21 Adjunctive Perampanel for Focal-Onset Seizures and Generalized Tonic-Clonic Seizures: Time to Seizure Onset in Phase III Studies

Abstract

In the US, perampanel is approved for focal-onset seizures (FOS; adjunctive and monotherapy) in patients aged ≥4 years, and adjunctive treatment of generalized tonic-clonic seizures (GTCS) in patients aged ≥12 years. Adjunctive perampanel 4–12 mg/day has previously shown efficacy and safety in randomized, double-blind, placebo-controlled Phase III studies in patients aged ≥12 years with FOS (Studies 304 [NCT00699972], 305 [NCT00699582], and 306 [NCT00700310]) or GTCS (Study 332 [NCT01393743]). This post hoc analysis further evaluates the efficacy of adjunctive perampanel for FOS (at a low dose of 4 mg/day) and GTCS (at 8 mg/day) by assessing time to first seizure following perampanel administration. In studies 304, 305, and 306, patients with FOS were randomized to placebo or adjunctive perampanel 2–12 mg/day (19-week double-blind treatment period [6-week titration; 13-week maintenance]). In Study 332, patients with GTCS were randomized to placebo or adjunctive perampanel 8 mg/day (17-week double-blind treatment period [4-week titration; 13-week maintenance]). Time to first seizure onset from day 1 of placebo or perampanel (4 mg/day, FOS; 8 mg/day, GTCS) administration was assessed in the intent-to-treat (ITT; FOS) or full (GTCS) analysis sets using the Kaplan–Meier method. For FOS, placebo data were available from all three studies; perampanel 4-mg/day data were from Study 306 (the only study to include the randomized 4-mg/day dose). For FOS, the ITT analysis set included 437 placebo-treated patients (182 from Study 306) and 168 patients who received perampanel 4 mg/day. Perampanel 4 mg/day was associated with longer time to first seizure vs placebo: mean (median [range]) time to first seizure was 9.3 (3 [1, 135]) days with perampanel 4 mg/day vs 4.9 (3 [1, 73]) and 4.5 (3 [1, 73]) days for study 306 placebo and pooled placebo, respectively. For GTCS, the full analysis set included 162 patients (placebo, n=81; perampanel, n=81). Compared with placebo, adjunctive perampanel 8 mg/day was associated with a longer time to first GTCS: mean (median [range]) time to first GTCS was 27.0 (12 [1, 126]) days for placebo and 45.3 (19 [1, 127]) days for perampanel 8 mg/day, respectively. Adjunctive treatment with once-daily perampanel 4 mg/day or 8 mg/day delayed the time to first seizure in patients aged ≥12 years with FOS or GTCS, respectively, compared with placebo. These data are consistent with the primary efficacy endpoints from studies 304, 305, 306, and 332, and further support the efficacy of perampanel for FOS and GTCS.