A Randomized Study of Rotigotine Dose Response on ‘Off’ Time in Advanced Parkinson's Disease

• Published in: Journal of Parkinson's disease Vol. 4; no. 3; pp. 361 - 373
• Main Authors: Nicholas, Anthony P., Borgohain, Rupam, Chaná, Pedro, Surmann, Erwin, Thompson, Emily L., Bauer, Lars, Whitesides, John, Elmer, Lawrence W.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 2014
• Subjects: Administration, Cutaneous; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Parkinson Disease - drug therapy; Tetrahydronaphthalenes - administration & dosage; Thiophenes - administration & dosage; Treatment Outcome; rotigotine; Parkinson's disease; dose-response relationship; dopamine receptor agonist; randomized controlled trial
• ISSN: 1877-7171; 1877-718X
• DOI: 10.3233/JPD-130320

Background: Previous phase III studies in patients with advanced Parkinson's disease (PD) not adequately controlled on levodopa demonstrated significant reduction of ‘off’ time with rotigotine transdermal system up to 16 mg/24 h. However, the minimal effective dose has not been established. Objective: This international, randomized, double-blind, placebo-controlled study (SP921; NCT00522379) investigated rotigotine dose response up to 8 mg/24 h. Methods: Patients with advanced idiopathic PD (≥2.5 h of daily ‘off’ time on stable doses of levodopa) were randomized 1:1:1:1:1 to receive rotigotine 2, 4, 6, or 8 mg/24 h or placebo, titrated over 4 weeks and maintained for 12 weeks. The primary efficacy variable was change from baseline to end of maintenance in absolute time spent ‘off’. Results: 409/514 (80%) randomized patients completed maintenance. Mean (±SD) baseline daily ‘off’ times (h/day) were placebo: 6.4 (±2.5), rotigotine 2–8 mg/24 h: 6.4 (±2.6). Rotigotine 8 mg/24 h was the minimal dose to significantly reduce ‘off’ time versus placebo. LS mean (±SE) absolute change in daily ‘off’ time (h/day) from baseline was −2.4 (±0.28) with rotigotine 8 mg/24 h, and −1.5 (±0.26) with placebo; absolute change in ‘off’ time in the 8 mg/24 h group compared with placebo was −0.85 h/day (95% CI −1.59, −0.11; p = 0.024). There was an apparent dose-dependent trend. Adverse events (AEs) reported at a higher incidence in the rotigotine 8 mg/24 h group versus placebo included application site reactions, nausea, dry mouth, and dyskinesia; there was no worsening of insomnia, somnolence, orthostatic hypotension, confusional state or hallucinations, even in patients ≥75 years of age. Conclusions: The minimal statistically significant effective dose of rotigotine to reduce absolute ‘off’ time was 8 mg/24 h. The AE profile was similar to previous studies.