title: The safety and tolerability of rotigotine transdermal system over a 6-year period in patients with early-stage Parkinson's disease.
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.
authors.affiliation: Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, 6 Weizmann Street, 64239, Tel-Aviv, Israel. nirg@tlvmc.gov.il
authors.forename: Nir
authors.initials: N
authors.lastname: Giladi
authors.forename: Babak
authors.initials: B
authors.lastname: Boroojerdi
authors.forename: Erwin
authors.initials: E
authors.lastname: Surmann
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D011446:Prospective Studies; D016019:Survival Analysis; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D057968:Transdermal Patch; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D007980:Levodopa; C047508:rotigotine