Oxcarbazepine placebo-controlled, dose-ranging trial in refractory partialepilepsy

Purpose: The goal of the study was to evaluate the safety and efficacy of a broad oxcarbazepine (OXC) dosage range (600, 1200, and 2400 mg/d) as adjun ctive therapy for uncontrolled partial seizures and to determine the relati onship between trough plasma 10-monohydroxy derivative concentrations and O XC safety and efficacy. Methods: This multinational, multicenter, randomized, 28-week, double-blind , placebo-controlled, four-arm, parallel-group trial enrolled 694 patients aged 15-65 years with uncontrolled partial seizures with or without seconda rily generalized seizures. The primary efficacy variable was percentage cha nge in seizure frequency per 28 days relative to baseline. Results: The median reduction in seizure frequency was 26%, 40%, 50%, or 8% for patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectivel y (alI p less than or equal to 0.0001). Of patients in the 600, 1200, or 24 00 mg/d OXC groups, 27%, 42%, and 50% respectively, had more than 50% reduc tion in seizure frequency compared with 13% for placebo (all p < 0.001). Hi gher plasma 10-monohydroxy derivative concentrations were associated with l arger decreases in seizure frequency (p = 0.0001). During the double-blind treatment phase, 84%, 90%, 98%, and 76% of patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively, reported one or more adverse event s. The most common adverse events were related to the nervous and digestive systems. Conclusions: OXC is safe and effective as adjunctive therapy in patients wi th uncontrolled partial seizures. OXC 600 mg/d was the minimum effective do sage; effectiveness of OXC increased with dose. The rapid and fixed titrati on to high doses was associated with an increased risk of adverse events, w hich could potentially be reduced by adjusting concomitant antiepileptic me dication and by using a slower, flexible OXC titration schedule.