Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug for partial-onset seizures (POS) and primary generalized tonic-clonic seizures. The approval of adjunctive perampanel for the treatment of POS was based on efficacy and safety data from three randomized, double-blind, placebo-controlled, Phase III studies of adjunctive perampanel 2-12 mg/day in patients (aged >=12 years) with POS, with or without secondarily generalized (SG) seizures (Studies 304 [NCT00699972], 305 [NCT00699582], and 306 [NCT00700310]). Here, we report a pooled 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 Studies 304, 305, or 306. Methods: All studies comprised a 19-week Double-blind Period (6-week Titration; 13-week Maintenance). During Titration, perampanel patients received 2 mg/day before up-titration in weekly 2-mg increments to <=12 mg/day. For this analysis, the rate of TEAEs was analyzed by Treatment Period (Titration: Week[s] 1 [2 mg], 1-2 [4 mg], 1-4 [8 mg], 1-6 [12 mg]; Pre-steady-state: Weeks 2-4 [2 mg], 3-5 [4 mg], 5-7 [8 mg], 7-9 [12 mg]; Maintenance: Weeks 5-19 [2 mg], 6-19 [4 mg], 8-19 [8 mg], 10-19 [12 mg]) in patients who completed the study. Total exposure to perampanel for each 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 calculated as the number of events divided by total exposure, multiplied by 100. Results: Overall, 1480 patients with POS were treated during Studies 304, 305, and 306 (placebo, n=442; perampanel 2 mg, n=180; 4 mg, n=172; 8 mg, n=431; 12 mg, n=255). In total, 392/442 (88.7%) placebo-treated patients and 872/1038 (84.0%) perampanel-treated patients (2 mg, n=154 [85.6%]; 4 mg, n=158 [91.9%]; 8 mg, n=367 [85.2%]; 12 mg, n=193 [75.7%]) completed the 19-week Treatment Period. Total exposure to study drug (subject-months), overall rate of TEAEs, and the most common TEAEs during the Titration, Pre-steady-state, and Maintenance Periods are shown in Table 1 for the perampanel completer population. For all perampanel dose groups, the overall rate of TEAEs per 100 subject-months was highest in the Titration Period (46.6-59.7), lower during Pre-steady-state (28.6-52.3), and at the lowest level during the Maintenance Period (13.3-22.1). The most common TEAEs per 100 subject-months during the Titration Period across dose groups were dizziness (10.4-22.8) and somnolence (8.6-18.2); successively lower rates of these individual TEAEs were reported during the Pre-steady-state and Maintenance Periods (dizziness: 6.1-13.4 and 0.9-3.6; somnolence: 0.7-7.3 and 0.5-1.2, respectively; Table 1). Conclusions: These data suggest that adjunctive perampanel 2-12 mg/day is generally well tolerated in patients aged >