Abstracts

Rationale: Perampanel (E2007) is a selective, non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist that was effective in several animal seizure models. Perampanel was well tolerated in preliminary Phase II trials and is being evaluated as an add-on therapy for patients with refractory partial seizures in a Phase III program. This report describes the results of the first large multinational Phase III randomized, placebo-controlled trial demonstrating the efficacy and safety of perampanel (2-8 mg/day) as add-on therapy for refractory partial seizures.Methods: Subjects were 12-72 yrs old with partial seizures with/without secondary generalized seizures treated with 1-3 concomitant AEDs. Subjects were randomized to treatment with once-daily perampanel 2, 4, or 8 mg/day, or to placebo. Following a 6-week Baseline Phase, patients entered a 19-week Treatment Phase (6-week titration and 13-week maintenance). The primary endpoint was median percentage change in 28-day seizure frequency in the Maintenance Period relative to Pre-randomization. Secondary endpoints included responder rate (subjects with at least 50% reduction in seizure frequency during Maintenance Phase relative to Pre-randomization). Safety and tolerability were secondary objectives. Results: 712 subjects (49% male; 65% Caucasian; mean age 34 yrs) were randomized in 25 countries in Europe and Asia-Pacific regions to treatment with 2 mg (n=180), 4 mg (n=174), and 8 mg (n=171) perampanel/day, or to placebo (n=187). Median seizure frequency change for the ITT population was -16.3% (p=ns), -28.6% (p=0.003), and -33.5% (p<0.001) in the 2, 4, and 8 mg perampanel/day groups, respectively, versus -13.8% with placebo. Responder rates were 20.9% (