Efficacy and tolerability of zonisamide versus controlled-release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomised, double-blind, non-inferiority trial

Abstract

Background Additional options are needed for monotherapy treatment of adults newly diagnosed with partial epilepsy. This trial compares the efficacy and tolerability of once-daily zonisamide with twice-daily controlled-release carbamazepine monotherapy for such patients. Methods In this phase 3, randomised, double-blind, parallel-group, non-inferiority trial, adults from 120 centres in Asia, Australia, and Europe, aged 18-75 years and newly diagnosed with partial epilepsy, were randomly assigned (in a 1:1 ratio, done with a computer-generated pseudorandom code) to receive zonisamide or carbamazepine. Patients, investigators, and sponsor personnel giving drugs, analysing outcomes, and interpreting data were masked to treatment allocation. After treatment initiation (zonisamide 100 mg/day vs carbamazepine 200 mg/day [given in two doses]) and up-titration (to 300 mg/day vs 600 mg/day), patients entered a 26-78 weeks flexible-dosing period (200-500 mg/day vs 400-1200 mg/day, according to response and tolerance). Once patients were seizure-free for 26 weeks they entered a 26-week maintenance phase. The primary endpoint was the proportion of patients who achieved seizure freedom for 26 weeks or more in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT00477295. Findings 583 patients were randomly assigned to treatment groups (282 zonisamide, 301 carbamazepine), of whom 456 were analysed for the primary endpoint (per-protocol population: 223 zo…