Abstracts

Rationale: Perampanel is a selective, non-competitive AMPA receptor antagonist. It is approved in >50 countries as adjunctive treatment for partial-onset seizures with or without secondary generalization in patients with epilepsy aged ?-12 years. Our studies investigated the safety and efficacy of perampanel in Japanese patients. Methods: Patients (?-12 years of age) with partial-onset seizures with or without secondarily generalized seizures receiving 1?"3 concomitant antiepileptic drugs were enrolled in study 231. In the Titration Period, perampanel was started at 2 mg/day and up-titrated in increments of 2 mg at weekly intervals up to 12 mg/day, unless up-titration was deemed inappropriate due to tolerability. The Week 6 dose was maintained in the Maintenance Period. Safety and tolerability of perampanel up to 12 mg/day were evaluated. The Tolerability and Safety Evaluation Committee (TSEC) investigated the maximum tolerable dose based on the protocol definition. Patients who completed study 231 were invited to participate in study 233 to evaluate the long-term safety and efficacy of perampanel. Results: In study 231, 23 of 30 patients who received perampanel completed the study. The rates of completers for each dose were 0% (0/23) at 2 mg, 4.3% (1/23) at 4 mg, 13.0% (3/23) at 6 mg, 17.4% (4/23) at 8 mg, 21.7% (5/23) at 10 mg, and 43.5% (10/23) at 12 mg. All adverse events (AEs) were moderate or mild in terms of severity, and AEs leading to study drug discontinuation, dose reduction, or dose interruption were central-nervous-system-related events which, in the safety analysis set, were dizziness (53.3% [16/30]) and somnolence (46.7% [14/30]). Based on TSEC review, the proportion of patients at the tolerable dose was 33.3% (10/30) at 12 mg, 50.0% (15/30) at 10 mg or higher, and 70.0% (21/30) at 8 mg or higher. The median percent change in seizure frequency during the Maintenance Period was -35.0% for last observation carried forward (n=27). Seizure freedom was achieved in four patients. Of the 23 patients who completed study 231, 21 patients were enrolled in study 233. Of these, 90.5% (19/21) received perampanel for >24 weeks, 81.0% (17/21) for >72 weeks (>1 year), and 42.9% (9/21) for >216 weeks (>4 years). The median percent change in seizure frequency was -49.4% for Weeks 41?"52 (n=17), -52.5% for Weeks 101?"112 (n=16), -41.1% for Weeks 149?"160 (n=12), and -83.5% for Weeks 197?"208 (n=9). The most frequently (?-20%) reported AEs were nasopharyngitis (66.7%, n=14), contusion (52.4%, n=11), dizziness and somnolence (28.6%, n=6 each). Conclusions: In study 231, more than 80% of study completers received perampanel 8 mg/day or higher. Overall seizure reduction rate was comparable to other studies. In study 233, perampanel up to 12 mg/day maintained therapeutic effects and demonstrated a favorable safety profile in Japanese patients with refractory partial-onset seizures when given for as long as 4 years. Funding: Eisai Co., Ltd.