Efficacy, safety, and tolerability of perampanel in Asian and non-Asian patients with epilepsy.

Abstract

People of different ethnic or racial backgrounds may experience variations in pharmacokinetic and pharmacodynamic responses to drug therapies. Our post hoc analysis evaluated the efficacy, safety, and tolerability of perampanel in Asian and non-Asian populations with refractory focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures. This analysis pooled data from 4 randomized, placebo-controlled, phase-3 studies involving patients aged ≥12years who have focal seizures with or without FBTC seizures. Patients were receiving 2, 4, 8, or 12mg perampanel (or placebo) by the end of a 6-week titration period and for a further 13weeks during the maintenance phase. Efficacy endpoints included median percent change in seizure frequency per 28days, and 50% and seizure-freedom responder rates relative to baseline. The median percent change in seizure frequency per 28days from baseline was significantly greater than placebo for perampanel 8 and 12mg (-31.1% and -38.1% change, respectively; each P<0.0001) in the Asian population, and for perampanel 4, 8, and 12mg (-21.1% [P=0.0001], -26.3% [P<0.0001], and -27.7% [P=0.0001] change, respectively) in the non-Asian population. The 50% responder rate relative to baseline was significantly greater than placebo for perampanel 8 and 12mg (40.1% and 43.8%, respectively; each P<0.0001) in the Asian population, and for perampanel 4, 8, and 12mg (29.4% [P=0.0002], 32.8% [P<0.0001] and 34.5% [P=0.0001]), respectively, in the non-Asian population. Seizure-freedom rate among all patients was 4.9%-11.7% for perampanel 2, 4, 8, and 12mg. The most frequently reported treatment-emergent adverse events (TEAEs) across both populations were dizziness, somnolence, irritability, headache, and fatigue. The most common psychiatric TEAEs were aggression and irritability. Perampanel demonstrated a favorable and similar risk-benefit profile in both Asian and non-Asian populations with refractory focal seizures.