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 600 mg/day (200 mg 3 times daily), RTG/EZG 900 mg/day (300 mg 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 600 mg/day, n = 26; RTG/EZG 900 mg/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 600 mg/day and 17% with RTG/EZG 900 mg/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 900 mg/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.