Abstracts

Rationale: In a randomized, double-blind, phase III trial (study 305, ClinicalTrials.gov identifier: NCT00699582), perampanel, a non-competitive AMPA receptor antagonist, was efficacious as adjunctive therapy in patients with uncontrolled partial seizures, compared with placebo. Here we report an analysis of the efficacy of perampanel in combination with different numbers of concomitant antiepileptic drugs (AEDs) in study 305.Methods: Following a 6-week Baseline, patients aged ?12 years with refractory partial seizures were randomized (1:1:1) to receive once-daily Double-blind treatment (6 week Titration, 13 week Maintenance) with placebo, perampanel 8 mg or perampanel 12 mg. At Baseline, patients were on stable doses of 1-3 concomitant AEDs (only one a priori, protocol-defined CYP450-inducer AED was permitted). Seizure frequency was recorded in a daily diary and change in seizure frequency (Double-blind Phase vs Baseline) and responder rate (patients with ?50% reduction in seizure frequency in the Maintenance Period) were assessed in the Full Intent-To-Treat (Full ITT) analysis set (all patients who received study drug and had any seizure frequency data during the Double-blind Phase). Results: Of 389 patients randomized, 386 patients were included in the safety population and Full ITT analysis set. The mean time (years SD) since epilepsy diagnosis was similar across all treatment groups (22 13, 23 14 and 21 13 in placebo, perampanel 8 mg and perampanel 12 mg groups, respectively). Combined available data about baseline AEDs and prior AEDs confirmed that the patients who entered this study continued to have uncontrolled seizures despite receiving a mean of 3.17 AEDs over the past 5 years (3.07, 3.21 and 3.23, for placebo, perampanel 8 mg and perampanel 12 mg groups, respectively). At baseline, 10.9% of patients were taking one, 50.5% were taking two, and 38.6% were taking three concomitant AEDs. Patients receiving three AEDs are likely to represent those that are more refractory to treatment. The percentages of patients receiving the AEDs carbamazepine, oxcarbazepine, and phenytoin, which are known to induce perampanel clearance, were 34.5%, 18.7% and 7.5%, respectively, at baseline. Median percent changes in seizure frequency (Double-blind Phase vs Baseline) and responder rates (Maintenance Period vs Baseline) in patients taking one, two or three AEDs at Baseline for each group are shown in Table 1. No inferential analyses were performed for these study groups. Conclusions: The majority of patients in study 305 were taking two or three concomitant AEDs at Baseline. Perampanel was more effective than placebo in increasing responder rates in patients receiving one, two or three AEDs, and in increasing the median percent reduction in seizure frequency in patients receiving one or two AEDs. Median percent reduction in seizure frequency was greater than placebo for patients on three AEDs in the perampanel 8 mg group, and was similar to placebo in the 12 mg group. Support: Eisai Inc.