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Efficacy, safety, and tolerability of overnight switching from immediate‐ to once daily extended‐release pramipexole in early Parkinson's disease
Author(s) -
Rascol Olivier,
Barone Paolo,
Hauser Robert A.,
Mizuno Yoshikuni,
Poewe Werner,
Schapira Anthony H.V.,
Salin Laurence,
Sohr Mandy,
Debieuvre Catherine
Publication year - 2010
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.23262
Subject(s) - pramipexole , tolerability , parkinson's disease , medicine , adverse effect , clinical endpoint , clinical global impression , levodopa , confidence interval , extended release , anesthesia , randomized controlled trial , pharmacology , disease , placebo , alternative medicine , pathology
The aim of this article is to test the feasibility, in early Parkinson's disease (PD), of an overnight switch from immediate‐release (IR) pramipexole to a new once‐daily extended‐release (ER) formulation. Nonfluctuating patients on pramipexole IR three‐times daily, alone or with levodopa, for early PD were randomly switched overnight to double‐blind IR three‐times daily (N = 52) or ER once‐daily (N = 104) at initially unchanged daily dosage. Successful switching (defined as no worsening >15% of baseline UPDRS II+III score and no drug‐related adverse event withdrawal) was assessed at 9 weeks, after optional dosage adjustments (primary endpoint), and at 4 weeks, before adjustment. Other secondary endpoints included adjusted mean changes from baseline in UPDRS scores and proportion of responders based on Clinical or Patient Global Impression (CGI/PGI). Absolute difference between percentage of successful switch to ER versus IR was tested for ER noninferiority, defined as a 95% confidence‐interval lower bound not exceeding −15%. At 9 weeks, 84.5% of the ER group had been successfully switched, versus 94.2% for IR. Noninferiority was not demonstrated, with a difference of −9.76% (95% CI: [−18.81%, +1.66%]). At 4 weeks, 81.6% of the ER group had been successfully switched, versus 92.3% for IR, a difference of −10.75% (95% CI: [−20.51%, +1.48%]). UPDRS changes and CGI/PGI analyses showed no differences between the groups. Both formulations were safe and well tolerated. Pramipexole ER was not equivalent to IR, but the difference was marginal. The fact that >80% of the patients successfully switched overnight at unchanged dosage shows that this practice was feasible in most patients. © 2010 Movement Disorder Society