Abstracts

Rationale: AMPA receptors in the thalamocortical tract are hypothesized as key to initiation and propagation of generalized seizures. Perampanel, a selective non-competitive AMPA receptor antagonist, has been studied in pts with partial seizures with or without SG. Pooled analyses from Phase III, randomized, double-blind, placebo‑controlled studies (304, 305, and 306) demonstrated perampanel’s efficacy in SG seizures (Table 1).1 Perampanel has also been investigated in a Phase III, randomized, double‑blind, placebo‑controlled study (332) of idiopathic generalized epilepsy and uncontrolled PGTC seizures; adjunctive perampanel improved seizure control (Table 1).2 Our post‑hoc analysis evaluated efficacy and tolerability of perampanel across all four phase III studies in pts with SG or PGTC seizures.Methods: All studies involved pts aged ≥12 years. Studies 304 (n=388) and 305 (n=386) evaluated perampanel 8 or 12 mg/day or placebo. Study 306 (n=706) evaluated perampanel 2, 4, or 8 mg/day or placebo. These studies had a 19-week double-blind phase (6-week Titration and 13-week Maintenance Period). Study 332 (n=164) evaluated perampanel up to 8 mg/day or placebo (17-week double-blind phase; 4-week Titration, 13-week Maintenance Period). The Full Analysis Set (FAS) included pts from these phase III studies who had SG or PGTC seizures and received perampanel 8 mg/day.Results: The FAS evaluated 492 pts who had received 1 (n=107), 2 (n=232), or 3 (n=152) antiepileptic drugs (AEDs) at baseline; 1 placebo pt had received 4 concomitant AEDs, one was a rescue benzodiazepine as allowed by the protocol. Pts were randomized to perampanel 8 mg/day or placebo (mean age 31.7 years; ≥18 to <65 years 85.4%; male 48.4%; white 68.7%). Median PGTC/SG baseline seizure frequency per 28 days was 3.2 (0.6, 169.4) for placebo and 2.9 (0.6, 158.7) for perampanel. During treatment, these dropped to 2.5 (0.0, 121.7) and 1.0 (0.0, 67.0), respectively. Overall and compared with placebo, perampanel conferred a greater median percent reduction in PGTC/SG seizure frequency per 28 days (-24.6 vs -65.5; p<0.0001) and was associated with a greater 50% responder rate (37.8% vs 61.8%; p<0.0001). In the FAS, 12.6% of pts on placebo achieved seizure-free status from PGTC/SG, compared with 26.9% of pts receiving perampanel; pts who were not study completers were considered not to have achieved seizure-free status. Treatment-emergent adverse events (AEs) were experienced by 67.5% of pts for placebo and 79.9% of pts for perampanel. Compared with placebo, most common AEs with perampanel were dizziness (5.9% vs 28.6%, respectively), somnolence (5.9% vs 13.4%), and headache (10.6% vs 12.2%).Conclusions: Perampanel reduced generalized tonic-clonic seizure frequency, whether primary or SG. Treatment with perampanel was well tolerated. Funding: This study was funded by Eisai Inc. References 1. Steinhoff et al. Epilepsia 2013;54:1481-1489 2. French et al. Epilepsy Currents 2015;15(s1):367 abs 2.389