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--------------------------------------------------------------------------- JAMA Abstract - July 9, 1997 Safety and Efficacy of Pramipexole [Mirapex] in Early Parkinson Disease --------------------------------------------------------------------------- Context. Monotherapy with dopamine agonists may be useful in early Parkinson 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. University or academically based movement disorder clinics. Patients. A total of 264 patients with early Parkinson disease (PD) who were not requiring or receiving levodopa or other dopamine agonists were enrolled. Intervention. Subjects were randomized to 1 of 5 treatment groups: pramipexole doses of 1.5 mg/d, 3.0 mg/d, 4.5 mg/d, and 6.0 mg/d, or matching placebo. A 6-week dosage escalation period was followed by a 4-week maintenance period and a 1-week period during which active treatment was withdrawn. Main Outcome Measures. The primary measure of tolerability was the proportion of subjects completing the study on the assigned treatment. The primary measure of efficacy was the change from baseline to 10 weeks in the total score on the Unified Parkinson's Disease Rating 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 81% for the 1.5-mg/d, 92% for the 3.0-mg/d, 78% for the 4.5-mg/d, and 67% for the 6.0-mg/d treatment groups. There was a trend toward increased frequency of adverse experiences, particularly somnolence, in the 6.0-mg/d group. After 10 weeks of treatment, pramipexole-treated subjects showed a 20% improvement in total UPDRS scores, with mean improvements in scores ranging from 5.9 to 7.0 units among active treatment groups, compared with 0.9 units for the placebo group (P<.005 for each comparison with placebo). There was also evidence that the treatment effects were more pronounced in subjects with worse UPDRS scores at baseline. Conclusions. Pramipexole is safe and effective as short-term monotherapy in patients with early PD who are not receiving levodopa. Further study is warranted to determine the long-term impact of pramipexole on the progression of disability in PD and its value in comparison with levodopa therapy and other dopamine agonists. JAMA. 1997;278:125-130 -------------------------------------- A complete list of the Parkinson Study Group appears at the end of the article. Reprints: Karl Kieburtz, MD, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Ave, Box 673, Rochester, NY 14642. -------------------------------------- EDITOR'S NOTE. Pramipexole is a dopamine agonist that binds D2 receptor sites and is a promising new drug for Parkinson disease. Because adverse effects have limited the use of pramipexole, the Parkinson Study Group carried out a multicenter, placebo-controlled trial of 4 different dose schedules in 264 patients during 10 weeks. On average, there was a 20% clinical improvement. A total of 81% and 92% of patients receiving the 2 lowest doses and 78% and 67% of patients receiving the 2 highest doses completed the study. Adverse effects, particularly somnolence, were most common at the highest dose. The authors conclude that pramipexole is safe and effective as short-term monotherapy for patients with early Parkinson disease who are not receiving levodopa. Drummond Rennie, MD, Deputy Editor (West) --------------------------------------------------------------------------- Contents copyright 1997 American Medical Association. All rights reserved. --------------------------------------------------------------------------- [log in to unmask]