Medline ® Abstracts for References 36,37

BACKGROUND: Long-term efficacy and tolerability data are not yet available for patch formulations of dopamine agonists in restless legs syndrome.

METHODS: Efficacy and safety of rotigotine (0.5-4mg/24h), formulated as a once-daily transdermal system (patch), were investigated in an open extension (SP710) of a preceding 6-week placebo-controlled trial (SP709, 341 randomized patients) in patients with idiopathic restless legs syndrome. For efficacy assessment the international RLS severity scale (IRLS), the RLS-6 scales, the clinical global impressions (CGI) and the QoL-RLS questionnaire were administered. In addition, long-term tolerability and safety were assessed.

RESULTS: Of 310 patients who finished the controlled trial, 295 (mean age 58+/-10 years, 66% females) with a mean IRLS score of 27.8+/-5.9 at baseline of SP709 were included. We report results after one year of this ongoing long-term trial. Two hundred twenty patients (retention rate=74.6%) completed the 12-month follow-upperiod. The mean daily dose was 2.8+/-1.2mg/24h with 4mg/24h (40.6%) being the most frequently applied dose; 14.8% were sufficiently treated with 0.5 or 1.0mg/24h. The IRLS total score improved by ?17.4+/-9.9 points between baseline and end of Year 1 (p<0.001). The other measures of severity, sleep satisfaction and quality of life supported the efficacy of rotigotine (p<0.001 for pre-post-comparisons of all efficacy variables). The tolerability was described as "good" or "very good" by 80.3% of all patients. The most common adverse events were application site reactions (40.0%), which led to withdrawal in 13.2%. Further relatively frequent adverse events were nausea (9.5%) and fatigue (6.4%). Two drug-related serious adverse events, nausea and syncope, required hospitalization. Symptoms of augmentation were not reported by the patients.

CONCLUSION: Rotigotine provided a stable, clinically relevant improvement in all efficacy measures throughout one year of maintenance therapy. The transdermal patch was safe and generally well tolerated by the majority of patients. Comparable to any transdermal therapy, application site reactions were the main treatment complication.

BACKGROUND: Rotigotine is a unique dopamine agonist with activity across D1 through D5 receptors as well as select adrenergic and serotonergic sites. This study reports the 2-year follow-up safety and efficacy data of an ongoing open-label multicenter extension study (NCT00498186) of transdermal rotigotine in patients with moderate to severe restless legs syndrome (RLS).

METHODS: Patients received a once-daily patch application of an individually optimized dose of rotigotine between 0.5 mg/24 h to 4 mg/24 h. Safety assessments included adverse events (AEs) and efficacy was measured by the International RLS Study Group Severity Rating Scale (IRLS), RLS-6 scales and Clinical Global Impression (CGI). Quality of life (QoL) was measured by QoL-RLS.

RESULTS: Of 310 patients who completed a 6-week placebo-controlled trial (SP709), 295 (mean age 58±10 years, 66% females) were included in the open-label trial SP710. 64.7% (190/295 patients) completed the 2-year follow-up; 29 patients discontinued during the second year. Mean daily rotigotine dose after 2 years was 2.93±1.14 mg/24 h with a 2.9% dose increase from year 1. Rotigotine was generally well tolerated. The rate of typical dopaminergic side effects, nausea and fatigue, was low (0.9% and 2.3%, respectively) during the second year; application site reactions were frequent but lower than in year 1 (16.4% vs. 34.5%). The IRLS total score improved from baseline of SP709 (27.8±5.9) by 17.2±9.2 in year 2 completers. Similar improvements were observed in RLS-6 scales, CGI scores and QoL-RLS. The responder rate in the CGI change item 2 ("much" and "very much" improved) was 95% after year 2.

CONCLUSIONS: Transdermal rotigotine is an efficacious and well-tolerated long-term treatment option for patients with moderate to severe RLS with a high retention rate during 2 years of therapy.

TRIAL REGISTRATION: NCT00498186.