Abstracts

Rationale: Retigabine (referred to as ezogabine in North America) is a first-in-class antiepileptic drug (AED) that reduces neuronal excitability by enhancing the activity of KCNQ (Kv7) potassium channels. The potential for retigabine to provide freedom from seizures - the ultimate goal of epilepsy treatment - has been evaluated in a pooled analysis of 3 pivotal controlled trials. Methods: Study 205 (Phase IIb), and RESTORE 1 and 2 (Studies 301 [NCT00232596] and 302 [NCT00235755], Phase III) were multicenter, randomized, double-blind, placebo-controlled, parallel-group trials in adults with drug-resistant epilepsy, ?4 partial-onset seizures per 28 days, receiving 1-2 (Study 205) or 1-3 (RESTORE 1 and 2) AEDs, with or without vagus nerve stimulator. Patients were randomized to retigabine or placebo (administered tid) and underwent forced-titration to retigabine 600 or 900 mg/day (Study 205, RESTORE 2) or 1200 mg/day (Study 205, RESTORE 1) followed by an 8- (Study 205) or 12-week (RESTORE 1 and 2) maintenance phase. The percentage of seizure-free days (defined as a day without any seizures) and the proportion of seizure-free patients were assessed during the maintenance phase and double-blind period (titration and maintenance phases) in an integrated analysis of the 3 pivotal controlled trials. Results: Patients randomized to retigabine 600 (n=281) and 900 mg/day (n=273) were compared with placebo (n=275) in patients from Study 205 and RESTORE 2; 1200 mg/day (n=259) was compared with placebo (n=248) in patients from Study 205 and RESTORE 1. During both the maintenance phase and double-blind period, there were significant differences in the percentage of seizure-free days at all retigabine dose groups compared with placebo (Table 1). There were no significant differences in the proportion of seizure-free patients receiving retigabine 600 and 900 mg/day compared with placebo during either the maintenance phase or double-blind period, but there was a significant difference for retigabine 1200 mg/day vs placebo for both analysis periods (Table 2). Conclusions: In this analysis, retigabine 600-1200 mg/day was associated with improvement in the percentage of seizure-free days compared with placebo as adjunctive therapy in adults with partial-onset seizures. Furthermore, a significantly greater proportion of patients were seizure-free with retigabine 1200 mg/day compared with placebo. These results further validate the efficacy of retigabine in patients with refractory epilepsy. Funded by Valeant Pharmaceuticals International and GlaxoSmithKline.