Extended-release pramipexole in advanced Parkinson disease: a randomized controlled trial.

BACKGROUND: In advanced Parkinson disease (PD), immediate-release pramipexole, taken 3 times daily, improves symptoms and quality of life. A once-daily extended-release formulation may be an effective and simple alternative therapy.

METHODS: For a multicenter randomized, double-blind, parallel trial of extended- and immediate-release pramipexole vs placebo, patients experiencing motor fluctuations while taking levodopa underwent flexible study drug titration and then maintenance at optimized dosage (0.375-4.5 mg/day). The primary endpoint was a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 18 weeks, with further assessments at 33 weeks in a subset of patients. Adverse events were recorded throughout.

RESULTS: Among 507 patients in the 18-week analyses, UPDRS II+III scores decreased (from baseline means of 40.0-41.7) by an adjusted mean of -11.0 for extended-release pramipexole and -12.8 for immediate-release pramipexole vs -6.1 for placebo (p = 0.0001 and p < 0.0001) and off-time decreased (from baseline means of 5.8-6.0 hours/day) by an adjusted mean of -2.1 and -2.5 vs -1.4 hours/day (p = 0.0199 and p < 0.0001). Other outcomes were largely corroborative, including a significant improvement in early morning off symptoms. Among 249 pramipexole patients completing 33 weeks, UPDRS II+III and off-time findings showed ≤10.1% change from 18-week values. Both formulations were well-tolerated.

CONCLUSIONS: Extended-release pramipexole significantly improved UPDRS score and off-time compared with placebo, with similar efficacy, tolerability, and safety of immediate-release pramipexole compared with placebo.

CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the extended-release form of pramipexole, taken once daily, is efficacious as an adjunct to levodopa in advanced PD.