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. In the Retigabine Efficacy and Safety Trials for Partial Onset Epilepsy (RESTORE 1 and 2), retigabine 600, 900, and 1200 mg/day proved effective and was generally tolerated as adjunctive treatment for adult patients with partial-onset seizures. This report presents an analysis of the RESTORE 1 and 2 per-protocol populations. Methods: RESTORE 1 and 2 (Studies 301 [NCT00232596] and 302 [NCT00235755]) were multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials in adults with refractory epilepsy and ?4 partial-onset seizures per 28 days, receiving 1-3 AEDs, with or without vagus nerve stimulator. Patients were randomized to retigabine or placebo (administered tid) and underwent forced-titration to 600 or 900 mg/day (RESTORE 2) or 1200 mg/day (RESTORE 1) followed by a 12-week maintenance phase. One dose reduction to 1050 mg/day was allowed at the first maintenance phase visit in RESTORE 1. The changes in 28-day total partial-seizure frequency and responder rate (?50% reduction in baseline seizure frequency) from baseline to maintenance were assessed and analyzed for the per-protocol population, which included protocol completers without major protocol violations. Results: In RESTORE 1 and 2, 305 and 538 patients respectively, were randomized to retigabine or placebo and received ?1 dose of study drug (RESTORE 1: 1200 mg/day, n=153; placebo, n=152; RESTORE 2: 600 mg/day, n=181; 900 mg/day, n=178; placebo, n=179). The per-protocol populations for RESTORE 1 and 2 totaled 211 and 396, respectively (RESTORE 1: 1200 mg/day, n=89; placebo, n=122; RESTORE 2: 600 mg/day, n=130; 900 mg/day, n=117; placebo, n=149). In the RESTORE 1 per-protocol population, median reduction in seizure frequency from baseline to maintenance for retigabine 1200 mg/day vs placebo was 56.7% vs 20.0% (p<0.001), with responder rates to maintenance of 60.7% vs 21.3% (p<0.001). In the RESTORE 2 per-protocol population, median reduction in seizure frequency from baseline to maintenance for retigabine 600 and 900 mg/day vs placebo was 37.7% and 50.6%, vs 16.7% (p?0.001 each), with responder rates to maintenance of 38.5% and 50.4%, vs 18.8% (p<0.001 each). Although safety and tolerability were not assessed separately in the per-protocol populations, retigabine was generally well tolerated in the overall safety population as presented previously.