title: Efficacy of rotigotine transdermal system in severe restless legs syndrome: a randomized, double-blind, placebo-controlled, six-week dose-finding trial in Europe.
abstract: BACKGROUND
  In a pilot placebo-controlled study, low dosages of 0.5-2mg/24h rotigotine showed a dose-dependent beneficial effect in restless legs syndrome (RLS) patients.
  
  
  METHODS
  Efficacy and safety of the dopamine agonist rotigotine, formulated as a once-daily transdermal system (patch), was investigated for five fixed dosages and compared to placebo in patients with idiopathic RLS in a double-blind, randomized, parallel-group, multicenter, six-week dose-finding trial. Primary efficacy measure was the total score of the International RLS Severity Scale (IRLS); in addition, the RLS-6 scales and the Clinical Global Impressions (CGI) were administered.
  
  
  RESULTS
  Of 371 enrolled patients, 341 patients (mean age 58+/-10years, 67% females) were randomized. The IRLS total score improved between baseline and end of the six-week treatment period by -10.6 (0.5mg/24h rotigotine; patch area 2.5cm2), -15.1 (1mg/24h; 5cm2), -15.7 (2mg/24h; 10cm2), -17.5 (3mg/24h; 15cm2), and -14.8 (4mg/24h, 20cm2) as compared to placebo (-9.2). The hierarchical statistical test procedure demonstrated superiority of rotigotine over placebo for 4mg/24h, 3mg/24h, 2mg/24h, and 1mg/24h, with p-values of 0.0013, <0.0001, 0.0003, and 0.0004, respectively. Only the 0.5mg/24h dose was not different compared to placebo (p=0.2338). The CGI and the RLS-6 severity items supported the efficacy of the rotigotine doses beyond 0.5mg/24h. The most frequent side effects were application site reactions and nausea and tended to be more frequent with higher doses.
  
  
  CONCLUSIONS
  This dose-finding trial identified the range for a maintenance dose of rotigotine from 1mg/24h to 3mg/24h. The lowest dose was ineffective and, with the highest dose, no additional benefit was observed.
authors.affiliation: Department of Neurology, Philipps University, Rudolf-Bultmann-Strasse 8, D-35039 Marburg, Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Heike
authors.initials: H
authors.lastname: Benes
authors.forename: Diego
authors.initials: D
authors.lastname: Garcia-Borreguero
authors.forename: Peter
authors.initials: P
authors.lastname: Geisler
authors.forename: Birgit
authors.initials: B
authors.lastname: Högl
authors.forename: Bernd
authors.initials: B
authors.lastname: Saletu
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Sommerville
authors.forename: Erwin
authors.initials: E
authors.lastname: Schollmayer
authors.forename: Ralf
authors.initials: R
authors.lastname: Kohnen
authors.forename: Karin
authors.initials: K
authors.lastname: Stiasny-Kolster
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012148:Restless Legs Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine