Effect Of Rotigotine Transdermal System On Nocturnal Blood Pressure Changes Associated With Periodic Limb Movements During Sleep In Patients With Restless Legs Syndrome (P5.268)
2014-04-08

OBJECTIVE: Examine the effect of rotigotine transdermal system (rotigotine) on nocturnal systolic BP (NSBP) elevations associated with periodic leg movements (PLM) during sleep in patients with moderate-to-severe restless legs syndrome (RLS). BACKGROUND: RLS is a common neurologic disorder associated with increased cardiovascular morbidity and mortality. NSBP elevations triggered by PLM, a key RLS symptom, have been identified as risk factors. DESIGN/METHODS: This double-blind, placebo-controlled study (SP0977 ENCORE [NCT01455012]) randomized patients with RLS (IRLS蠅15) 1:1 to optimal dose rotigotine (1-3mg/24h) or placebo. Continuous beat-to-beat BP and heart rate (HR) assessments were performed at baseline and end of 4-week maintenance (EoM). Primary outcome was change from baseline to EoM in PLM-associated NSBP elevations (defined: a slope of linear regression 蠅2.5 over 5 consecutive heartbeats [equivalent to 蠅10mmHg]). Secondary outcomes included change in total NSBP elevations, and PLM-associated nocturnal diastolic BP (NDBP) and HR elevations. Efficacy data are reported for the full analysis set (FAS). RESULTS: 81 patients (mean±SD age:57.2±10.5 years; 63% female) were randomized; 66 comprised the FAS (rotigotine:37; placebo:29). Reductions from baseline (~300 elevations) in PLM-associated NSBP elevations were greater with rotigotine vs placebo (LS mean [95% CI] -239.95 [-275.34,-204.56] vs -79.61[119.25,-39.97]; difference: -160.34[-213.23,-107.45]; p<0.0001). Greater decreases from baseline (~785 elevations) to EoM in total NSBP elevations also were observed for rotigotine vs placebo (difference: -161.13 [-264.47,-57.79]; p=0.0028). Consistent results were observed for the change from baseline to EoM in number of PLM-associated NDBP and HR elevations in rotigotine-treated patients vs placebo. The adverse event profile was similar to previous rotigotine studies. 15 patients (rotigotine:4/40; placebo:11/41) discontinued prematurely. CONCLUSIONS: Rotigotine reduced the number of PLM-associated NSBP, NDBP and HR elevations, and total NSBP elevations in patients with RLS. Further investigation is required to determine whether the observed decreases in PLM-related BP and HR elevations with rotigotine translate into reductions in cardiovascular risk in patients with RLS. Study Supported by: UCB Pharma Disclosure: Dr. Oertel has received personal compensation for activities with Boehringer Ingelheim Pharmaceuticals Inc., Cephalon, Merck & Co. Inc., Merck Sharp & Dohme Ltd., Merck Serono, Mundipharma, Novartis, Schwarz Pharma, Neuroscience /UCB Pharma, Pfizer Inc., Synovia, Teva Neuroscience, and Desitin. Dr. Oertel holds stock and/or stock options in Roche Diagnostics Corp. which sponsored research in which Dr. Oertel was involved as an investigator. Dr. Oertel has received research support from UCB Pharma, Teva Neuroscience, International Parkinson Foundation, and the Michael J Fox Foundation. Dr. Bauer has received personal compensation for activities with UCB Pharma. Dr Bauer has received research support from Medtronic, Inc. Dr. Cassel has received personal compensation for activities with UCB Pharma. Dr. Rye has received personal compensation for activities with UCB Pharma and Jazz Pharmaceuticals. Dr. Walters has received personal compensation for activities with UCB Pharma. Dr. Walters has received research support from UCB Pharma and Mundi Pharma. Dr. Winkelman has received personal compensation for activities with UCB Pharma and Xenoport Inc. as a consultant. Dr. Winkelman has received research support from GlaxoSmithKline Inc., and UCB Pharma. Dr. Bauer has received personal compensation for activities with UCB Biosciences GmbH. Dr. Joeres has received personal compensation for activities with UCB Pharma. Dr. Grieger has received personal compensation for activities with UCB Pharma as an employee. Dr. Moran has received personal compensation for activities with UCB Pharma as an employee. Dr. Schollmayer has received personal compensation for activities with UCB Pharma. Dr. Whitesides has received personal compensation for activities with UCB Pharma as an employee. Dr. Whitesides has held stock and/or stock options in UCB Pharma, which sponsored research in which Dr. Whitesides was involved as an investigator. Dr. Trenkwalder has received personal compensation for activities with Solvay S.A., Schwarz Pharma, Boehringer Ingelheim Pharmaceuticals Inc., GlaxoSmithKline Inc., Cephalon Inc., Lundbeck Research USA, Inc., Vifor Pharma, Axxonis Pharma, Teva Nueroscience, Britannia, Novartis, and Mundipharma. Dr. Trenkwalder has received research support from Teva Neuroscience, Boehringer Ingelheim Pharmaceuticals Inc., the Michael J. Fox Foundation, and the German Research Council (BMBF).