Long‐term open‐label perampanel: Generalized tonic–clonic seizures in idiopathic generalized epilepsy

OBJECTIVE: Assess the longer‐term efficacy and safety of adjunctive perampanel (up to 12 mg/day) in patients aged ≥12 years with generalized tonic–clonic (GTC) seizures from the Open‐label Extension (OLEx) Phase of Study 332 to determine whether responses obtained during the Core Study are maintained during long‐term treatment. METHODS: Patients with GTC seizures previously enrolled in a randomized placebo‐controlled trial of perampanel could enter an OLEx Phase comprising 6‐week blinded conversion (during which patients previously randomized to placebo‐switched to perampanel) and up to 136‐week maintenance periods (maximum perampanel dose of 12 mg/day). A 4‐week follow‐up period was completed by all patients after the last on‐treatment visit during the OLEx. We assessed seizure frequency outcomes from preperampanel baseline and the Core Study Pre‐randomization Phase, retention rates, doses selected, and treatment‐emergent adverse events (TEAEs). RESULTS: Overall, 138 patients entered the OLEx. Median percent reductions in GTC seizures per 28 days from preperampanel were 77% (Weeks 1‐13) and 90% (Weeks 40‐52). Retention rates were 88% (6 months) and 75% (12 months). Seizure‐freedom rates were maintained for at least 2 years regardless of prior treatment received during the Core Study. Most common modal daily dose was >4‐8 mg/day (n = 93). Across the Core and OLEx Phases, 120 (87%) patients experienced TEAEs; the most common was dizziness. SIGNIFICANCE: Perampanel was generally well‐tolerated, and the TEAEs reported here are consistent with the known safety profile of perampanel. Perampanel offers a long‐term treatment option for patients (aged ≥12 years) with GTC seizures.