A placebo-controlled, double-blind cross-over trial of adjunctive one month remacemide hydrochloride treatment in patients with refractory epilepsy

The efficacy, safety and pharmacokinetics of adjunctive remacemide hydrochl oride, a novel, low-affinity non-competitive NMDA receptor channel blocker, were investigated in 28 adult patients with refractory epilepsy. This was a randomized double-blind placebo-controlled cross-over study with five 4-w eek periods (baseline, treatment 1, washout, treatment 2, washout). Baseline median seizure frequency was reduced by 33% following adjunctive r emacemide hydrochloride 150 mg q.i.d. for 4 weeks compared with placebo (P = 0.041). Seizure frequency was reduced by greater than or equal to 50% in 30% of patients treated with remacemide hydrochloride compared with 9% on p lacebo. Mean plasma concentration of concomitant carbamazepine increased by approximately 15% following adjunctive remacemide hydrochloride. There was no correlation between increased plasma carbamazepine and reduced seizure frequency. Remacemide hydrochloride was well tolerated and only three patients withdre w due to adverse events (two remacemide hydrochloride, one placebo). Two pa tients died unexpectedly from their epilepsy during placebo treatment; both deaths were considered by the investigators to be unrelated to earlier rem acemide hydrochloride treatment. This first specific efficacy investigation with adjunctive remacemide hydro chloride demonstrated anticonvulsant effects in patients with refractory ep ilepsy. More extensive clinical investigation is justified. (C) 2000 BEA Tr ading Ltd.