Efficacy of rotigotine transdermal system in severe restless legs syndrome: a randomized, double-blind, placebo-controlled, six-week dose-finding trial in Europe.

Abstract

BACKGROUND:

In a pilot placebo-controlled study, low dosages of 0.5-2mg/24h rotigotine showed a dose-dependent beneficial effect in restless legs syndrome (RLS) patients.

METHODS:

Efficacy and safety of the dopamine agonist rotigotine, formulated as a once-daily transdermal system (patch), was investigated for five fixed dosages and compared to placebo in patients with idiopathic RLS in a double-blind, randomized, parallel-group, multicenter, six-week dose-finding trial. Primary efficacy measure was the total score of the International RLS Severity Scale (IRLS); in addition, the RLS-6 scales and the Clinical Global Impressions (CGI) were administered.

RESULTS:

Of 371 enrolled patients, 341 patients (mean age 58+/-10years, 67% females) were randomized. The IRLS total score improved between baseline and end of the six-week treatment period by -10.6 (0.5mg/24h rotigotine; patch area 2.5cm2), -15.1 (1mg/24h; 5cm2), -15.7 (2mg/24h; 10cm2), -17.5 (3mg/24h; 15cm2), and -14.8 (4mg/24h, 20cm2) as compared to placebo (-9.2). The hierarchical statistical test procedure demonstrated superiority of rotigotine over placebo for 4mg/24h, 3mg/24h, 2mg/24h, and 1mg/24h, with p-values of 0.0013, <0.0001, 0.0003, and 0.0004, respectively. Only the 0.5mg/24h dose was not different compared to placebo (p=0.2338). The CGI and the RLS-6 severity items supported the efficacy of the rotigotine doses beyond 0.5mg/24h. The most frequent side effects were application site reactions and nausea and tended to be more frequent with higher doses.

CONCLUSIONS:

This dose-finding trial identified the range for a maintenance dose of rotigotine from 1mg/24h to 3mg/24h. The lowest dose was ineffective and, with the highest dose, no additional benefit was observed.

• Authors: Wolfgang H Oertel, Heike Benes, Diego Garcia-Borreguero, Peter Geisler, Birgit Högl, Bernd Saletu, Claudia Trenkwalder, Kenneth W Sommerville, Erwin Schollmayer, Ralf Kohnen, Karin Stiasny-Kolster, Rotigotine SP 709 Study Group
• Journal: Sleep medicine (Sleep Med) Vol. 9 Issue 3 Pg. 228-39 (Mar 2008) ISSN: 1389-9457 [Print] Netherlands
• PMID: 17553743 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Agonists
• Tetrahydronaphthalenes
• Thiophenes
• rotigotine

Topics

• Administration, Cutaneous
• Adult
• Aged
• Dopamine Agonists (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Europe
• Female
• Humans
• Male
• Middle Aged
• Restless Legs Syndrome (diagnosis, drug therapy)
• Tetrahydronaphthalenes (administration & dosage, adverse effects)
• Thiophenes (administration & dosage, adverse effects)
• Treatment Outcome