Abstracts

Rationale: Gender-based differences in pharmacokinetics have been identified as sources of interindividual variability in clinical response for various drugs. However, females have often been underrepresented in clinical trials of antiepileptic drugs (AEDs) even though epilepsy prevalence does not differ according to gender. In recent years, greater emphasis has been placed on increasing female participation in AED trials, providing an opportunity to evaluate potential gender-related differences in clinical response. A Phase 2 double-blind, placebo-controlled, dose-ranging trial of retigabine (RGB) as adjunctive therapy in patients with partial-onset seizures showed significant differences favoring 900 and 1200 mg/day RGB over placebo in seizure frequency reduction and proportion of patients with clinically significant response. (Porter RJ et al. Neurology 2007;68:1197-1204) With a 50-50 male/female distribution in this study, response according to gender was analyzed.Methods: The study enrolled adults (16-70 yrs of age) meeting criteria for refractory epilepsy (>2 yrs since epilepsy diagnosis and failure of adequate trials of >2 AEDs alone or in combination) who had at least 4 partial-onset seizures despite stable doses of 1-2 AEDs during 8-wk prospective baseline phase. Patients were randomized to 16-wks double-blind treatment with 600, 900, or 1200 mg/day RGB (tid dosing) or placebo. The 300 mg/day starting dose was increased weekly in 150 mg/day increments over 8 wks. Dosages could be reduced 100 mg/day no more than two times during wks 6 and 8, with no further adjustments during the subsequent 8-wk maintenance phase.Results: Of 95 patients randomized to 900 mg/day RGB, 48 were male and 47 were female; of 106 patients randomized to 1200 mg/day RGB, 55 were male and 51 were female. Proportion of patients with >50% seizure reduction during the 16-wk double-blind and 8-wk maintenance periods (table) was significantly higher with 900 or 1200 mg/day RGB vs placebo (p<0.05), regardless of gender. Responder rate with 900 mg/day was 33% in men and 30% in women; with 1200 mg/day, responder rates were 31% and 35%, respectively. Differences between genders were not significant. With forced titration and limited dosage adjustments, the most common treatment-emergent adverse events were somnolence, dizziness, confusion, speech disorder, vertigo, tremor, memory difficulty, abnormal thinking, abnormal gait, paresthesia, and diplopia. Conclusions: RGB is effective as adjunctive therapy in reducing partial-onset seizure frequency. Treatment response is not significantly different in females vs. males.