Effects of rotigotine on daytime symptoms in patients with primary restless legs syndrome: a randomized, placebo-controlled study

Abstract

Objective:

This 12 week double-blind, placebo-controlled study (ClinicalTrials.gov: NCT01569464) was conducted to evaluate the effects of rotigotine transdermal patch on daytime symptoms in patients with idiopathic restless legs syndrome (RLS).

Methods:

Adult patients with moderate-to-severe RLS were randomized to rotigotine (optimal dose: 1–3 mg/24 h) or placebo. A modified four-assessment version (4:00 pm, 6:00 pm, 8:00 pm, and 10:00 pm) of the Multiple Suggested Immobilization Test (m-SIT) was performed at baseline and end of 4 week maintenance (EoM). Primary study outcomes were change from baseline to EoM in International Restless Legs Syndrome Rating Scale (IRLS) and in average of means for the m-SIT Discomfort Scale (m-SIT-DS) (combined average of mean values from each of the individual assessments). Secondary outcomes included average of means of Periodic Limb Movement during Wakefulness Index (PLMWI; PLM/hour) for the combination of m-SIT.

Results:

A total of 150 patients were randomized and 137 (rotigotine: 92/101 [91.1%]; placebo: 45/49 [91.8%]) completed maintenance. All 150 randomized patients were assessed for efficacy. At EoM, mean change in IRLS was −14.9 ± 9.3 with rotigotine vs. −12.7 ± 7.6 with placebo (ANCOVA, LS mean treatment difference [95% CI]: −0.27 [−2.96, 2.42]; p = 0.8451). Changes in average of means of m-SIT-DS values of each individual SIT were comparable with rotigotine (−2.68 ± 2.31) vs. placebo (−2.62 ± 2.61) (ANCOVA, LS mean treatment difference [95% CI]: 0.07 [−0.61, 0.75]; p = 0.8336) and comparable reductions in PLMWI were observed in both treatment groups (8.34 [−8.50, 25.17]; p = 0.3290). Rotigotine was generally well tolerated. Application site reactions (rotigotine: 20 patients [19.8%]; placebo: 4 [8.2%]) and nausea (16 [15.8%]; 3 [6.1%]) were the most common AEs.

Conclusions:

Rotigotine was beneficial in improving overall RLS symptom severity (assessed by IRLS) and RLS symptom severity at various times of the day (m-SIT-DS); however, superiority to placebo was not established.

Keywords: :

• Dopamine receptor agonist
• Periodic limb movements
• Restless legs syndrome
• Rotigotine

Transparency

Declaration of funding

This study was supported by UCB Pharma, Monheim am Rhein, Germany. All costs associated with manuscript development and publication were met by the sponsor.

Declaration of financial/other relationships

D.G.-B. has disclosed that he has served as a consultant for UCB Pharma, Xenoport, and Merck, and has received grants from UCB Pharma and Pfizer. R.A. has disclosed that he has served as board member for UCB Pharma, GlaxoSmithKline, Pfizer, Jazz Pharma, and Boehringer Ingelheim, and as a consultant for Pfizer, GlaxoSmithKline, Xenoport, Luitpold Pharma, and Neurogen. He has received grants from Pharmacosmos and GlaxoSmithKline, and speakers fees from UCB Pharma, EMD Serono, Pharmacosmos and Boehringer Ingelheim. J.H. has disclosed that he is a speaker for UCB Pharma and Jazz Pharmaceuticals. E.D., F.G. and K.M. have disclosed that they are employees of UCB Pharma and receive stock options. E.S. and R.S. have disclosed that they are employees of UCB Pharma. J.W. has disclosed received personal compensation for consulting from UCB Pharma, personal compensation and stock options for consulting from FlexPharma, personal compensation for serving on scientific advisory boards from Merck and Insys, for writing from UpToDate, and for serving as an expert witness from CantorColburn. He has also received financial support for research activities from UCB Pharma, NeuroMetrix, and Purdue.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Writing and editorial assistance was provided by Hannah Carney PhD (Evidence Scientific Solutions, London, UK) and contracted by UCB Pharma, Brussels, Belgium. Publication coordination was provided by Cédric Laloyaux (Global Publications Manager CNS, UCB Pharma, Brussels, Belgium). The authors also thank the patients, in addition to the investigators and their teams who contributed to this study.