A combination of extended-release oxycodone-naloxone significantly improved the symptoms of restless legs syndrome among patients who had failed first-line therapy, in a double-blind, randomized placebo-controlled study.
By the end of 12 weeks, 57% of patients randomized to the treatment group were considered responders, compared with 31% of patients in the placebo group, and 42% of patients in the treatment group had remission of symptoms, vs. 19% in the placebo group, Dr. Claudia Trenkwalder and her colleagues reported (Lancet Neuro 2013;12:1141-50). All of these differences were statistically significant.
"Our findings suggest a new, much-needed, option for management of severe restless legs syndrome for patients who cannot tolerate dopaminergic drugs," for nonresponders, and for those who developed tolerance or augmentation when receiving dopaminergic medications, wrote Dr. Trenkwalder of the department of neurosurgery, University of Göttingen (Germany) and her colleagues.
The study randomized 304 patients with severe restless legs syndrome (RLS) to either placebo (154) or to prolonged-release oxycodone-naloxone (150). The starting dose was 5 mg oxycodone with 2.5 mg naloxone twice a day. This could be titrated up to a maximum of 40 mg oxycodone with 20 mg naloxone twice a day. A 40-week open-label extension trial followed.
Patients had a mean disease duration of 10 years. All had failed first-line therapy with a dopaminergic drug. The mean International RLS Study Group symptom severity score was 31.6 on a 40-point scale, with 40 points corresponding to very severe symptoms. Change on this scale was the primary endpoint.
Of the entire 304 patients, 204 completed the 12-week randomized trial. Significantly more dropouts occurred in the treatment group (13% vs. 7%).
The mean daily dose was 22 mg hydrocodone with 11 mg naloxone. Ten patients took the maximum dose at some point during the study.
Symptoms began to decrease after 1 week among those taking the study drug. By 12 weeks, the symptom score had decreased a mean of 16.6 points in the treatment group and 9.5 points in the placebo group.
During this part of the study, 13% of the active group and 7% of the placebo group withdrew because of adverse events. The most common side effects were fatigue, constipation, nausea, and headache.
There were 197 patients who entered the extension phase; 157 of these completed the 40-week treatment period. At the end of the extension phase, 43% were classified as being in remission, with 22% having no symptoms at all.
The investigators cautioned that the study does not support using oxycodone-naloxone as a first-line therapy for RLS.
The study was sponsored by Mundipharma Research. Dr. Trenkwalder is a consultant for the company and reported financial relationships with numerous pharmaceutical companies. Three of the study’s coinvestigators are also Mundipharma employees, and several coinvestigators reported relationships with numerous pharmaceutical companies.