title: Efficacy, safety, and tolerability of overnight switching from immediate- to once daily extended-release pramipexole in early Parkinson's disease.
abstract: 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.
authors.affiliation: Departments of Clinical Pharmacology and Neurosciences, Toulouse University Hospital, INSERM CIC9302-UMR825 Toulouse, France. rascol@cict.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Anthony H V
authors.initials: AH
authors.lastname: Schapira
authors.forename: Laurence
authors.initials: L
authors.lastname: Salin
authors.forename: Mandy
authors.initials: M
authors.lastname: Sohr
authors.forename: Catherine
authors.initials: C
authors.lastname: Debieuvre
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000009:adverse effects*; D016001:Confidence Intervals; D003692:Delayed-Action Preparations / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D000077487:Pramipexole; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D003692:Delayed-Action Preparations; D000077487:Pramipexole