Medical Reading

Rotigotine Transdermal System Shows Significant Symptom Reduction And Tolerability In Patients With Restless Legs Syndrome

November 03, 2017

UCB, Inc. presented results from two Phase III pivotal trials and one open-label extension trial of rotigotine transdermal system for the treatment of moderate-to-severe restless legs syndrome (RLS). These rotigotine data showed significant drops in RLS symptoms, including changes of up to 8 points over placebo using the International Restless Legs Syndrome Study Group Rating Scale (IRLS) and a reduction in disease severity over a two-year period.

"Given the strong efficacy and tolerability seen to date, rotigotine, if approved, would provide a new and valuable alternative for many patients negatively impacted by the symptoms of moderate-to-severe RLS," said Wayne Hening, M.D., a lead study investigator and Assistant Clinical Professor of Neurology at the Robert Wood Johnson Medical School.

In the two six-month, double-blind, placebo-controlled trials, rotigotine produced clinically relevant and statistically significant reductions in RLS symptoms compared to placebo and was generally well-tolerated. An additional presentation highlighted a two-year interim analysis of a long-term, open-label extension of rotigotine for moderate-to-severe RLS, representing some of the longest safety follow-up information for a dopamine agonist in RLS to date.

In these studies, the efficacy of rotigotine was evaluated by monitoring several clinician-administered scales including the IRLS, the Clinical Global Impressions (CGI) and the Restless Leg Syndrome-6 (RLS-6). The IRLS scale measures the severity and frequency of RLS symptoms and the degree to which they affect sleep and daily life (IRLS: 0 = no symptoms and 40 = very severe symptoms). The CGI scale measures the general severity of an illness, clinical improvement or efficacy of treatment parameters. On the RLS-6 scale, patients rate the severity of their RLS at four periods during the night and day, as well as sleep satisfaction and daytime tiredness.

A synopsis of rotigotine RLS clinical data presented at the meeting follows.

Six-Month Studies in Patients with Moderate-to-Severe Idiopathic RLS

SP 790
- In a multi-center, double-blind, placebo-controlled, Phase III trial, 458 patients were studied in eight European countries

- Rotigotine was studied in doses of 1, 2 and 3 mg/24 hours over a period of six months

- The study showed a statistically significant improvement in the IRLS sum score and a clinically relevant reduction in the CGI Item-1 (severity of illness) score compared to placebo

- The mean baseline scores were: IRLS 28.1 ± 6.1 and CGI 5.0 ± 0.8 reflecting moderate-to-severe symptoms at baseline

- The net effects over placebo after 6 months of treatment were 5.1 ± 1.3, -7.5 ± 1.3, and -8.2 ± 1.3 in the IRLS and -0.76 ± 0.19, -1.07 ± 0.19 and -1.21 ± 0.19 in CGI Item-1 for rotigotine 1, 2, and 3 mg/24 hours respectively (p < 0.001 for all comparisons)

- Rotigotine was also shown to be generally well-tolerated

- The most common adverse events that were determined by the investigators to be drug-related were application site reactions, nausea, headache and dizziness

SP 792
- In a multi-center, double-blind, placebo-controlled, Phase III trial, 505 patients were studied in the United States

- Rotigotine was studied at doses of 0.5, 1, 2 and 3 mg/24 hours over a period of six months, with all doses showing improvement over placebo

- Rotigotine, in doses of 2 and 3 mg/24 hours over a period of six months, resulted in a statistically significant improvement in IRLS sum score and a clinically relevant reduction in the CGI Item-1 (severity of illness) score compared to placebo

- The mean baseline scores were: IRLS 23.3 ± 5.0 and CGI 4.7 ± 0.7, reflecting moderate-to-severe symptoms at baseline

- The net effects over placebo after six months of treatment were -2.2 ± 1.2, 2.3 ± 1.2, -4.5 ± 1.2 (p