The safety and tolerability of rotigotine transdermal system over a 6-year period in patients with early-stage Parkinson's disease

J Neural Transm (Vienna). 2013 Sep;120(9):1321-9. doi: 10.1007/s00702-013-1001-5. Epub 2013 Mar 19.

Abstract

This open-label extension (SP716; NCT00599196) of a 6-month, double-blind, randomized study (SP513) investigated the safety and tolerability of rotigotine transdermal system over up to ~6 years in patients with Parkinson's disease (PD; early-stage PD at double-blind enrollment). Eligible patients completing the 6-month study received optimal dose open-label rotigotine (≤ 16 mg/24 h) for up to ~6 years. Adjunctive levodopa was permitted. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Analysis of adjunctive levodopa use, dyskinesias [unified Parkinson's disease rating scale (UPDRS) IV], and efficacy (UPDRS II + III total score) were also assessed. Of 381 patients enrolled in the open-label extension, 52 % were still in the study at time of closure; 24 % withdrew because of AEs and 6 % because of lack of efficacy. Patients received rotigotine for a median duration of 1,564.5 days (~4 years, 3 months; range 5-2, 145 days). 69 % of patients started supplemental levodopa; median time to levodopa was 485 days (~1 year, 4 months). Most common AEs (% per patient-year) were somnolence (18 %), application site reactions (12 %), nausea (9 %), peripheral edema (7 %), and fall (7 %). AEs indicative of impulsive-compulsive behavior were recorded in 25 (7 %) patients. Dyskinesias were experienced by 65 (17 %) patients; the majority [47 of 65 (72 %)] reported first dyskinesia after starting levodopa. Mean UPDRS II + III total scores remained below double-blind baseline for 4 years (assessment of all patients). In conclusion, rotigotine was generally well tolerated for up to ~6 years in patients with early-stage PD. The AEs reported were in line with previous studies of rotigotine transdermal system, with typical dopaminergic side effects and application site reactions seen.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aged
  • Aged, 80 and over
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / adverse effects*
  • Antiparkinson Agents / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Dyskinesia, Drug-Induced / epidemiology
  • Electrocardiography / drug effects
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Levodopa / therapeutic use
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*
  • Prospective Studies
  • Survival Analysis
  • Tetrahydronaphthalenes / administration & dosage
  • Tetrahydronaphthalenes / adverse effects*
  • Tetrahydronaphthalenes / therapeutic use
  • Thiophenes / administration & dosage
  • Thiophenes / adverse effects*
  • Thiophenes / therapeutic use
  • Transdermal Patch
  • Treatment Outcome

Substances

  • Antiparkinson Agents
  • Tetrahydronaphthalenes
  • Thiophenes
  • Levodopa
  • rotigotine

Associated data

  • ClinicalTrials.gov/NCT00599196