DOUBLE-BLIND COMPARISON OF PRAMIPEXOLE AND BROMOCRIPTINE TREATMENT WITH PLACEBO IN ADVANCED PARKINSONS-DISEASE

Pramipexole is a new, selective, nonergoline dopamine agonist that act s on D-2 and preferentially on D-3 dopamine receptors. Phase II and II I clinical trials have shown this drug to be useful in treating both e arly and advanced Parkinson's disease (PD) patients. A double-blind, r andomized, multicenter study was performed to compare the safety, tole rance, and efficacy of pramipexole versus placebo in patients with adv anced PD with motor fluctuations. A bromocriptine treatment group was included to enable comparisons between bromocriptine and placebo group s, but the study was not powered to show statistical differences betwe en the active treatment groups. The study included 247 patients with ' 'wearing off.'' Patients were Hoehn and Yahr stages II to IV during '' on'' times. The trial included three phases: dose escalation, 6 months ' maintenance, and dose reduction. The primary end points were the Uni fied Parkinson's Disease Rating Scale (UPDRS) parts II and III. Up to 4.5 mg per day of pramipexole and 30 mg per day bf bromocriptine were used. The results of the study showed that the UPDRS part II improved by 26.7% for pramipexole (p = 0.0002) and 14% for bromocriptine (p = 0 .02) versus 4.8% for placebo. The UPDRS part III showed improvements o f 34% for pramipexole (p = 0.0006) and 23.8% for bromocriptine (p = 0. 01) versus 5.7% for placebo. There were no major differences in safety data. In the active treatment groups there were more reports of dyski nesia and nausea compared with placebo. In regard to comparison of the Global Clinical Assessment of Efficacy between active treatment group s, there was a trend to significance (p = 0.056) in favor of pramipexo le. We conclude that pramipexole-treated patients with advanced PD imp roved significantly more than placebo for both primary end points.