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

Epilepsy Behav. 2016 Aug:61:224-230. doi: 10.1016/j.yebeh.2016.05.018. Epub 2016 Jul 1.

Abstract

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.

Keywords: Asian patients; Epilepsy; Ezogabine; Partial-onset seizures; Retigabine.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Carbamates / administration & dosage
  • Carbamates / adverse effects
  • Carbamates / therapeutic use*
  • Double-Blind Method
  • Drug Resistant Epilepsy / drug therapy*
  • Epilepsies, Partial / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenylenediamines / administration & dosage
  • Phenylenediamines / adverse effects
  • Phenylenediamines / therapeutic use*
  • Seizures / drug therapy*
  • Skin Pigmentation / drug effects
  • Treatment Outcome
  • Young Adult

Substances

  • Anticonvulsants
  • Carbamates
  • Phenylenediamines
  • ezogabine