UCB today announced the results of a 6-month, randomized, double-blind, placebo-controlled clinical study, published in the journal Movement Disorders, showing that Neupro® (rotigotine transdermal system, 2 and 3 mg/24 hours) provided sustained, clinically relevant improvements in symptoms of Restless Legs Syndrome (RLS). The study also showed high rates of complete remission seen with rotigotine 2 mg or 3 mg/24 hours.
“In this study rotigotine alleviated RLS symptoms in patients with moderate to severe RLS over a treatment period of six months, which is the longest reported double-blind treatment period maintained in the U.S. for the evaluation of RLS treatments,” said Dr. Richard Allen, from Department of Neurology, John Hopkins University, Baltimore, Md., U.S. “One result from this study was a high rate of complete remission from all RLS symptoms. Approximately one of three previously moderately to severely ill patients was without any RLS symptoms after 6 months of treatment with either 2 or 3 mg of rotigotine.”
In the 6-month, double-blind study, 505 patients with moderate to severe RLS were randomized to receive either placebo or rotigotine (0.5, 1, 2, 3 mg/24 hours) by transdermal administration, of whom 494 patients (98%) were included in the modified intention-to-treat (mITT) analysis. The two co-primary efficacy endpoints were decreased from baseline to end of maintenance in International Restless Legs Syndrome (IRLS) sum score and in Clinical Global Impressions (CGI-1) score. The IRLS sum score ranges from 0 (no symptoms) to 40 (very severe symptoms) and the CGI-1 from 1 (not ill at all) to 7 (extremely ill). Secondary efficacy variables included the proportion of treatment responders for IRLS and CGI-1.
On both primary efficacy measures, rotigotine 2 and 3 mg/24 hour was shown to produce a statistically significant and clinically relevant improvement compared to placebo (p < 0.001), with sustained improvement observed throughout the six months of maintenance. Treatment differences between placebo and rotigotine for the IRLS sum score were -4.5 (95% Confidence Interval: -6.9, -2.2) for 2 mg/24 hour rotigotine, -5.2 (95% Confidence Interval: -7.5, -2.9) for 3 mg/24 hour rotigotine, and for CGI-1 -0.65 (95% Confidence Interval: -1.0, -0.3) and -0.9 (95% Confidence Interval: -1.3, -0.5) for the 2 and 3 mg/24 hour doses, respectively. Reductions in IRLS sum score and CGI-1 score were also seen with rotigotine 0.5 and 1 mg/24 hours, but differences from placebo were not statistically significant.
Secondary efficacy variables for IRLS or CGI-1 responders were defined by a minimum 50% improvement in the respective score at end of maintenance versus baseline. A total of 56.6% of all subjects receiving rotigotine were considered responders for the IRLS and 49.8% for CGI-1 score. In all rotigotine groups, responder rates were higher than in the placebo group and statistical significance was reached for the 1, 2 and 3 mg/24 hour doses. The number of patients needed to be treated with rotigotine instead of placebo for one of the patients to be classified as an IRLS responder was 4.4 and 3.4 for 2 and 3 mg/24 hour rotigotine, respectively, with similar numbers for CGI-1. An IRLS score of 0 (no symptoms) was documented for 9.1% of placebo and 23.3% of all rotigotine subjects (16.3% for 0.5 mg/24 hour, 17.2% for 1 mg/24 hour, 30.5% for 2 mg/24 hour and 29.1% for 3 mg/24 hour) with a number needed to treat of 4.7 for 2 mg/24 hour and 5.0 for 3 mg/24 hour rotigotine.
Most adverse events (AEs) were mild to moderate in intensity, the most common AEs being application site reactions (27% rotigotine versus 5% placebo), nausea (18.1% rotigotine versus 10% placebo) and headache (11.6% rotigotine versus 8% placebo).
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