Remacemide hydrochloride is a low-affinity, non-competitive
N-methyl-D-aspartic acid (
NMDA) receptor channel blocker, under investigation in
epilepsy. This double-blind, placebo-controlled, multicentre study assessed the safety and efficacy of
remacemide hydrochloride or placebo, as adjunctive
therapy, in 252 adult patients with
refractory epilepsy who were already taking up to three
antiepileptic drugs (including an
enzyme-inducer). Patients were randomized to one of three doses of
remacemide hydrochloride (300, 600 or 1200 mg /day) or placebo Q.I.D., for up to 15 weeks. An increasing percentage of responders (defined as a reduction in seizure frequency from baseline of > or =50%) was seen with increasing
remacemide hydrochloride dose. At 1200 mg /day, 23% of patients were responders compared with 7% on placebo. This difference was significant (P = 0.016), as was the overall difference between treatments (P = 0.038). Adverse events:
dizziness, abnormal gait, gastrointestinal disturbance,
somnolence,
diplopia and
fatigue were mild or moderate in severity.
Carbamazepine and
phenytoin plasma concentrations were well controlled and maintained within target ranges, with no evidence of improved seizure control due to increases in the concentrations of these drugs. A dose-dependent, significant, increase in responders following adjunctive
remacemide hydrochloride compared with placebo was observed.
Remacemide hydrochloride was well tolerated.