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

Background: Preclinical evidence suggests that manipulation of the glutamat ergic system may provide an alternative strategy for therapeutic interventi on in PD. Remacemide hydrochloride is a low affinity NMDA channel blocker t hat might improve parkinsonian symptoms by modulating glutamatergic overact ivity in the basal ganglia or slow worsening by decreasing excitotoxicity. Methods: The authors performed a multicenter, randomized, double-blind, pla cebo-controlled, parallel-group, dose-ranging study of remacemide in patien ts 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 remacem ide 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 schedu le. 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 evi dence of improvement in PD signs or symptoms associated with remacemide mon otherapy. Conclusion: Remacemide was generally well tolerated and safe in t his 5-week trial. There was no evidence for a symptomatic effect of remacem ide monotherapy in patients with early PD. Based on its favorable safety pr ofile and several animal studies, further studies of remacemide are warrant ed as symptomatic therapy in levodopa-treated patients and as a neuroprotec tive agent.