title: Effects of rotigotine on daytime symptoms in patients with primary restless legs syndrome: a randomized, placebo-controlled study.
abstract: OBJECTIVE
  This 12 week double-blind, placebo-controlled study (ClinicalTrials.gov: NCT01569464) was conducted to evaluate the effects of rotigotine transdermal patch on daytime symptoms in patients with idiopathic restless legs syndrome (RLS).
  
  
  METHODS
  Adult patients with moderate-to-severe RLS were randomized to rotigotine (optimal dose: 1-3 mg/24 h) or placebo. A modified four-assessment version (4:00 pm, 6:00 pm, 8:00 pm, and 10:00 pm) of the Multiple Suggested Immobilization Test (m-SIT) was performed at baseline and end of 4 week maintenance (EoM). Primary study outcomes were change from baseline to EoM in International Restless Legs Syndrome Rating Scale (IRLS) and in average of means for the m-SIT Discomfort Scale (m-SIT-DS) (combined average of mean values from each of the individual assessments). Secondary outcomes included average of means of Periodic Limb Movement during Wakefulness Index (PLMWI; PLM/hour) for the combination of m-SIT.
  
  
  RESULTS
  A total of 150 patients were randomized and 137 (rotigotine: 92/101 [91.1%]; placebo: 45/49 [91.8%]) completed maintenance. All 150 randomized patients were assessed for efficacy. At EoM, mean change in IRLS was -14.9 ± 9.3 with rotigotine vs. -12.7 ± 7.6 with placebo (ANCOVA, LS mean treatment difference [95% CI]: -0.27 [-2.96, 2.42]; p = 0.8451). Changes in average of means of m-SIT-DS values of each individual SIT were comparable with rotigotine (-2.68 ± 2.31) vs. placebo (-2.62 ± 2.61) (ANCOVA, LS mean treatment difference [95% CI]: 0.07 [-0.61, 0.75]; p = 0.8336) and comparable reductions in PLMWI were observed in both treatment groups (8.34 [-8.50, 25.17]; p = 0.3290). Rotigotine was generally well tolerated. Application site reactions (rotigotine: 20 patients [19.8%]; placebo: 4 [8.2%]) and nausea (16 [15.8%]; 3 [6.1%]) were the most common AEs.
  
  
  CONCLUSIONS
  Rotigotine was beneficial in improving overall RLS symptom severity (assessed by IRLS) and RLS symptom severity at various times of the day (m-SIT-DS); however, superiority to placebo was not established.
authors.affiliation: a a Sleep Research Institute , Madrid , Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Garcia-Borreguero
authors.affiliation: b b Department of Neurology , Johns Hopkins Bayview Medical Center , Baltimore , MD , USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Allen
authors.affiliation: c c FutureSearch Trials of Neurology , Austin , TX , USA.
authors.forename: John
authors.initials: J
authors.lastname: Hudson
authors.affiliation: d d UCB Pharma , Brussels , Belgium.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Dohin
authors.affiliation: e e UCB Pharma , Monheim am Rhein , Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Grieger
authors.affiliation: f f UCB Pharma , Smyrna , GA , USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Moran
authors.affiliation: e e UCB Pharma , Monheim am Rhein , Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Schollmayer
authors.affiliation: g g UCB Pharma , Raleigh , NC , USA.
authors.forename: René
authors.initials: R
authors.lastname: Smit
authors.affiliation: h h Massachusetts General Hospital , Boston , MA , USA.
authors.forename: John
authors.initials: J
authors.lastname: Winkelman
mesh_terms: D000328:Adult; D000368:Aged; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012148:Restless Legs Syndrome / Q000188:drug therapy*; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine
keywords: Dopamine receptor agonist; Periodic limb movements; Restless legs syndrome; Rotigotine