Bioequivalence study of perampanel oral suspension in healthy Chinese subjects under fasting and fed conditions.

Abstract

Perampanel oral suspension (Fycompa^®) is indicated as adjunctive therapy for the treatment of partial-onset seizure and primary generalized tonic-clonic seizure. This study aimed to assess the bioequivalence of perampanel oral suspension and its generic under the fasting and fed conditions. A randomized, open-label, single-dose, 2-period crossover study was conducted in Chinese healthy subjects under fasting and fed conditions. Each period, subjects received either a 4-mg reference perampanel oral suspension or test product. Blood samples were collected at pre-dose and up to 96 h after administration. Plasma levels of perampanel were quantified using a validated LC-MS/MS method. A total of 74 volunteers were enrolled, 71 of whom completed the study. For the fasting study, the primary pharmacokinetic parameters (mean ± SD) were as follows: C_max was 138.1 ± 30.2 and 126.0 ± 22.7 ng/mL, AUC_0-t was 3998 ± 717 and 4194 ± 963 h*ng/mL, and AUC_0-72h was 3318 ± 567 and 3464 ± 763 h*ng/mL for the test and reference formulations, respectively. For the fed study, the corresponding values were as follows: C_max was 87.0 ± 17.2 and 81.5 ± 15.4 ng/mL, AUC_0-t was 4000 ± 991 and 3991 ± 896 h*ng/mL, and AUC_0-72h was 3190 ± 768 and 3156 ± 657 h*ng/mL for the test and reference products, respectively. The 90% confidence intervals for the geometric mean ratios of these parameters all met the bioequivalence criterion of 80-125%. There were 36 adverse events (AEs) reported in the fasting study, and 47 AEs in the fed study. The test and reference formulations of perampanel oral suspension were bioequivalent and well-tolerated under both fasting and fed conditions. This trial had been registered at the Chinese Clinical Trial Registry on April 20, 2023 ( https://www.chictr.org.cn/ , ChiCTR2300070693).