title: Pharmacokinetics of rotigotine transdermal system in adolescents with idiopathic restless legs syndrome (Willis-Ekbom disease).
abstract: OBJECTIVE
  To investigate the pharmacokinetics (PK) of rotigotine transdermal system in adolescents with moderate-to-severe idiopathic restless legs syndrome (RLS).
  
  
  METHODS
  This multicenter, open-label, dose-escalation study enrolled patients ≥13 to <18 years of age. Rotigotine transdermal patches were applied daily and up-titrated weekly: 0.5, 1, 2, 3 mg/24 h. Blood samples were collected on the final day of each dose step. Primary PK variables were the apparent total body clearance (CL/f; L/h) and volume of distribution at steady state (VSS/f; L) of unconjugated rotigotine for each dose step, calculated for the PK per-protocol set (PKPPS). Other PK, safety, and efficacy variables (International RLS Study Group Rating Scale [IRLS]; Clinical Global Impressions Item 1 [CGI-1]) were assessed.
  
  
  RESULTS
  Of 24 patients who received rotigotine, 23 completed all dose steps and 17 formed the PKPPS. Least-squares mean (95% confidence interval) CL/f and VSS/f values were broadly similar across all dose steps (CL/f: 0.5 mg/24 h: 676.86 [408.50-1121.51]; 1 mg/24 h: 671.72 [459.11-982.80]; 2 mg/24 h: 937.56 [658.50-1334.89]; 3 mg/24 h: 1088.77 [723.47-1638.53]; VSS/f: 5403.16 [2850.67-10,241.17]; 6220.79 [3842.05-10,072.28]; 7114.01 [4547.88-11,128.07]; 6037.92 [3598.36-10,131.41]). Among 23 patients with efficacy data, mean IRLS and CGI-1 scores improved at each dosage level. Adverse events reported by ≥3 patients were nausea (seven) and application site reactions (four).
  
  
  CONCLUSIONS
  Key PK properties of rotigotine in adolescent patients with moderate-to-severe idiopathic RLS were comparable to those previously observed in adults. Rotigotine improved RLS symptoms and was well tolerated. ClinicalTrials.gov: NCT01495793.
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany. Electronic address: Jan-Peer.Elshoff@ucb.com.
authors.forename: Jan-Peer
authors.initials: JP
authors.lastname: Elshoff
authors.affiliation: FutureSearch Trials of Neurology and Sleep Lab, Austin, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hudson
authors.affiliation: University of Illinois School of Medicine at Urbana-Champaign and Carle Foundation Hospital, Urbana, IL, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Picchietti
authors.affiliation: Josephson Wallack Munshower Neurology, Indianapolis, IN, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Ridel
authors.affiliation: Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Walters
authors.affiliation: UCB Pharma, Raleigh, NC, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Doggett
authors.affiliation: UCB Pharma, Smyrna, GA, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Moran
authors.affiliation: UCB Pharma, Raleigh, NC, USA.
authors.forename: Marga
authors.initials: M
authors.lastname: Oortgiesen
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ramirez
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Schollmayer
mesh_terms: D000293:Adolescent; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D012148:Restless Legs Syndrome / Q000188:drug therapy*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D057968:Transdermal Patch
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine
keywords: Adolescent; Dopamine agonist; Periodic limb movements in sleep; Restless legs syndrome; Sleep disorder; Willis–Ekbom disease