The long-term safety and efficacy of pramipexole in advanced Parkinson's disease

Objective: To assess the long-term safety and efficacy of pramipexole in ad vanced Parkinson's disease over a four year time period. Methods: This study is an open-label extension trial of pramipexole for Par kinson's disease open to patients completing a double-blind placebo control led safety and efficacy trial of this drug. Three hundred and six patients entered the trial. These patients had moderate to severe PD (stage II-IV Ho ehn and Yahr during off time) and were experiencing motor fluctuations. Pat ients were titrated over a six week period and then entered a maintenance p hase which lasted lip to 50 months. Patients were evaluated every 3 months using thr Unified Parkinson's Disease Rating Scale (UPDRS II, III and IV) a nd modified Schwab and England scale (S/E). Results: Sixty-four percent (197) of the 306 patients who entered this stud y completed it. Patients showed steady improvement over the 6 week ascendin g dose interval when pramipexole was reintroduced into the trial as the ope n-label study medication. Over the duration of the trial patients slowly re turned to their baseline levels, This was true for all measures evaluated e xcept for the UPDRS part IV. On UPDRS part IV patients remained below their baseline score which indicated an improvement for the duration of the stud y. Patterns similar to the overall scores were seen when the individual com ponents of the UPDRS scale part II for "on" and "off" periods and part III were evaluated. However tremor during "on" periods showed improvement over baseline for the duration of the trial. The most common adverse events seco ndary to pramipexole occurring in greater than 10% of patients included dys kinesias, asymptomatic orthostatic hypotension, dizziness, insomnia, and ha llucinations, Conclusion: Pramipexole was well tolerated for up to 4 years. Pramipexole t reatment appeared to show continued efficacy in the treatment of Parkinson' s disease for 3 years in this open-label descriptive study. After 3 years t here was a gradual return to baseline motor states perhaps suggesting progr ession of Parkinson's disease. (C) 2001 Elsevier Science Ltd. All rights re served.