Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of ezogabine (United States adopted name)/retigabine (international nonproprietary name) (EZG[RTG]) 1,200 mg/day as adjunctive treatment in adults with drug-resistant epilepsy with partial-onset seizures with or without secondary generalization.

METHODS:

RESTORE 1 was a multicenter, randomized, double-blind, parallel-group trial. Following a prospective 8-week baseline phase, patients entered an 18-week double-blind treatment period (6-week forced dose titration to EZG[RTG] 1,200 mg/day in 3 equally divided doses or placebo, followed by a 12-week maintenance phase). Results were analyzed on an intent-to-treat basis for the entire 18-week period and for patients reaching the maintenance phase.

RESULTS:

In 306 patients randomized, 305 received EZG(RTG) 1,200 mg/day (n = 153) or placebo (n = 152). Median percent reduction in total partial-seizure frequency was 44.3% vs 17.5% (p < 0.001) for EZG(RTG) and placebo, respectively, during the 18-week double-blind period; responder rates (≥50% reduction in total partial-seizure frequency from baseline) were 44.4% vs 17.8% (p < 0.001). In 256 patients (EZG[RTG], 119; placebo, 137) entering the 12-week maintenance phase, median percent reduction in seizure frequency for EZG(RTG) vs placebo was 54.5% and 18.9% (p < 0.001), respectively; responder rates were 55.5% vs 22.6% (p < 0.001). The proportion of patients discontinuing due to treatment-emergent adverse events (TEAEs) was 26.8% (EZG[RTG]) vs 8.6% (placebo). Dizziness, somnolence, fatigue, confusion, dysarthria, urinary tract infection, ataxia, and blurred vision were the most common TEAEs reported by more patients treated with EZG(RTG) than placebo.

CONCLUSIONS:

This study demonstrates that EZG(RTG) is effective as add-on therapy for reducing seizure frequency in patients with drug-resistant partial-onset seizures.

CLASSIFICATION OF EVIDENCE:

This study provides Class II evidence that EZG(RTG) 1,200 mg/day is effective as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization.

• Authors: J A French, B W Abou-Khalil, R F Leroy, E M T Yacubian, P Shin, S Hall, H Mansbach, V Nohria, RESTORE 1/Study 301 Investigators
• Journal: Neurology (Neurology) Vol. 76 Issue 18 Pg. 1555-63 (May 03 2011) ISSN: 1526-632X [Electronic] United States
• PMID: 21451152 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Carbamates
• Phenylenediamines
• ezogabine

Topics

• Adolescent
• Adult
• Aged
• Anticonvulsants (administration & dosage, adverse effects, therapeutic use)
• Carbamates (administration & dosage, adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Epilepsies, Partial (drug therapy)
• Female
• Humans
• Male
• Middle Aged
• Phenylenediamines (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome