title: A randomized study of rotigotine dose response on 'off' time in advanced Parkinson's disease.
abstract: BACKGROUND
  Previous phase III studies in patients with advanced Parkinson's disease (PD) not adequately controlled on levodopa demonstrated significant reduction of 'off' time with rotigotine transdermal system up to 16 mg/24 h. However, the minimal effective dose has not been established.
  
  
  OBJECTIVE
  This international, randomized, double-blind, placebo-controlled study (SP921; NCT00522379) investigated rotigotine dose response up to 8 mg/24 h.
  
  
  METHODS
  Patients with advanced idiopathic PD (≥2.5 h of daily 'off' time on stable doses of levodopa) were randomized 1:1:1:1:1 to receive rotigotine 2, 4, 6, or 8 mg/24 h or placebo, titrated over 4 weeks and maintained for 12 weeks. The primary efficacy variable was change from baseline to end of maintenance in absolute time spent 'off'.
  
  
  RESULTS
  409/514 (80%) randomized patients completed maintenance. Mean (±SD) baseline daily 'off' times (h/day) were placebo: 6.4 (±2.5), rotigotine 2-8 mg/24 h: 6.4 (±2.6). Rotigotine 8 mg/24 h was the minimal dose to significantly reduce 'off' time versus placebo. LS mean (±SE) absolute change in daily 'off' time (h/day) from baseline was -2.4 (±0.28) with rotigotine 8 mg/24 h, and -1.5 (±0.26) with placebo; absolute change in 'off' time in the 8 mg/24 h group compared with placebo was -0.85 h/day (95% CI -1.59, -0.11; p = 0.024). There was an apparent dose-dependent trend. Adverse events (AEs) reported at a higher incidence in the rotigotine 8 mg/24 h group versus placebo included application site reactions, nausea, dry mouth, and dyskinesia; there was no worsening of insomnia, somnolence, orthostatic hypotension, confusional state or hallucinations, even in patients ≥75 years of age.
  
  
  CONCLUSIONS
  The minimal statistically significant effective dose of rotigotine to reduce absolute 'off' time was 8 mg/24 h. The AE profile was similar to previous studies.
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Nicholas
authors.affiliation: Department of Neurology, Nizam's Institute of Medical Sciences, Andhra Pradesh, India.
authors.forename: Rupam
authors.initials: R
authors.lastname: Borgohain
authors.affiliation: Department of Neurology, Universidad de Santiago de Chile, Santiago, Chile.
authors.forename: Pedro
authors.initials: P
authors.lastname: Chaná
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Surmann
authors.affiliation: Evidence Scientific Solutions Ltd, London, UK.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Thompson
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Bauer
authors.affiliation: UCB Pharma, Raleigh, NC, USA.
authors.forename: John
authors.initials: J
authors.lastname: Whitesides
authors.affiliation: Department of Neurology, University of Toledo, Toledo, OH, USA.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Elmer
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage*; D013876:Thiophenes / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine
keywords: Parkinson's disease; dopamine receptor agonist; dose-response relationship; randomized controlled trial; rotigotine