title: Extended-release pramipexole in early Parkinson disease: a 33-week randomized controlled trial.
abstract: OBJECTIVE
  To assess the clinical efficacy of a novel once-daily extended-release (ER) formulation of the dopamine agonist pramipexole as monotherapy in patients with early Parkinson disease (PD) and establish its noninferiority vs standard immediate-release (IR) pramipexole.
  
  
  METHODS
  This was a multicenter, double-blind, parallel study of patients with early PD not receiving levodopa or dopamine agonists, randomly assigned to pramipexole IR, pramipexole ER, or placebo. Seven-week flexible titration was followed by 26-week maintenance, with levodopa permitted as rescue medication. The primary analysis was to test pramipexole ER noninferiority to pramipexole IR based on a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 33 weeks, with noninferiority predefined as a treatment group difference for which the lower bound of the 95% confidence interval (CI) did not exceed -3 points.
  
  
  RESULTS
  Among 213 ER and 207 IR recipients, the adjusted mean 33-week UPDRS II+III change (excluding levodopa rescue effects) was -8.2 for ER and -8.7 for IR, a difference of -0.5 with a 95% CI of -2.3 to 1.3. Compared with placebo (n = 103), pramipexole ER and pramipexole IR were significantly superior on UPDRS II+III score, all key secondary outcomes, and almost all other endpoints. On the 39-item Parkinson Disease Questionnaire, superiority of pramipexole ER failed to reach statistical significance. Both formulations were equally safe and well-tolerated.
  
  
  CONCLUSIONS
  As monotherapy for early PD, pramipexole ER was noninferior to pramipexole IR and significantly more effective than placebo. Tolerability and safety did not differ between the formulations.
  
  
  METHODS
  This study provides Class I evidence that pramipexole ER is not inferior to pramipexole IR in patients with early PD.
authors.affiliation: Innsbruck Medical University, Innsbruck, Austria. werner.poewe@i-med.ac.at
authors.forename: W
authors.initials: W
authors.lastname: Poewe
authors.forename: O
authors.initials: O
authors.lastname: Rascol
authors.forename: P
authors.initials: P
authors.lastname: Barone
authors.forename: R A
authors.initials: RA
authors.lastname: Hauser
authors.forename: Y
authors.initials: Y
authors.lastname: Mizuno
authors.forename: M
authors.initials: M
authors.lastname: Haaksma
authors.forename: L
authors.initials: L
authors.lastname: Salin
authors.forename: N
authors.initials: N
authors.lastname: Juhel
authors.forename: A H V
authors.initials: AH
authors.lastname: Schapira
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D000077487:Pramipexole; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D000077487:Pramipexole