title: Randomized, double-blind, multicenter evaluation of pramipexole extended release once daily in early Parkinson's disease.
abstract: The objective of this study was to evaluate the efficacy and safety of pramipexole extended release (ER) administered once daily in early Parkinson's disease (PD). Pramipexole immediate release (IR) administered three times daily (TID) is an efficacious and generally well-tolerated treatment for PD. A pramipexole ER formulation is now available. We performed a randomized, double-blind, placebo and active comparator-controlled trial in subjects with early PD. The primary efficacy and safety evaluation of pramipexole ER compared with placebo took place at week 18. Two hundred fifty-nine subjects were randomized 2:2:1 to treatment with pramipexole ER once daily, pramipexole IR TID, or placebo. Levodopa rescue was required by 7 subjects in the placebo group (14%), 3 subjects in the pramipexole ER group (2.9%, P = 0.0160), and 1 subject in the pramipexole IR group (1.0%, P = 0.0017). Adjusted mean [standard error (SE)] change in Unified Parkinson Disease Rating Scale (UPDRS) II [activities of daily living (ADL)] + III (motor) scores from baseline to week 18, including post-levodopa rescue evaluations, was -5.1 (1.3) in the placebo group, -8.1 (1.1) in the pramipexole ER group (P = 0.0282), and -8.4 (1.1) in the pramipexole IR group (P = 0.0153). Adjusted mean (SE) change in UPDRS ADL + motor scores, censoring post-levodopa rescue data, was -2.7 (1.3) in the placebo group, -7.4 (1.1) in the pramipexole ER group (P = 0.0010), and -7.5 (1.1) in the pramipexole IR group (P = 0.0006). Adverse events more common with pramipexole ER than placebo included somnolence, nausea, constipation, and fatigue. Pramipexole ER administered once daily was demonstrated to be efficacious compared with placebo and provided similar efficacy and tolerability as pramipexole IR administered TID.
authors.affiliation: Department of Neurology, University of South Florida, Tampa, Florida 33606, USA. rhauser@health.usf.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.forename: Anthony H V
authors.initials: AH
authors.lastname: Schapira
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Laurence
authors.initials: L
authors.lastname: Salin
authors.forename: Monika
authors.initials: M
authors.lastname: Haaksma
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Juhel
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D017060:Patient Satisfaction; D000077487:Pramipexole; D011788:Quality of Life; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D003692:Delayed-Action Preparations; D007980:Levodopa; D000077487:Pramipexole