A double-blind, placebo-controlled, randomized, multi-center study of pramipexole in advanced Parkinson's disease

Pramipexole (SND 919), a potent non-ergot dopamine agonist, or placebo, was administered to 69 patients with advanced Parkinson's disease (33 received placebo, 36 received pramipexole) in a double-blind, randomized, multi-center study in which individually optimized doses of l -dopa plus a dopa decarboxylase inhibitor were associated with dyskinesia, "on–off" fluctuation, dystonia, akinesia, or end-of-dose deterioration. Study medication was titrated over 7 weeks to the maximal tolerated dose or to the maximal dose allowed by the study (5 mg/day in four divided doses). Dosing was maintained for 4 weeks and then tapered during the final week. Total score on the Unified Parkinson's Disease Rating Scale (UPDRS) for the intent-to-treat population was significantly improved in the pramipexole-treated group compared with the placebo-treated group (16.9 ± 14.9 vs 9.0 ± 16.1; p = 0.0184). By the end of maintenance, the mean reduction in l -dopa requirement was −150.7 mg for pramipexole-treated patients compared to −10.6 for placebo-treated patients. The most common adverse events (> 10%) were dizziness, insomnia, nausea, and postural hypotension. Aggravated parkinsonism occurred only after withdrawal of the study medication. Treatment with pramipexole in doses up to 5 mg/day was safe and well tolerated by patients with advanced Parkinson's disease.