Success rate, efficacy, and safety/tolerability of overnight switching from immediate- to extended-release pramipexole in advanced Parkinson's disease
Article first published online: 31 JUL 2012
© 2012 The Author(s) European Journal of Neurology © 2012 EFNS
European Journal of Neurology
Volume 20, Issue 1, pages 180–187, January 2013
How to Cite
Schapira, A. H. V., Barone, P., Hauser, R. A., Mizuno, Y., Rascol, O., Busse, M., Debieuvre, C., Fraessdorf, M. and Poewe, W. (2013), Success rate, efficacy, and safety/tolerability of overnight switching from immediate- to extended-release pramipexole in advanced Parkinson's disease. European Journal of Neurology, 20: 180–187. doi: 10.1111/j.1468-1331.2012.03822.x
- Issue published online: 22 DEC 2012
- Article first published online: 31 JUL 2012
- Manuscript Accepted: 13 JUN 2012
- Manuscript Received: 6 JAN 2012
- Boehringer Ingelheim GmbH
- Parkinson's disease;
Background and purpose
For Parkinson's disease (PD), an extended-release (ER) pramipexole formulation taken once daily, has shown efficacy, safety, and tolerability resembling those of immediate-release (IR) pramipexole taken three times daily. The present study assessed, in advanced PD, the success of an overnight switch from adjunctive IR to ER.
Levodopa users experiencing motor fluctuations were randomized to adjunctive double-blind (DB) placebo, IR, or ER. Amongst completers of ≥18 weeks, ER recipients were kept on DB ER, whilst IR recipients were switched overnight to DB ER at unchanged daily dosage. After a DB week, switch success was assessed. During the next 5 weeks, all patients underwent ER titration to optimal open-label maintenance dosage.
One week post-switch, 86.2% of 123 IR-to-ER and 83.8% of 105 ER-to-ER patients had ≤15% (or ≤3-point, for pre-switch scores ≤20) increase on UPDRS Parts II + III, and 77.9% (of 122) and 70.2% (of 104) had ≤1-h increase in daily OFF-time. At 32 weeks, the groups showed comparable improvements from DB baseline (pramipexole inception), including, on UPDRS II + III, adjusted mean (SE) changes of −14.8 (1.5) for IR-to-ER and −13.3 (1.6) for ER-to-ER. Rates of premature discontinuation owing to adverse events were 6.5% for IR-to-ER and 4.9% for ER-to-ER.
By OFF-time and UPDRS criteria, majorities of patients with advanced PD were successfully switched overnight from pramipexole IR to ER at unchanged daily dosage. During subsequent maintenance, pramipexole showed sustained efficacy, safety, and tolerability, regardless of formulation (IR or ER) in the preceding DB trial.