Rotigotine effects on early morning motor function and sleep in Parkinson's disease: A double‐blind, randomized, placebo‐controlled study (RECOVER)

Abstract

In a multinational, double-blind, placebo-controlled trial (NCT00474058), 287 subjects with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control were randomized 2:1 to receive rotigotine (2–16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks. Early-morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinson's Disease Sleep Scale (PDSS-2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by −7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by −3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS-2 total score had decreased by −5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by −1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: −3.55 [95% confidence interval (CI) −5.37, −1.73]; P = 0.0002) and PDSS-2 (treatment difference: −4.26 [95% CI −6.08, −2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances. © 2010 Movement Disorder Society

Sleep disturbances in Taiwanese patients with Parkinson's disease

“…Both were closely related to the disease per se of PD. Some researchers also regrouped different items into special domains to explore aspects of nocturnal disturbance of specific interest (Ray Chaudhuri et al., 2012; Trenkwalder et al., 2011). Therefore, we categorized individual item into five domains to illustrate the different characteristics in the 15 items, and to correlate each domain with nighttime and daytime sleep problems (Table 1).…”

Safety and Efficacy of Rotigotine for Treating Parkinson’s Disease: A Meta-Analysis of Randomised Controlled Trials

“…Trenkwalder et al performed a placebocontrolled, double-blind, multinational trial and found that rotigotine could significantly improve the modified Parkinson's Disease Sleep Scale (PDSS-2) and UPDRS Part III scores in comparison with the placebo 10 . Patients, who received the maximum dose of rotigotine, exhibited a significantly improved UPDRS Part I, II and III scores, indicating that rotigotine is effective, safe and well-tolerated for the treating patients with early-stage PD 25,30 .…”

“…Nicholas et al also reported higher incidence of AEs, including dry mouth, application-site reactions, dyskinesia and nausea, in the rotigotine group (8 mg/24 h) than in the placebo group 26 . Furthermore, Trenkwalder et al found that the most common AEs were nausea (rotigotine, 21% and placebo, 9%), dizziness (rotigotine 10% and placebo, 6%) and applicationsite reactions (rotigotine, 15% and placebo, 4%) 10 . These results indicate that rotigotine has higher incidence of AEs.…”

“…rotigotine), levodopa and MAO-B inhibitors 7 . Rotigotine, which is delivered by a transdermal patch, is administered once daily; is safe and can improve symptoms, such as motor difficulties, in patients with early PD [8][9][10][11] . At the same time, the rotigotine transdermal system may also relieve nonmotor symptoms including fatigue, anhedonia, apathy and depression in patients with PD 12 .…”

Unmet needs in Parkinson's disease: New horizons in a changing landscape

“…Although some evidence supports the efficacy of certain treatments for depression, dementia, psychosis, constipation, orthostatic hypotension and sialorrhea, there is insufficient evidence for efficacious treatments for other important non-motor symptoms that certainly contribute to poor quality of life, such as neurogenic bladder disturbance, erectile dysfunction, fatigue, insomnia, apathy, anxiety and excessive daytime sleepiness [60,63]. The emergence of recent controlled trials concentrated on key non-motor issues such as Parkinson associated pain [64] or sleep [65] is highly encouraging. Nevertheless, the broad spectrum of NMS in PD clearly highlight the need for developing non-dopaminergic therapies that target the nondopaminergic degeneration in PD.…”