Abstracts

Rationale: Perampanel, a selective, non-competitive AMPA receptor antagonist, is approved for adjunctive treatment of partial seizures, with or without secondarily generalized (SG) seizures, and for primary generalized tonic-clonic (PGTC) seizures in patients with epilepsy aged ≥12 years. In Phase II/III randomized, double-blind, placebo-controlled studies, adjunctive perampanel (≤12 mg/day) demonstrated efficacy and tolerability in adult and adolescent patients with partial seizures, with or without SG seizures (Studies 206 [NCT00144690], 208 [NCT00416195], 304 [NCT00699972], 305 [NCT00699582], 306 [NCT00700310], 335 [NCT01618695], and 235 [NCT01161524]), or PGTC seizures and idiopathic generalized epilepsy (Study 332 [NCT01393743]). Patients who completed these studies were eligible to enter OLEx studies (Studies 207 [NCT00368472; Studies 206 and 208], 307 [NCT00735397; Studies 304, 305, and 306], 335 OLEx, 235 OLEx, and 332 OLEx [NCT02307578]). Here, we report post hoc analyses of long-term efficacy and safety outcomes in adolescent patients (aged ≥12 to ≤17 years) with generalized tonic-clonic (GTC) seizures (SG or PGTC) from the OLEx studies. Methods: All OLEx studies comprised a blinded Conversion Period (6–16 weeks across studies), where perampanel dose optimization was achieved (≤12 mg/day), followed by a Maintenance Phase (27–424 weeks; ≤1 to ≤8 years’ exposure, across studies). Patients who received placebo during the Double-blind Phase were converted to perampanel during the OLEx; patients who received perampanel during the Double-blind Phase continued on perampanel during the OLEx. Efficacy and safety assessments across the Perampanel Treatment Duration were split by 52-week intervals (for ≤4 years) and included median percent change in SG or PGTC seizure frequency per 28 days, SG or PGTC 50% and 75% responder and seizure-freedom rates, and monitoring of treatment-emergent adverse events (TEAEs). Results: The Safety Analysis Set included 110 adolescent patients with SG seizures (mean age, 14.8 years; 40.0% female) and 19 adolescent patients with PGTC seizures (mean age, 15.1 years; 73.7% female). The mean (standard deviation) cumulative exposure to perampanel was 88.7 (63.8) weeks for SG seizures and 97.0 (35.5) weeks for PGTC seizures. Median percent reduction in SG or PGTC seizure frequency per 28 days and SG or PGTC 50% and 75% responder and seizure-freedom rates are shown in Table 1. For each seizure type, the overall incidence of TEAEs was highest during the first year of perampanel exposure and the most common TEAEs were dizziness, somnolence, and nasopharyngitis (Table 2). Conclusions: Based on this post hoc analysis, long-term (up to 4 years) adjunctive treatment with once-daily perampanel (≤12 mg/day) appeared to be efficacious and well tolerated in adolescent patients with GTC seizures. The safety and adverse-event profile was consistent with the double-blind studies. These post hoc results are encouraging given the refractory nature of GTC seizure types. Funding: Eisai Inc.