Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study

Objectives-Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was in vestigated as an add on drug in advanced parkinsonian patients with motor f luctuations to assess efficacy, safety, and tolerance. Methods-Seventy eight patients of either sex with advanced Parkinson's dise ase and treatment complications such as motor fluctuations were enrolled in to a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with pramipexole (n=34) versus placeb o (n=44) to a previously stabilised antiparkinsonian medication (7 week dos e titration interval, 4 week maintenance period). The primary end point of efficacy was the change from baseline in the total score of the unified Par kinson's disease rating scale (UPDRS) in the on "period" (2 hours after int ake of study medication). Safety and tolerability were assessed on the basi s of adverse events, vital signs, laboratory measurements, and ECG recordin gs. Results-There was a significant improvement of the pramipexole group in UPD RS total scores, subscores part II, III (activities of daily living and mot or examination), and IV (complications of therapy). Mean UPDRS total score decreased by 37.3% under pramipexole compared with 12.2% under placebo (p<0 .001). Patients under pramipexole reported an overall reduction in "off" pe riods of 12%- resulting in 1.7 more hours "on" time a day-compared with an increase in "off" periods of 2% under placebo. There were no unexpected saf ety results. The adverse event profile disclosed a high tolerability. The m ost important adverse events under pramipexole were fatigue, dyskinesia, an d vivid dreams. Conclusion-Pramipexole administration is an efficacious and well tolerated add on therapy in patients with advanced Parkinson's disease with an improv ement in activities of daily living, motor function, and treatment associat ed complications.