A Single- and Multiple-Dose Pharmacokinetic Study of Oral Perampanel in Healthy Chinese Subjects

Abstract

Background and objective: Perampanel is a once-daily oral anti-seizure medication indicated for focal-onset seizures and generalized tonic-clonic seizures. This study investigated the single- and multiple-dose pharmacokinetics of perampanel in healthy Chinese adults.

Methods: Study 052 (NCT03424564) was a phase I, single-center, open-label, parallel-group study. In the single-dose part of the study, subjects received a single oral dose of perampanel 2, 4, or 8 mg. In the multiple-dose part, subjects received once-daily oral perampanel 2 mg on Days 1-7 and 4 mg on Days 8-21. Pharmacokinetic parameters were determined from perampanel plasma concentrations using non-compartmental analysis. Dose proportionality after single doses of perampanel was assessed. Safety and tolerability were evaluated.

Results: In the single-dose part (N = 30), median time to reach maximum concentration (t_max) was 0.75-1.0 h, mean terminal elimination phase half-life (t_½) was 85.6-122 h, mean maximum observed concentration (C_max) was 77.9-276 ng/mL, and mean area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC_(0-t)) was 4070-15100 ng·h/mL. Single-dose pharmacokinetics were linear for perampanel 2-8 mg. In the multiple-dose part (N = 12), Day 21 steady-state (4 mg/day) parameters were median time at which the highest drug concentration occurs at steady state (t_ss,max), 1.25 h; mean t_½, 109 h; mean maximum observed concentration at steady state (C_ss,max), 453 ng/mL; and mean area under the concentration-time curve over the dosing interval on multiple dosing (AUC_{(0- τ)}), 7540 ng·h/mL. For single- and multiple-dose perampanel, the most common treatment-emergent adverse events were dizziness and somnolence.

Conclusions: Single- and multiple-dose pharmacokinetics of perampanel in healthy Chinese adults revealed rapid perampanel absorption, slow elimination, and a linear relationship with single perampanel doses of 2-8 mg. Findings were consistent with previous studies of perampanel pharmacokinetics in other ethnic/racial populations of healthy subjects. Single and multiple doses of perampanel were generally safe and well tolerated.

Clinical trial registration: NCT03424564; registered February 2018.