title: Extended-release pramipexole in advanced Parkinson disease: a randomized controlled trial.
abstract: BACKGROUND
  In advanced Parkinson disease (PD), immediate-release pramipexole, taken 3 times daily, improves symptoms and quality of life. A once-daily extended-release formulation may be an effective and simple alternative therapy.
  
  
  METHODS
  For a multicenter randomized, double-blind, parallel trial of extended- and immediate-release pramipexole vs placebo, patients experiencing motor fluctuations while taking levodopa underwent flexible study drug titration and then maintenance at optimized dosage (0.375-4.5 mg/day). The primary endpoint was a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 18 weeks, with further assessments at 33 weeks in a subset of patients. Adverse events were recorded throughout.
  
  
  RESULTS
  Among 507 patients in the 18-week analyses, UPDRS II+III scores decreased (from baseline means of 40.0-41.7) by an adjusted mean of -11.0 for extended-release pramipexole and -12.8 for immediate-release pramipexole vs -6.1 for placebo (p = 0.0001 and p < 0.0001) and off-time decreased (from baseline means of 5.8-6.0 hours/day) by an adjusted mean of -2.1 and -2.5 vs -1.4 hours/day (p = 0.0199 and p < 0.0001). Other outcomes were largely corroborative, including a significant improvement in early morning off symptoms. Among 249 pramipexole patients completing 33 weeks, UPDRS II+III and off-time findings showed ≤10.1% change from 18-week values. Both formulations were well-tolerated.
  
  
  CONCLUSIONS
  Extended-release pramipexole significantly improved UPDRS score and off-time compared with placebo, with similar efficacy, tolerability, and safety of immediate-release pramipexole compared with placebo.
  
  
  METHODS
  This study provides Class I evidence that the extended-release form of pramipexole, taken once daily, is efficacious as an adjunct to levodopa in advanced PD.
authors.affiliation: Institute of Neurology, University College London, London, UK. a.schapira@ucl.ac.uk
authors.forename: Anthony H V
authors.initials: AH
authors.lastname: Schapira
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: O
authors.initials: O
authors.lastname: Rascol
authors.forename: M
authors.initials: M
authors.lastname: Busse
authors.forename: L
authors.initials: L
authors.lastname: Salin
authors.forename: N
authors.initials: N
authors.lastname: Juhel
authors.forename: W
authors.initials: W
authors.lastname: Poewe
mesh_terms: D000328:Adult; D000368:Aged; 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; D008609:Mental Status Schedule; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D000077487:Pramipexole; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D000077487:Pramipexole