Efficacy and Safety of Remacemide versus Carbamazepine in Newly Diagnosed Epilepsy: Comparison by Sequential Analysis

An international trial comparing remacemide hydrochloride with carbamazepine was undertaken in newly diagnosed epilepsy using a novel double-blind, parallel group, double triangular sequential design. Patients with two or more partial or generalized tonic-clonic seizures in the previous year were randomized to 600 mg daily of remacemide or carbamazepine. Subsequent dosage adjustments were allowed while maintaining the blind. The trial completed 20 months after initiation following the second interim analysis. Efficacy data on 449 patients showed carbamazepine to be significantly more effective than remacemide in preventing seizure recurrence (P = 0.003). Median time to first seizure after titration, the primary endpoint, was 112 days for remacemide and 306 days with carbamazepine. Time to second, third, and fourth seizures after randomization all significantly favored carbamazepine. Remacemide was shown unequivocally to be inferior to carbamazepine in this patient population. This study also establishes carbamazepine as a proven treatment for use in subsequent active control comparative trials.