056 Perampanel and secondarily generalised seizures in a pooled analysis of phase III studies and their open-label extension: effect of enzyme-inducing antiepileptic drugs

Abstract

Purpose: Perampanel is approved for adjunctive treatment of partial seizures, with or without secondarily generalised seizures (SGS), and primary generalised tonic‐clonic seizures in epilepsy patients aged ≥12 years. Approval of perampanel for partial seizures was based on three randomised, double‐blind, placebo‐controlled, Phase III Studies 304 (NCT00699972), 305 (NCT00699582) and 306 (NCT00700310); patients completing these could enter open‐label extension (OLEx) Study 307 (NCT00735397). Here, we report efficacy of perampanel as adjunctive treatment of SGS by co‐administration of enzyme‐inducing antiepileptic drugs (EIAEDs) versus non‐EIAEDs in both the Phase III and OLEx studies. Method: In the double‐blind studies, patients (≥12 years) with partial seizures, with or without SGS, receiving 1‐3 AEDs at Baseline were randomised to placebo or 2‐12 mg/ day perampanel for 19 weeks. In the OLEx, patients received ≤12 mg/day perampanel for ≤272 weeks. Efficacy assessments included median percent change in SGS frequency/ 28 days, SGS 50% and 75% responder and seizurefreedom rates. Results: For patients with SGS at pre‐perampanel Baseline, 564 were in the double‐blind studies, and 388 received perampanel for ≥1 year in the OLEx. In the double‐ blind studies, perampanel co‐administered with an EIAED (carbamazepine, eslicarbazepine, oxcarbazepine, phenytoin) had reduced efficacy compared with non‐ EIAEDs due to increased clearance; this was particularly evident at higher doses, although these differences were still greater than placebo. In the OLEx, concomitant administration of both non‐EIAEDs and EIAEDs was associated with sustained efficacy, with slightly better efficacy during the first, second and third years of perampanel exposure for non‐EIAEDs compared with EIAEDs. Conclusion: Perampanel demonstrated good and sustained long‐term efficacy against SGS. With the recent FDA approval of perampanel for monotherapy use for partial seizures, non‐EIAED data may be more relevant for consideration if perampanel is used as a single agent (no other AED) while real‐world data and experience are accumulated.