Abstracts

Rationale: Perampanel is a selective, noncompetitive antagonist of the AMPA receptor. It is approved in over 40 countries as adjunctive treatment for partial-onset seizures with or without secondary generalization in patients with epilepsy aged ≥12 years (Canada ≥18 years). This study investigated the efficacy and safety of perampanel in patients from the Asia-Pacific region.Methods: Patients (male and female, ≥12 years of age) with partial-onset seizures with or without secondarily generalized seizures receiving 1-3 concomitant antiepileptic drugs were randomized 1:1:1:1 to perampanel 4, 8, or 12 mg/day, or placebo. The study comprised a 6-week Pre-randomization Phase (Baseline Phase) and a 19-week Randomization Phase (Treatment Phase: 6-week Titration and 13-week Maintenance). The primary efficacy endpoint was percent change in seizure frequency per 28 days for the Randomization vs Pre-randomization Phases. Secondary efficacy endpoints included responder rate (patients with ≥50% seizure reduction) and change in seizure frequency per 28 days by seizure type.Results: Of 710 patients randomized, 707 received ≥1 dose of study drug (perampanel 4 mg, n=176; 8 mg, n=175; 12 mg, n=180; placebo, n=176). Median percent changes in seizure frequency were -17.3%, -29.0%, -38.0% and -10.8% for perampanel 4, 8, and 12 mg, and placebo, respectively, and statistically significant for perampanel 8 (P=0.0003) and 12 mg (P<0.0001). 50% responder rates were greater for perampanel 4, 8, and 12 mg (23.0%, 36.0%, and 43.3%, respectively) vs placebo (19.4%), and statistically significant for perampanel 8 (P=0.0005) and 12 mg (P<0.0001). Median percent changes in complex partial seizure plus secondarily generalized seizure frequency were greater with perampanel 4, 8, and 12 mg (-19.1%, -33.7%, and -41.8%, respectively) vs placebo (-11.7%). Median percent changes in secondarily generalized seizure frequency were also greater with perampanel 4, 8, and 12 mg (-17.9%, -45.1%, and -52.5%, respectively) vs placebo (-12.1%). Seizure-free status was achieved during the Maintenance Period in 2.9%, 4.0%, 4.4%, and 0.6% of patients receiving perampanel 4, 8, and 12 mg, and placebo, respectively. Incidence of treatment-emergent adverse events (TEAEs) was 68.8%, 73.7%, 86.7%, and 66.5% with perampanel 4, 8, and 12 mg, and placebo, respectively. Most frequently reported (≥10%) TEAEs for perampanel 4, 8, 12 mg, and placebo, respectively were dizziness (22.7%, 28.6%, 42.2%, 5.7%), somnolence (15.9%, 17.7%, 17.8%, 13.1%), and nasopharyngitis (13.1%, 13.7%, 12.8%, 14.8%).Conclusions: Perampanel (4, 8, and 12 mg/day) reduced seizure frequency with a clear dose-response relationship, and was safe and well tolerated. As adjunctive therapy, perampanel demonstrated a favorable risk/benefit balance in adolescent and adult patients from the Asia-Pacific region who had refractory partial-onset seizures. Funding: This study was funded by Eisai Co., Ltd.