Efficacy of Adjunctive Perampanel in Phase III Clinical Trials: Subanalysis of Change in Seizure Frequency and Responder Rates by Concomitant Antiepileptic Drug Use (S56.006)

Abstract

Objective: Assess effect of concomitant antiepileptic drugs (AEDs) on seizure frequency and responder rate in a pooled analysis of perampanel phase III studies. Background In phase III trials, adjunctive perampanel was efficacious in reducing uncontrolled partial-onset seizures (4-12 mg/day). Design/Methods: Following Baseline, patients (≥12 years, receiving 1-3 AEDs) were randomized to once-daily double-blind treatment with placebo or perampanel 2, 4, 8, or 12 mg. Efficacy endpoints were analyzed with respect to concomitant use of the most frequently taken AEDs (in any combination) to test if addition of these AEDs with other mechanisms of action affected the efficacy of perampanel. Endpoints analyzed were: percent change in seizure frequency/28 days (Double-blind Phase vs Baseline) and 50% responder rate (Maintenance vs Baseline). Results: Across the phase III studies, 1478 patients were randomized and treated (placebo, n=441; perampanel 2 mg, n=180; 4 mg, n=172; 8 mg, n=431; 12 mg, n=254), and were taking an average of 2.2 concomitant AEDs. The most common AEDs (≥45 patients/treatment group), used in combinations of 1-3 concomitant AEDs, were: carbamazepine (n=491), valproate (n=478), lamotrigine (n=457), and levetiracetam (n=435). Median differences (Hodges-Lehmann) in median percent change in seizure frequency/28 days in patients receiving concomitant AED combinations including carbamazepine, valproate, lamotrigine, or levetiracetam compared with placebo ranged from: 7.7% to -7.8% with perampanel 2 mg; -3.0% to -12.7% with 4 mg; -8.9% to -20.8% with 8 mg; and -12.4% to -16.7% with 12 mg. Responder rate ranges for these patients were: 13.6-23.1% with placebo; 13.8-21.4% with perampanel 2 mg; 19.6-34.7% with 4 mg; 29.7-38.3% with 8 mg; and 30.6-43.0% with 12 mg. Conclusions: Perampanel (4-12 mg/day) decreased seizure frequency and increased responder rates in patients concomitantly taking at least one of the four most common AEDs. The presence of another AED mechanism did not appear to reduce the efficacy of perampanel. Supported by: Eisai Inc. Disclosure: Dr. French has nothing to disclose. Dr. Ben-Menachem has received personal compensation for activities with Eisai Inc, UCB Pharma, Cyberonics, Inc., GlaxoSmithKline, Inc. and Lundbeck Research USA as an advisory board participant and/or speaker. Dr. Ben-Menachem has received personal compensation in an editorial capacity for Acta Neurologica Scandinovica. Dr. Ben-Menachem has received research support from Eisai Inc, UCB Pharma and Bial. Dr. Brodie has received personal compensation for activities with Pfizer Inc, UCB Pharma, Eisai Inc., GlaxoSmithKline, Inc., Sanofi-Aventis Pharmaceuticals, Inc., and Lundbeck Research USA, Inc. Dr. Brodie has received research support from Eisai Inc. Dr. Squillacote has received personal compensation for activities with Eisai as an employee. Dr. Yang has received personal compensation for activities with Eisai, Inc. as an employee. Dr. Kumar has received personal compensation for activities with Eisai Inc. as an employee. Dr. Laurenza has received personal compensation for activities with Eisai as an employee.