title: Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson's disease: a double-blind, double-dummy, randomised controlled trial.
abstract: BACKGROUND
  Continuous dopaminergic drug delivery is an unmet medical need in advanced Parkinson's disease. The aim of this trial-Clinical Efficacy of Pramipexole And Transdermal Rotigotine in Advanced PD (CLEOPATRA-PD)-was to assess the efficacy of adjunct treatment with rotigotine in comparison with placebo and with pramipexole in levodopa-treated patients with advanced Parkinson's disease and wearing-off type motor fluctuations.
  
  
  METHODS
  In this randomised controlled trial, eligible participants were randomly assigned to receive either rotigotine (up to 16 mg/24 h as a transdermal patch), pramipexole (up to 4.5 mg/day orally), or placebo for 6 months. Primary efficacy variables were absolute change in total hours "off" (assessed by home diaries) from baseline to end of study and responder rate (defined as the proportion of patients with >or=30% reduction in absolute off time per day). Analyses were done by intention to treat. This trial is registered with the US National Institutes of Health clinical trials database (ClinicalTrials.gov), number NCT00244387.
  
  
  RESULTS
  204 patients were randomly assigned to receive rotigotine, 201 to receive pramipexole, and 101 to receive placebo; 427 (84%) completed the trial. The number of discontinuations in each group was similar; most were for adverse events. The mean dose of rotigotine was 12.95 mg/24 h (SD 3.54), the mean dose of pramipexole was 3.1 mg/day (1.24). Mean absolute change in off time from baseline was -2.5 h (SE 0.20) with rotigotine, -2.8 h (0.20) with pramipexole, and -0.9 h (0.29) with placebo. The absolute change in off time from baseline compared with placebo was -1.58 h (95% CI -2.27 to -0.90; p<0.0001) for rotigotine and -1.94 h (-2.63 to -1.25; p<0.0001) for pramipexole. Responder rates were 67% (134 of 200 patients) for pramipexole, 59.7% (120 of 201 patients) for rotigotine, and 35% (35 of 100 patients) for placebo.
  
  
  CONCLUSIONS
  In terms of change in absolute off time, rotigotine was non-inferior to pramipexole. Continuous delivery of rotigotine as transdermal patches could offer similar efficacy to oral pramipexole in patients with fluctuating Parkinson's disease over 6 months of treatment.
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. werner.poewe@i-med.ac.at
authors.forename: Werner H
authors.initials: WH
authors.lastname: Poewe
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: Niall
authors.initials: N
authors.lastname: Quinn
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Emilia
authors.initials: E
authors.lastname: Martignoni
authors.forename: Markus
authors.initials: M
authors.lastname: Rupp
authors.forename: Babak
authors.initials: B
authors.lastname: Boroojerdi
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D010919:Placebos; D000077487:Pramipexole; D012720:Severity of Illness Index; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage*; D013876:Thiophenes / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D018491:Dopamine Agonists; D010919:Placebos; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D000077487:Pramipexole; C047508:rotigotine