A randomized,double-blind,placebo-controlled,multicenter study to evaluate the efficacy and safety of zonisamide as adjunctive treatment in patients with refractory partial seizures

Abstract

Objective To evaluate the safety and efficacy of Zonisamide(ZNS) as adjunctive therapy in patients with refractory partial seizures receiving other antiepileptic drags (AEDs).Methods This was a randomized,double-blind,placebo-controlled study conducted at multi-centers.All 240 subjects were randomized to either the ZNS group or the placebo group in a 1:1 ratio.The double-blind treatment phase included a titration phase during which zonisamide dose inereased from 100 mg/day to 300 mg/day over 4 weeks and then a 12-week fixed-dose phase.The primary efficacy endpoint was,the median % reduction from baseline in all pattial seizure frequency(CPS+SPS+SGS)during the fixed-dose phase.The important secondaw endpoint wag the responder rate.Safety profiles and tolerance were also evaluated.Results The FAS analysis showed the median reduction from baseline in the ZNS group was greater than in the placebo group(48.4%vs 26.6%),the difference was significant for ZNS compared with placebo(F=4.904,P=0.028);The responder rates for all partial seizures(48.6%vs34.9%,X2=4.046,P=0.044)and for complex seizures(52.2% vs 33.3%,X2=5.607,P=0.018)were significantly higber in the ZNS group than in the placebo group in the FAS population.The overall adverse events(AEs)profile was comparable between the two groups.The most frequent AEs considered to be related to zonisamide by the investigator were headache,dizziness,somnolence,anorexia,nausea,etc.Conclusions ZNS is superior to placebo in reducing the frequency of partial seizures and well-tolerated.ZNS could be a choice of adjunctive therapy in patients with refractory partial seizures. Key words: Epilepsies,partial; Isoxazoles; Randomized controlled trial