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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. Neurology® 2011;77:759–766
GLOSSARY
- ADL=
- activities of daily living;
- AE=
- adverse event;
- ANCOVA=
- analysis of covariance;
- CI=
- confidence interval;
- DSM-IV=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
- EQ-5D=
- EuroQol-5D;
- ER=
- extended-release;
- ESS=
- Epworth Sleepiness Scale;
- FAS=
- full-analysis set;
- IR=
- immediate-release;
- LOCF=
- last observation carried forward;
- mMIDI=
- modified Minnesota Impulsive Disorders Interview;
- PD=
- Parkinson disease;
- PDQ-39=
- 39-item Parkinson Disease Questionnaire;
- PGI-I=
- Patient Global Impression–Improvement;
- PPS=
- per-protocol set;
- UPDRS=
- Unified Parkinson's Disease Rating Scale
Footnotes
Study funding: Sponsored by Boehringer Ingelheim.
The Pramipexole ER Studies Group Coinvestigators are listed in appendix e-1 on the Neurology® Web site at www.neurology.org.
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See page 767
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Supplemental data at www.neurology.org
- Received June 2, 2010.
- Accepted May 4, 2011.
- Copyright © 2011 by AAN Enterprises, Inc.
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