Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy.

Abstract

OBJECTIVE:

This study assessed the efficacy and safety of the neuronal potassium channel opener ezogabine (US adopted name; EZG)/retigabine (international nonproprietary name; RTG) as adjunctive therapy for refractory partial-onset seizures.

METHODS:

This was a multicenter, randomized, double-blind, placebo-controlled trial in adults with ≥4 partial-onset seizures per month receiving 1 to 3 antiepileptic drugs. EZG (RTG) or placebo, 3 times daily, was titrated to 600 or 900 mg/d over 4 weeks, and continued during a 12-week maintenance phase. Median percentage seizure reductions from baseline and responder rates (≥50% reduction in baseline seizure frequency) were assessed.

RESULTS:

The intention-to-treat population comprised 538 patients (placebo, n = 179; 600 mg, n = 181; 900 mg, n = 178), 471 of whom (placebo, n = 164; 600 mg, n = 158; 900 mg, n = 149) entered the maintenance phase. Median percentage seizure reductions were greater in EZG (RTG)-treated patients (600 mg, 27.9%, p = 0.007; 900 mg, 39.9%, p < 0.001) compared with placebo (15.9%). Responder rates were higher in EZG (RTG)-treated patients (600 mg, 38.6%, p < 0.001; 900 mg, 47.0%, p < 0.001) than with placebo (18.9%). Treatment discontinuations due to adverse events (AEs) were more likely with EZG (RTG) than with placebo (placebo, 8%; 600 mg, 17%, 900 mg, 26%). The most commonly reported (>10%) AEs in the placebo, EZG (RTG) 600 mg/d, and EZG (RTG) 900 mg/d groups were dizziness (7%, 17%, 26%), somnolence (10%, 14%, 26%), headache (15%, 11%, 17%), and fatigue (3%, 15%, 17%).

CONCLUSIONS:

In this dose-ranging, placebo-controlled trial, adjunctive EZG (RTG) was effective and generally well tolerated in adults with refractory partial-onset seizures.

CLASSIFICATION OF EVIDENCE:

This study provides Class II evidence that adjunctive EZG/RTG reduces the occurrence of partial-onset seizures.

• Authors: M J Brodie, H Lerche, A Gil-Nagel, C Elger, S Hall, P Shin, V Nohria, H Mansbach, RESTORE 2 Study Group
• Journal: Neurology (Neurology) Vol. 75 Issue 20 Pg. 1817-24 (Nov 16 2010) ISSN: 1526-632X [Electronic] United States
• PMID: 20944074 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Carbamates
• Phenylenediamines
• ezogabine

Topics

• Adult
• Anticonvulsants (administration & dosage, adverse effects)
• Carbamates (administration & dosage, adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Therapy, Combination
• Epilepsies, Partial (diagnosis, drug therapy)
• Female
• Humans
• Male
• Middle Aged
• Outcome Assessment, Health Care
• Phenylenediamines (administration & dosage, adverse effects, therapeutic use)
• Prospective Studies
• Treatment Outcome