Abstracts

Rationale: Perampanel, a selective, non-competitive AMPA receptor antagonist, is approved for adjunctive treatment of partial seizures, with or without secondary generalized (SG) seizures, and for primary generalized tonic-clonic seizures (PGTCS) in patients with epilepsy aged ?-12 years. In Phase II/III randomized, double-blind, placebo-controlled studies, adjunctive perampanel (up to 12 mg/day) demonstrated efficacy and tolerability in patients with partial seizures with or without SG seizures (studies 206 [NCT00144690], 208 [NCT00416195], 304 [NCT00699972], 305 [NCT00699582], 306 [NCT00700310], and 335 [NCT01618695]), and in patients with idiopathic generalized epilepsy and uncontrolled PGTCS (study 332 [NCT01393743]). Patients who completed these studies were eligible to enter the OLE studies 207 (NCT00368427; studies 206 and 208) and 307 (NCT00735397; studies 304, 305, and 306), or the OLE Phases of studies 335 and 332. Here, we report post-hoc analyses of pooled long-term efficacy and safety outcomes in patients with generalized tonic-clonic (GTC) seizures (whether SG or PGTC) across the four OLE studies. Methods: All OLE studies consisted of a blinded Conversion Period (6?"16 weeks across studies), where perampanel dose optimization was achieved (maximum 12 mg/day), followed by a Maintenance Phase (32?"424 weeks; =1 to =8 years' exposure, across studies). Patients who had previously received placebo during the Double-blind Phase were converted to perampanel during the OLE; patients who had previously received perampanel during the Double-blind Phase continued on perampanel during the OLE. Efficacy assessments across the OLE Treatment Phase included percent change in seizure frequency per 28 days, and 50%, 75%, and 100% responder rates. Safety assessments included monitoring treatment-emergent adverse events (TEAEs), discontinuations, and dose adjustments, withdrawals, reductions, or interruptions. Results: The full analysis set included 858 patients (SG seizures, n=720; PGTCS, n=138): mean age 31.7 years and 50.2% female. The mean cumulative exposure to perampanel, median percent change in seizure frequency, and 50%, 75%, and 100% responder rates across the OLE Treatment Phase are shown in Table 1. For each seizure type, an improvement in efficacy from baseline was observed irrespective of treatment received during the Double-blind Phase. The overall incidence of TEAEs reported in the safety analysis set are shown in Table 2. In the pooled population, the most common TEAEs in patients with GTC seizures were dizziness (43.4%), somnolence (19.6%), nasopharyngitis (15.4%), headache (14.9%), weight increase (11.8%), irritability (11.0%), and fatigue (10.8%). Conclusions: Long-term adjunctive treatment with perampanel demonstrated efficacy in patients with GTC seizures, whether SG or PGTCS, irrespective of prior treatment during the Double-blind Phase of the study. Safety outcomes were consistent with the known safety profile of perampanel. Funding: Eisai Inc.