title: Effects of rotigotine transdermal patch in patients with Parkinson's disease presenting with non-motor symptoms - results of a double-blind, randomized, placebo-controlled trial.
abstract: OBJECTIVE
  Non-motor symptoms (NMS) of Parkinson's disease (PD) have a major impact on health-related quality of life. This is the first randomized controlled trial to use the NMS Scale (NMSS) as a primary outcome to assess treatment effects on NMS in PD.
  
  
  METHODS
  In this double-blind trial (NCT01300819), patients with PD and a total NMSS score ≥40 were randomized (2:1) to rotigotine or placebo, titrated over 1-7 weeks to optimal dose (≤8 mg/24 h for patients not receiving levodopa, ≤16 mg/24 h for patients receiving levodopa), maintained for 12 weeks. The primary outcome was change in NMSS total score from baseline to end of maintenance. Secondary outcomes were the nine NMSS domains, Unified Parkinson's Disease Rating Scale (UPDRS) III (motor) and the 39-item Parkinson's Disease Questionnaire (PDQ-39).
  
  
  RESULTS
  In total, 283/349 (81.1%) randomized patients completed the trial; 211 rotigotine and 122 placebo were included in the full analysis set. The NMSS total score decreased by 23 (rotigotine) and 19 (placebo) points; the treatment difference was not statistically significant (-3.58; 95% confidence interval -8.43, 1.26; P = 0.147). Numerically greater than placebo improvements were detected in the 'mood/apathy' and 'miscellaneous' NMSS domains (P < 0.05). Treatment differences in UPDRS III (-2.60; -4.27, -0.92; P = 0.002) and PDQ-39 (-2.79; -5.21, -0.37; P = 0.024) favoured rotigotine. Adverse events reported more frequently with rotigotine were nausea, application site reactions, somnolence and headache.
  
  
  CONCLUSIONS
  Rotigotine improvement in the multi-domain NMSS total score was not superior to placebo. A different sensitivity of individual NMSS domains to dopaminergic therapy and a large placebo effect may have contributed to these findings.
authors.affiliation: Parkinson and Movement Disorders Unit, IRCCS Hospital San Camillo, Venice, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Antonini
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Bauer
authors.affiliation: UCB Pharma, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Dohin
authors.affiliation: Department of Neurology, Philipps University, Marburg, Germany.
authors.forename: W H
authors.initials: WH
authors.lastname: Oertel
authors.affiliation: Clinical Investigation Centre CIC1436, and Departments of Clinical Pharmacology and Neurosciences, INSERM and Toulouse University Hospital, Toulouse, France.
authors.forename: O
authors.initials: O
authors.lastname: Rascol
authors.affiliation: Department of Neurology, University of Dresden, Dresden, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Reichmann
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmid
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.affiliation: Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, IDIBAPS, Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona Catalonia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Tolosa
authors.affiliation: National Parkinson Foundation International Centre of Excellence, King's College Hospital, Kings College and Kings Health Partners, London, UK.
authors.forename: K Ray
authors.initials: KR
authors.lastname: Chaudhuri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057565:Apathy / Q000187:drug effects; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy*; D011788:Quality of Life; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D057968:Transdermal Patch
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine
keywords: Parkinson's disease; non-motor symptoms; non-motor symptoms scale; randomized controlled trial