Extended-release pramipexole in early Parkinson disease: a 33-week randomized controlled trial.

Abstract

OBJECTIVE:

To assess the clinical efficacy of a novel once-daily extended-release (ER) formulation of the dopamine agonist pramipexole as monotherapy in patients with early Parkinson disease (PD) and establish its noninferiority vs standard immediate-release (IR) pramipexole.

METHODS:

This was a multicenter, double-blind, parallel study of patients with early PD not receiving levodopa or dopamine agonists, randomly assigned to pramipexole IR, pramipexole ER, or placebo. Seven-week flexible titration was followed by 26-week maintenance, with levodopa permitted as rescue medication. The primary analysis was to test pramipexole ER noninferiority to pramipexole IR based on a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 33 weeks, with noninferiority predefined as a treatment group difference for which the lower bound of the 95% confidence interval (CI) did not exceed -3 points.

RESULTS:

Among 213 ER and 207 IR recipients, the adjusted mean 33-week UPDRS II+III change (excluding levodopa rescue effects) was -8.2 for ER and -8.7 for IR, a difference of -0.5 with a 95% CI of -2.3 to 1.3. Compared with placebo (n = 103), pramipexole ER and pramipexole IR were significantly superior on UPDRS II+III score, all key secondary outcomes, and almost all other endpoints. On the 39-item Parkinson Disease Questionnaire, superiority of pramipexole ER failed to reach statistical significance. Both formulations were equally safe and well-tolerated.

CONCLUSIONS:

As monotherapy for early PD, pramipexole ER was noninferior to pramipexole IR and significantly more effective than placebo. Tolerability and safety did not differ between the formulations.

CLASSIFICATION OF EVIDENCE:

This study provides Class I evidence that pramipexole ER is not inferior to pramipexole IR in patients with early PD.

• Authors: W Poewe, O Rascol, P Barone, R A Hauser, Y Mizuno, M Haaksma, L Salin, N Juhel, A H V Schapira, Pramipexole ER Studies Group
• Journal: Neurology (Neurology) Vol. 77 Issue 8 Pg. 759-66 (Aug 23 2011) ISSN: 1526-632X [Electronic] United States
• PMID: 21832218 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• Benzothiazoles
• Pramipexole

Topics

• Aged
• Analysis of Variance
• Antiparkinson Agents (therapeutic use)
• Benzothiazoles (therapeutic use)
• Double-Blind Method
• Drug Administration Schedule
• Drug Delivery Systems
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Parkinson Disease (drug therapy)
• Pramipexole
• Severity of Illness Index
• Surveys and Questionnaires
• Time Factors
• Treatment Outcome