Pharmacokinetics of rotigotine transdermal system in adolescents with idiopathic restless legs syndrome (Willis–Ekbom disease)

Jan Peer Elshoff, John Hudson, Daniel L Picchietti, Keith Ridel, Arthur S. Walters, Kimberly Doggett, Kimberly Moran, Marga Oortgiesen, Francisco Ramirez, Erwin Schollmayer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)48-55
Number of pages8
JournalSleep Medicine
Volume32
DOIs
StatePublished - Apr 1 2017

Keywords

  • Adolescent
  • Dopamine agonist
  • Periodic limb movements in sleep
  • Restless legs syndrome
  • Sleep disorder
  • Willis–Ekbom disease

ASJC Scopus subject areas

  • Medicine(all)

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