Efficacy and safety of retigabine/ezogabine as adjunctive therapy in adult Asian patients with drug-resistant partial-onset seizures: A randomized, placebo-controlled Phase III study

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of adjunctive retigabine/ezogabine (RTG/EZG) therapy in Asian adults with partial-onset seizures. METHODS: A Phase III, randomized, double-blind, placebo-controlled, parallel-group study was conducted at 26 centers in Asia. Eligible patients were randomized in a 1:1:1 ratio to receive RTG/EZG 600mg/day (200mg 3 times daily), RTG/EZG 900mg/day (300mg 3 times daily), or placebo. The study consisted of an 8-week screening/baseline phase, followed by a 16-week treatment phase (4-week titration phase and 12-week maintenance phase). RESULTS: The study was terminated early because of emerging safety information on RTG/EZG (i.e., retinal pigmentation and skin/mucosal discoloration) from long-term trials. Of 132 patients screened and 76 randomized, 75 (placebo, n=25; RTG/EZG 600mg/day, n=26; RTG/EZG 900mg/day, n=24) received at least 1 dose of the study drug and were included in the safety and intent-to-treat populations. The responder rate (≥50% reduction in 28-day total partial-onset seizure frequency) was 31% with RTG/EZG 600mg/day and 17% with RTG/EZG 900mg/day versus 0% with placebo. Median percent change from baseline in 28-day total partial-onset seizure frequency during the maintenance phase was -33.90% and -22.46% with RTG/EZG 600 and 900mg/day, respectively, versus -22.21% with placebo. No new safety concerns were identified. CONCLUSIONS: Insufficient data were obtained to permit definitive conclusions. However, the results appear to be broadly in line with those from previous studies that included primarily Caucasian patients.