A randomized phase III trial of adjunctive zonisamide in pediatric patients with partial epilepsy

PURPOSE: To assess the efficacy and safety/tolerability of adjunctive zonisamide treatment in pediatric patients with partial epilepsy. METHODS: 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 (≥ 50% seizure frequency reduction from baseline) during the 12-week maintenance period. Safety/tolerability assessments included the incidence of treatment-emergent adverse events (TEAEs). KEY FINDINGS: 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 TEAEs 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%). TEAEs 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%). SIGNIFICANCE: Adjunctive zonisamide treatment was shown to be effective and well tolerated in pediatric patients with partial epilepsy. No new or unexpected safety findings emerged.