The efficacy and safety / tolerability of adjunctive Zonisamide ( Zonegran ) treatment in pediatric patients with partial epilepsy, was assessed.
In this phase III, double-blind, randomized, placebo-controlled, multicenter trial, 207 patients ( age 6-17 years ) with partial epilepsy, receiving one or two antiepileptic drugs, were randomized to receive adjunctive Zonisamide or placebo.
Zonisamide was initiated at 1 mg/kg/day, titrated to a target dose of 8 mg/kg/day over 8 weeks ( one down-titration permitted ), and maintained for 12 weeks.
The primary efficacy end point was the proportion of responders ( greater than or equal to 50% seizure frequency reduction from baseline ) during the 12-week maintenance period.
Safety / tolerability assessments included the incidence of treatment-emergent adverse events ( TEAEs ).
In total, 93 ( 86.9% ) of 107 patients randomized to Zonisamide and 90 ( 90.0% ) of 100 patients randomized to placebo completed the trial.
Responder rates were 50% for Zonisamide versus 31% for placebo ( p = 0.0044; intention-to-treat population, last observation carried forward ).
The overall incidence of treatment-emergent adverse events was similar for Zonisamide ( 55.1% ) versus placebo ( 50.0% ), with low rates of serious TEAEs with Zonisamide and placebo ( 3.7% vs 2.0% ) and TEAEs leading to withdrawal ( 0.9% vs 3.0% ).
Treatment-emergent adverse events reported more frequently with Zonisamide versus placebo were decreased appetite ( 6.5% vs 4.0% ), decreased weight ( 4.7% vs 3.0% ), somnolence ( 4.7% vs 2.0% ), vomiting ( 3.7% vs 2.0% ), and diarrhea ( 3.7% vs 1.0% ).
In conclusion, adjunctive Zonisamide treatment was shown to be effective and well tolerated in pediatric patients with partial epilepsy.
No new or unexpected safety findings emerged. ( Xagena )
Guerrini R et al, Epilepsia 2013;54:1473-1480