Abstracts

Rationale: Retigabine is a first-in-class antiepileptic drug (AED) that reduces neuronal excitability by enhancing the activity of Kv7 potassium channels. Retigabine is an effective and generally well-tolerated adjunctive treatment under investigation for adult patients with partial-onset seizures. The potential for retigabine to provide freedom from seizures - the ultimate goal of epilepsy treatment - has been evaluated in two Phase III studies. Methods: The Retigabine Efficacy and Safety Trials for Partial Onset Epilepsy (RESTORE 1, Study 301; RESTORE 2, Study 302) were multicenter, randomized, double-blind, placebo-controlled, Phase III trials in adults with ≥4 partial-onset seizures per month during prospective baseline assessment while receiving stable doses of 1-3 additional AEDs with or without vagus nerve stimulation. Patients randomized to receive retigabine were titrated over 4 weeks to 600 or 900 mg/day (RESTORE 2) or over 6 weeks to 1200 mg/day (RESTORE 1) followed by a 12-week maintenance phase. Retigabine was administered TID. No dose reductions were permitted in the 600 or 900 mg/day treatment groups, but one dose reduction to 1050 mg/day was allowed in the 1200 mg/day treatment group at the start of the maintenance phase. The percentage of seizure-free days (defined as a day without any seizures) and proportion of seizure-free patients were assessed. Results: In RESTORE 1, the intent-to-treat (ITT) population totaled 305 patients (placebo, n=152; 1200 mg, n=153), and 256 (84%; placebo, n=137; 1200 mg, n=119) entered the maintenance phase. In RESTORE 2, the ITT population comprised 538 patients (placebo, n=179; 600 mg, n=181; 900 mg, n=178), and 471 (86%; placebo, n=164; 600 mg, n=158; 900 mg, n=149) entered the maintenance phase. The median percentage of seizure-free days during the double-blind treatment period (titration and maintenance) was significantly greater in each retigabine treatment group than placebo in both RESTORE studies (RESTORE 1: placebo = 77.3% versus 1200 mg/day = 84.1%, p<0.001; RESTORE 2: placebo = 77.8% versus 600 mg/day = 79.5%, 900 mg/day = 82.1%, p=0.021 and p<0.001, respectively). For patients who completed titration and entered the maintenance phase in RESTORE 1, significantly more patients were seizure-free with retigabine treatment compared with placebo during the maintenance phase (placebo = 1.5% [2/137] versus 1200 mg/day = 7.6% [9/119], p=0.027); this significant difference was not seen in RESTORE 2 (placebo = 1.2% [2/164], 600 mg/day = 3.2% [5/158], 900 mg/day = 4.7% [7/149], p=0.091 [900 mg versus placebo]).