Assessment of the long-term efficacy and safety of adjunctive perampanel in tonic-clonic seizures: Analysis of four open-label extension studies.

Abstract

ObjectiveThis post hoc analysis evaluated long‐term efficacy and safety in patients with focal to bilateral tonic‐clonic seizures (FBTCS) or generalized tonic‐clonic seizures (GTCS) who entered open‐label extension (OLEx) studies to receive long‐term adjunctive perampanel.MethodsPatients aged 12 years and older who completed phase II or III randomized, double‐blind, placebo‐controlled studies could enter an OLEx study, each comprising a blinded conversion period followed by an open‐label maintenance period (32‐424 weeks; maximum perampanel dose = 12 mg/d). Exposure, seizure outcomes, and treatment‐emergent adverse events (TEAEs) were analyzed.ResultsBaseline characteristics were generally balanced between patients with FBTCS (n = 720) and GTCS (n = 138). Mean (standard deviation) cumulative duration of perampanel exposure was 102.3 (70.3) weeks (FBTCS) and 83.9 (38.4) weeks (GTCS). Retention rates were 50.0% for up to 4 years (FBTCS) and 49.2% for up to 2 years (GTCS). Across OLEx treatment durations, median reductions in seizure frequency per 28 days were 66.7% (FBTCS) and 80.6% (GTCS). Fifty percent and 75% responder and seizure‐freedom rates were 59.5%, 45.3%, and 18.4%, respectively (FBTCS), and 72.5%, 51.5%, and 16.7%, respectively (GTCS). Efficacy was sustained for up to 4 years (FBTCS) and up to 3 years (GTCS), even when accounting for early dropouts. TEAE incidence was highest during Year 1 (FBTCS, 85.3%; GTCS, 86.2%); most common were dizziness and somnolence. During Year 1, serious TEAEs were reported in 81 (11.3%; FBTCS) and 10 (7.2%; GTCS) patients. TEAEs were consistent with the known safety profile of perampanel; no new safety signals were identified with long‐term treatment.SignificanceThis post hoc analysis suggests long‐term (up to 4 years) adjunctive perampanel (up to 12 mg/d) is efficacious and well tolerated in patients (aged 12 years and older) with FBTCS or GTCS.