SAFETY AND EFFICACY OF PRAMIPEXOLE IN EARLY PARKINSON DISEASE - A RANDOMIZED DOSE-RANGING STUDY

Context.-Monotherapy with dopamine agonists may be useful in early Par kinson disease. Objective.-To evaluate dose-response relationships for tolerability, safety, and efficacy of the synthetic dopamine agonist pramipexole. Design.-Multicenter, multidosage, parallel-group, double- blind, placebo-controlled, randomized clinical trial. Setting.-Univers ity or academically based movement disorder clinics. Patients.-A total of 264 patients with early Parkinson disease (PD) who were not requir ing or receiving levodopa or other dopamine agonists were enrolled. In tervention.-Subjects were randomized to 1 of 5 treatment groups: prami pexole doses of 1.5 mg/d, 3.0 mg/d, 4.5 mg/d, and 6.0 mg/d, or matchin g placebo. A 6-week dosage escalation period was followed by a 4-week maintenance period and a 1-week period during which active treatment w as withdrawn. Main Outcome Measures.-The primary measure of tolerabili ty was the proportion of subjects completing the study on the assigned treatment. The primary measure of efficacy was the change from baseli ne to 10 weeks in the total score on the Unified Parkinson's Disease R ating Scale (UPDRS). Results.-Pramipexole was generally safe and well tolerated in this 10-week study. The proportion of subjects completing the study on the originally assigned dosage was 98% for placebo and 8 1% for the 1.5-mg/d, 92% for the 3.0-mg/d, 78% for the 4.5-mg/d, and 6 7% for the 6.0-mg/d treatment groups. There was a trend toward increas ed frequency of adverse experiences, particularly somnolence, in the 6 .0-mg/d group. After 10 weeks of treatment, pramipexole-treated subjec ts showed a 20% improvement in total UPDRS scores, with mean improveme nts in scores ranging from 5.9 to 7.0 units among active treatment gro ups, compared with 0.9 units for the placebo group (P<.005 for each co mparison with placebo). There was also evidence that the treatment eff ects were more pronounced in subjects with worse UPDRS scores at basel ine. Conclusions.-Pramipexole is safe and effective as short-term mono therapy in patients with early PD who are not receiving levodopa. Furt her study is warranted to determine the long-term impact of pramipexol e on the progression of disability in PD and its value in comparison w ith levodopa therapy and other dopamine agonists.