Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug for partial-onset seizures and primary generalized tonic-clonic (PGTC) seizures. Study 332 (NCT01393743) was a multicenter, randomized, double-blind, placebo-controlled, Phase III study of adjunctive perampanel (up to 8 mg/day) in patients aged >=12 years with idiopathic generalized epilepsy (IGE) and PGTC seizures. Here, we report a post hoc safety analysis examining the rate of TEAEs during the Titration, Pre-steady-state, and Maintenance Periods in patients who received perampanel and completed Study 332. Methods: Study 332 consisted of a 17-week Double-blind Treatment Period (4-week Titration; 13-week Maintenance). During Titration, patients in the perampanel group received an initial dose of 2 mg/day, before up-titration in weekly 2-mg increments to a target dose of 8 mg/day. For this post hoc analysis, the rate of TEAEs was analyzed by Treatment Period (Titration: Weeks 1-4; Pre-steady-state: Weeks 5-7; Maintenance: Weeks 8-17) in patients who received perampanel and completed the study. Total exposure to perampanel for each Treatment Period, in subject-months (1 month=28 days), was calculated as the sum of durations of exposure for all patients across that period. TEAE rates were then calculated as the number of events divided by the total exposure, multiplied by 100.  Results: Overall, 163 patients with PGTC seizures were treated during Study 332 (placebo, n=82; perampanel, n=81). Of these, 140 (85.9%) patients completed the 17-week Treatment Period, with similar proportions of patients completing the study in the placebo (n=72 [87.8%]) and perampanel (n=68 [84.0%]) groups. In the perampanel completer population, total exposure to study drug was 68.0, 51.0, and 168.9 subject-months during the Titration, Pre-steady-state, and Maintenance Periods, respectively. A summary of overall TEAEs and the most common TEAEs in each of the Treatment Periods is given in Table 1. The overall rate of TEAEs per 100 subject-months was highest in the Titration Period (61.8), then lowered during Pre-steady-state (45.1), and was lowest during the Maintenance Period (22.5). The most common TEAEs per 100 subject-months during the Titration Period were dizziness, fatigue, headache, and somnolence; successively lower rates of these individual TEAEs were reported during the Pre-steady-state and Maintenance Periods (Table 1). Conclusions: These data suggest that adjunctive perampanel is generally well tolerated in patients (aged >=12 years) with IGE and PGTC seizures. In general, the highest TEAE rate was reported during the Titration Period and decreased over time, suggesting tolerability to perampanel treatment may improve as a patient reaches the Maintenance Period.  Funding: Eisai Inc.