A multicenter randomized controlled trial of remacemide hydrochloride as monotherapy for PD

Background: Preclinical evidence suggests that manipulation of the glutamatergic system may provide an alternative strategy for therapeutic intervention in PD. Remacemide hydrochloride is a low affinity NMDA channel blocker that might improve parkinsonian symptoms by modulating glutamatergic overactivity in the basal ganglia or slow worsening by decreasing excitotoxicity. Methods: The authors performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of remacemide in patients with early PD who were not yet receiving levodopa or dopamine agonists. The primary objective was to assess the short-term tolerability and safety of three dosage levels of remacemide. Two hundred patients were randomized to receive either remacemide 150 mg, 300 mg, or 600 mg, or matching placebo daily for 5 weeks. Results: Significantly fewer patients receiving remacemide 600 mg daily were able to tolerate 5 weeks of their assigned treatment on a BID schedule compared with patients receiving placebo (64% versus 94%,p = 0.0002). Most patients who experienced intolerable side effects on the BID schedule, however, could tolerate the same daily dosage on a QID schedule. The most common adverse events were dizziness and nausea. There were no serious adverse events or clinically significant treatment-related changes in vital signs, laboratory values, or electrocardiograms. There was no evidence of improvement in PD signs or symptoms associated with remacemide monotherapy. Conclusion: Remacemide was generally well tolerated and safe in this 5-week trial. There was no evidence for a symptomatic effect of remacemide monotherapy in patients with early PD. Based on its favorable safety profile and several animal studies, further studies of remacemide are warranted as symptomatic therapy in levodopa-treated patients and as a neuroprotective agent.