UCB Pharma.

Disclosure statement

This study was supported by UCB Pharma, which was responsible for the design and conduct of the study, and collection, management, and analysis of the data. All authors were employed by UCB Pharma when the study was performed. The authors had final responsibility for the content.