Sleep in restless legs syndrome improves during opioid treatment – Results from a large 1-year multi-center trial

Abstract

Introduction In severe cases of restless legs syndrome (RLS), symptoms result in bothersome impact on sleep and impairment of daytime function. This study showed superior efficacy of oxycodone/naloxone prolonged-release fixed-combination (OXNPR) vs. placebo for the primary endpoint (International Restless Legs Syndrome Study Group Rating Scale (IRLS) total score) in severely affected RLS patients. The impact of RLS on sleep quality was assessed as a secondary endpoint. Materials and methods After screening and a 7-day washout, 304 patients (age 62iA11.2 years) with failed prior RLS therapy and an IRLS score iÝ21 were randomized to double- blind OXNPR bid (mean oxycodone dose 21.9iA15.0 mg/day) or placebo for 12 weeks. 197 patients participated in a 40-week open-label extension (mean oxycodone dose 18.1iA10.5 mg/day). Sleep was subjectively assessed by the Medical Outcomes Study (MOS) sleep scale, by item 4 of the IRLS (sleep disturbance due to RLS symptoms) and 4 questions of the RLS-6: Q1 (sleep satisfaction), Q2/3 (RLS symptom severity at falling asleep/during the night), and Q6 (daytime tiredness). Results MOS sleep scale results showed greater improvement in sleep quality for OXNPR vs. placebo; OXNPR-treated patients fell asleep more quickly, slept for longer, experienced less sleep disturbance and greater sleep adequacy than placebo- treated patients (p 0.001). The IRLS¨C item 4 showed that sleep disturbance was ’very severe’ at baseline (median = 4 on a scale of 0–4) but had improved to ’mild’ (median = 1) in the OXNPR group and severe (median = 3) in the placebo group at Week 12. These results support results for IRLS total score. The RLS-6 was scored on a 0–10 scale; higher values represent more severe symptoms. Patients were highly dissatisfied with sleep at baseline (score of 8.2iA2.0 for Q1), but improved with a score of 3.8iA3.1 for OXNPR at Week 12. Similarly, results for Q2 improved from 7.2iA2.6 to 2.7iA2.9, results for Q3 improved from 7.5iA2.4 to 2.8iA3.0 and results for Q6 improved from 6.4iA2.8 to 3.7iA3.0. The improvement was significantly larger for OXNPR than placebo (p 0.001). Conclusion In this analysis of an important secondary outcome measure, we demonstrated that treatment with OXNPR improves sleep quality in the context of an overall favorable treatment effect in severely affected RLS patients who failed on previous RLS medications. Acknowledgements Karen Paine provided medical writing services on behalf of Mundipharma Research. (Funded by Mundipharma Research; ClinicalTrials.gov number, NCT01112644).