Safety and efficacy of pramipexole in early Parkinson disease. A randomized dose-ranging study. Parkinson Study Group.

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escalation period was followed by a 4-week maintenance period and a 1-week period during which active treatment was withdrawn.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.