Abstracts

Rationale: Perampanel (PER), a selective, noncompetitive AMPA receptor antagonist, is approved in more than 35 countries for adjunctive treatment of partial-onset seizures (POS), with or without secondarily generalized seizures, in patients with epilepsy aged ≥12 yrs. Study 235 was designed primarily to compare the short-term effects of PER vs placebo (PBO) on cognition in adolescents (12 to <18 yrs of age) with inadequately controlled POS. Here we present an analysis of the efficacy and safety of PER as an antiepileptic drug (AED) in this patient population. Methods: Patients enrolled in this Phase II study were receiving 1-3 concomitant AEDs. Following up to 1-wk prospective baseline, patients were randomized to once-daily double-blind treatment (6-wk titration, 13-wk maintenance) with PBO or PER 2mg/day uptitrated weekly in 2mg increments to a target dose range of 8-12mg/day, with a 4-wk follow-up for patients not entering the open-label extension. Analysis of efficacy and safety was a secondary objective for Study 235, and thus the study is not powered to show significance between PER and PBO. Efficacy endpoints included median percent change in seizure frequency per 28 days during the double-blind phase vs baseline, and responder rate (patients who experienced a ≥50% reduction in seizure frequency) and seizure-free status during the maintenance period. Safety endpoints included treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results: The adolescent population in this study consisted of 133 patients (PER=85; PBO=48), with 53 (39.8%) female patients (PER=33; PBO=20) and mean age of 14.3 yrs (57.1% aged 12 to <15). Efficacy results are shown in Table 1. Patients receiving PER showed a median percent change in seizure frequency of -58.0%, compared to -24.0% in the PBO group. Responder rate was also greater in the PER group (49 patients, 59.0%) than the PBO group (17 patients, 37.0%). Seizure-free status was achieved by 18 (23.7%) and 7 (16.3%) patients in the PER and PBO groups, respectively. TEAEs occurred in 68 (80%) patients receiving PER and 31 (64.6%) patients receiving PBO (Table 2). TEAEs that were notably more frequent in the PER group compared with the PBO group were dizziness, somnolence, fatigue, aggression, irritability, and weight increased. Convulsions were seen more frequently with PBO. The majority of TEAEs in both treatment groups were considered mild or moderate. Treatment-emergent SAEs occurred in 5 (5.9%) PER and 2 (4.2%) PBO patients. TEAEs resulted in discontinuations in 3 (3.5%) patients in the PER group and 0 patients in the PBO group. Conclusions: Adjunctive therapy with PER at daily doses of up to 12mg resulted in improved seizure control and was safe and well tolerated in patients aged 12 to <18 yrs with inadequately controlled POS, consistent with adolescent data from previous Phase III studies. Support: Eisai Inc.