Abstracts

Rationale: A longer duration of epilepsy has been associated with the risk of drug-resistant epilepsy and thus may be an important factor to consider when choosing AED treatments.1,2 Perampanel (PER), a selective noncompetitive AMPA receptor antagonist with a novel mechanism of action, is approved in >40 countries for adjunctive treatment of partial seizures, with or without secondarily generalized seizures, in patients with epilepsy aged ≥12 yrs. This analysis reports efficacy results of PER adjunctive therapy in subjects with drug-resistant partial seizures stratified by duration of epilepsy.Methods: Subjects with refractory partial seizures enrolled in the 3 Phase III studies were ≥12 yrs old and receiving 1-3 concomitant AEDs. After a 6-wk baseline phase, subjects were randomized to 19 wks of once-daily double-blind (DB) treatment (6-wk titration, 13-wk maintenance) with placebo (PBO) or PER 8 or 12mg (Studies 304&305); or with PBO or PER 2, 4 or 8mg (Study 306). Data from these studies were pooled for this post hoc analysis, and efficacy of PBO as well as each PER dose group were analyzed by duration of epilepsy (subjects with time since diagnosis of partial seizures of ≤20yrs vs. >20yrs [based on mean time since diagnosis]). Efficacy endpoints for overall partial seizures in this analysis included median percent reduction from baseline in seizure frequency/28 days and responder rate (subjects who experienced ≥50% reduction in seizure frequency relative to baseline in the maintenance-LOCF).Results: In the overall pooled Phase III population, mean age was 34.9yrs, 51.4% of subjects were female, and mean time since partial seizures diagnosis was 21.3yrs. The efficacy population (full intent-to-treat analysis set) included 766 subjects with epilepsy duration ≤20yrs and 709 with duration >20yrs. During the DB phase relative to baseline, reduction in seizure frequency/28 days was observed in subjects whose epilepsy duration was ≤20yrs (median percent reduction for PBO: 11.8%, PER 2mg: 9.9%, 4mg: 21.4%, 8mg: 30.5%, 12mg: 30.4%; total PER: 22.6%) and >20yrs (PBO: 14.6%; PER 2mg: 17.3%, 4mg: 28.4%, 8mg: 28.8%, 12mg: 24.7%; total PER: 26.3%) [95% confidence interval (CI) of difference between epilepsy duration ≤20yrs and >20yrs among PBO subjects: -6.2, 10.6; among total PER subjects: -2.2, 9.0] (Fig 1). Responder rates were greater with PER therapeutic doses (4-12mg) than with PBO for subjects with epilepsy duration of ≤20yrs [PBO: 44 (19.3%), PER 2mg: 16 (16.2%), 4mg: 28 (27.5%), 8mg: 77 (35.2%), 12mg: 45 (38.1%), total PER: 166 (30.9%)] and >20yrs [PBO: 41 (19.2%), PER 2mg: 21 (25.9%), 4mg: 21 (30.4%), 8mg: 75 (35.5%), 12mg: 43 (31.9%), total PER: 160 (32.3%)] (Fig 2). A limitation is that this is a post hoc analysis, and thus is not powered to show significance between epilepsy duration groups.Conclusions: In subjects with drug-resistant epilepsy, adjunctive PER 4, 8, and 12mg reduced the occurrence of seizures, regardless of shorter (≤20yrs) or longer (>20yrs) epilepsy duration. 1Luciano.AnnNeurol.2007;62:375 2Schiller.Neurol.2008;70:54 Support: Eisai Inc.