期刊
JOURNAL OF PARKINSONS DISEASE
卷 4, 期 3, 页码 361-373出版社
IOS PRESS
DOI: 10.3233/JPD-130320
关键词
Parkinson's disease; randomized controlled trial; dopamine receptor agonist; dose-response relationship; rotigotine
资金
- Michael J. Fox Foundation Therapeutic Development Initiative awarded to FPRT Bio, Inc.
- Emory
- NIEHS T32 (CJB) [5T32ES012870-10]
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.
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