Abstracts

Rationale: Perampanel (PER), an orally active, highly selective, noncompetitive AMPA antagonist, has been evaluated in 3 pivotal Phase 3 trials. Results from the separate trials have been presented previously; here, we present the pooled efficacy and safety results from 2 of the Phase 3 studies that included the North American (NA) patient subpopulation as compared to the overall pooled Phase 3 results. Methods: Patients ≥12 years of age with refractory partial seizures (treated with 1-3 AEDs) were randomized to once-daily, double-blind placebo (PBO), or PER 2, 4, 8, 12 mg/day. Studies 304 (N=388; conducted in North America, Central America, South America) and 305 (N=386; conducted in Europe, Asia, South Africa, North America, Australia) compared PBO with PER doses of 8 mg/day and 12 mg/day, and included patients from the United States (N=294) and Canada (N=25). Study 306 (N=706; PBO, 2 mg, 4 mg, 8 mg) was conducted in Australia, Europe, and Asia. Endpoints included median % change in seizure frequency/28 days and 50% responder rate and safety. Results: The NA patient cohort in the Phase 3 trials had long-standing disease (mean duration, 23.9 years), often with no known etiology (53.8%). Most had complex partial seizures (CP) (89.6%), and had a baseline history of seizures with secondary generalization (SG) (72.0%). The ITT population consisted of 318 patients (n=106, PBO; n=105, 8 mg; n=107, 12 mg). The safety population consisted of 319 patients (n=106, PBO; n=105, 8 mg; n=108, 12 mg). Median changes from baseline in seizure frequency/28 days during the double-blind period and the responder rates during maintenance-LOCF period for the NA subpopulation and the pooled Phase 3 population are presented in Table 1. For the NA patient pool, median % changes in seizure frequency/28 days in CP+SG during the double-blind period were -16.8 (N=97), -40.1 (N=102), and -34.9 (N=98) and in SG seizures were -10.7 (N=49), -60.6 (N=41), and -67.9 (N=41) for PBO, 8 mg, and 12 mg, respectively. In the overall Phase 3 population, these were -13.9 (N=405), -20.5 (N=167), -31.2 (N=157), -35.6 (N=393), and -28.6 (N=233) for CP+SG and -19.4 (N=173),-28.0 (N=68), -48.6 (N=71), -62.9 (N=157), -53.3 (N=95) for the SG seizures with PBO, 2 mg, 4 mg, 8 mg, and 12 mg, respectively. Study completion rates for the NA region were 86.8%, 90.5%, and 72.2% for PBO, 8 mg, and 12 mg, respectively. Treatment-emergent adverse events (TEAEs), occurring in ≥10% of patients, for the NA population and the overall Phase 3 population are presented in Table 2. Conclusions: PER was efficacious in the treatment of refractory partial onset seizures in the NA subpopulation, the majority of whom had CP, with and without SG, in the Phase 3 trials. Efficacy results both in terms of improvement in seizure frequency and responder rates in the NA subpopulation were consistent with the overall Phase 3 population. PER had a favorable safety profile and tolerability that was consistent with the overall study population.