Efficacy and safety of perampanel in generalized and focal to bilateral tonic-clonic seizures: A comparative study of Asian and non-Asian populations.

Abstract

Perampanel is an approved adjunctive treatment for focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures and generalized tonic-clonic (GTC) seizures. We compared efficacy and safety of perampanel vs placebo in Asian and non-Asian populations in a post hoc analysis of pooled data from 5 randomized phase 3 studies. Patients (≥12years old) with focal+FBTC seizures received perampanel 2, 4, 8, or 12mg or placebo; patients with GTC seizures received perampanel 8mg or placebo (titration: 4-6weeks; maintenance: 13weeks). Efficacy endpoints included median percentage change in FBTC or GTC seizure frequency per 28days and 50% responder rate relative to baseline. Median percentage change in FBTC seizure frequency was significantly greater for perampanel 8 and 12mg than placebo in the Asian population (median difference from placebo: -30.32%, P=0.0017; -30.06%, P=0.0008, respectively) and perampanel 4, 8, and 12mg in the non-Asian population (-35.07%, P=0.0001; -37.78%, P<0.0001; -34.53%, P<0.0001, respectively). In both populations, median percentage change in GTC seizure frequency was significantly greater for perampanel 8mg than placebo (median difference from placebo: Asian, -37.37%, P=0.0139; non-Asian, -27.04%, P=0.0006). The 50% responder rates were significantly greater than placebo for perampanel 8 and 12mg for FBTC seizures (Asian: 58.0%, P=0.0017 and 58.6%, P=0.0013, respectively; non-Asian: 59.3%, P<0.0001 and 54.3%, P=0.0050, respectively) and perampanel 8 mg for GTC seizures (Asian: 57.6%, P=0.0209; non-Asian: 68.8%, P=0.0329). Pooled FBTC/GTC seizure data showed generally similar patterns of response to perampanel in both populations. The most frequent treatment-related adverse events were fatigue, irritability, dizziness, somnolence, and headache. Perampanel was effective, well tolerated, and can be considered a therapeutic option for FBTC/GTC seizures in Asian populations.