Efficacy of zonisamide against refractory partial seizures in an evaluable patient population

PURPOSE: To assess zonisamide efficacy in an evaluable population of patients with partial seizures receiving ³10 weeks' study medication during a 36-week, double-blind, placebo-controlled trial. METHODS: Following a 12-week baseline period, 351 patients (³12 years; receiving 1–3 antiepileptic drugs) were randomised (2:1:1:2) to placebo or zonisamide 100, 300 or 500mg/day. After a 6-week dose titration phase, patients entered an 18-week, fixed-dose phase. Responder rates (patients experiencing ³50% reduction in seizure frequency) and median percentage reduction in frequency of complex partial seizures (CPS), all partial and all seizures were assessed in an evaluable population, and adverse events (AEs) were assessed in all patients enrolled. RESULTS: 294 patients were included in the efficacy analysis. Zonisamide 500mg/day significantly reduced seizure frequency (49.8% vs 16.3%; p<0.001) and increased responder rates (50.0% vs 20.9%; p<0.001) for CPS, compared with placebo. The frequency of all partial and all seizures was also significantly reduced compared with placebo for zonisamide 300mg/day (p<0.01) and 500mg/day (p<0.0001). The responder rates with zonisamide 500mg/day were also statistically superior to placebo (p<0.001) for all partial (48.8% vs 19.8%) and all seizures (51.1% vs 18.3%). A significant linear relationship was observed between dose and responder rates for all seizures (p<0.0001). Zonisamide was well tolerated, although withdrawals due to AEs were greater with higher doses (6.7%, 0%, 12.5% and 24.6% for placebo, zonisamide 100, 300 and 500mg/day, respectively). The most common AEs were somnolence, dizziness, headache and nausea. CONCLUSION: Zonisamide is a well tolerated treatment that shows dose-dependent efficacy for refractoy partial epilepsy. Funded by Eisai Europe Ltd.