A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease.

BACKGROUND Treatment with rasagiline mesylate, an irreversible monoamine oxidase type B inhibitor, improves symptoms of early Parkinson disease (PD). Preclinical studies suggest that this compound may also modify the progression of PD. OBJECTIVE To compare the effects of early and later initiation of rasagiline on progression of disability in patients with PD. DESIGN Double-blind, parallel-group, randomized, delayed-start clinical trial. SETTINGS AND PATIENTS Four hundred four subjects with early PD, not requiring dopaminergic therapy, enrolled at 32 sites in the United States and Canada. INTERVENTIONS Subjects were randomized to receive rasagiline, 1 or 2 mg/d, for 1 year or placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months. MAIN OUTCOME MEASURE Change in total Unified Parkinson's Disease Rating Scale score from baseline to 12 months. RESULTS Three hundred seventy-one subjects were included in the 1-year efficacy analysis. Subjects treated with rasagiline, 2 mg/d, for 1 year had a 2.29-unit smaller increase in mean adjusted total Unified Parkinson's Disease Rating Scale score compared with subjects treated with placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months (P =.01). The mean adjusted difference between the placebo/rasagiline, 2 mg/d, group and those receiving rasagiline, 1 mg/d, for 1 year was -1.82 unit on the Unified Parkinson's Disease Rating Scale score (P =.05). CONCLUSION Subjects treated with rasagiline, 2 and 1 mg/d, for 12 months showed less functional decline than subjects whose treatment was delayed for 6 months.