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Extended-Release Pramipexole in Early and Advanced Parkinson's Disease
Abstract & Commentary
By Melissa J. Nirenberg, MD, PhD, Assistant Professor, Neurology and Neuroscience, Weill Cornell Medical College. Dr. Nirenberg reports no financial relationships relevant to this field of study.
Synopsis: Extended-release pramipexole is effective in both early and advanced Parkinson's disease, with a safety and tolerability profile similar to that of immediate-release pramipexole.
Sources: Poewe W, et al. Extended-release pramipexole in early Parkinson disease: A 33-week randomized controlled trial. Neurology 2011;77:759-766. Schapira AH, et al. Extended-release pramipexole in advanced Parkinson disease: A randomized controlled trial. Neurology 2011;77:767-774.
Dopamine agonist medications, such as pramipexole (Mirapex) and ropinirole (Requip), are highly effective in the treatment of both early and more advanced stages of Parkinson's disease (PD). They often are favored in the treatment of early PD, because they are less likely to produce dyskinesias than levodopa. In addition, they can be useful as adjunctive therapy to reduce end-of-dose wearing off in patients with advanced PD. Based on their half lives, the immediate-release forms of pramipexole (pramipexole IR) and ropinirole are usually dosed three times daily.
In these two consecutive papers, the authors evaluate the safety and efficacy of a once-daily, extended-release preparation of pramipexole (pramipexole ER; marketed in this country as Mirapex ER®), in early PD and advanced PD, respectively. Both were multicenter, randomized, double-blind parallel studies that compared pramipexole ER, pramipexole IR, and placebo. The studies were funded by Boehringer Ingelheim.
The first study enrolled subjects with early PD who were not currently on dopamine agonist or levodopa therapy. Subjects were either treated with placebo (n = 103), pramipexole ER (n = 223), or pramipexole IR (n = 213). The study drug was titrated over 7 weeks, followed by 26 weeks of maintenance therapy. Levodopa was permitted as a rescue medication. The primary outcome measure was the change in the sum of Unified Parkinson's Disease Rating Scale (UPDRS) part II (activities of daily living) + part III (motor) scores at the 33-week time point. The authors show that pramipexole IR and pramipexole ER were both superior to placebo in this regard. In addition, using predefined criteria, they demonstrated non-inferiority of pramipexole ER vs pramipexole IR.
The second study enrolled subjects with advanced PD and associated motor fluctuations. Subjects were randomized to receive placebo (n = 178), pramipexole ER (n = 165), or pramipexole IR (n = 175). The study drug was titrated over 7 weeks to an optimized dosage for each subject, followed by maintenance therapy at that dosage. The primary outcome measure was the change in the sum of UPDRS II + III scores at the 18-week time point. As in the prior study, the authors showed that UPDRS II + III scores decreased in both the pramipexole ER and pramipexole IR groups as compared with placebo. In addition, off-time decreased in both the pramipexole ER and the pramipexole IR groups vs placebo.
In both studies, the safety and efficacy of ER and IR preparations were comparable, with common side effects including somnolence, gastrointestinal symptoms, and dizziness. New-onset impulse control disorders were also reported in both studies, mainly in the two active treatment groups.
In these studies, the authors establish that pramipexole ER is an effective treatment for early and advanced PD, with a side effect profile similar to that of pramipexole IR and other dopamine agonists. The studies were both well-designed, appropriately powered, and met their primary endpoints. The once-daily dosing of pramipexole ER offers the obvious advantages of convenience and the potential for increased medication adherence. It is not known, however, whether pramipexole ER may offer any additional benefits when compared with pramipexole IR. For now, physicians need to weigh whether the benefits of once-daily dosing justify the additional cost of pramipexole ER.