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Richard K Bogan,1 Aaron Ellenbogen,2 Philip M Becker,3 Clete Kushida,4 Eric Ball,5 William G Ondo,6 Christine K Caivano,7 Sarah Kavanagh71SleepMed, Columbia, SC, 2Quest Research Institute, Farmington Hills, MI, 3Sleep Medicine Associates of Texas, Dallas, TX, 4Division of Sleep Medicine, Department of Psychiatry and Behavioral Sciences, Stanford Center for Human Sleep Research, Stanford, CA, 5Walla Walla Clinic, Walla Walla, WA, 6University of Texas Health Science Center, Houston, TX, 7Global Regulatory Affairs (CKC)* and Neurosciences MDC (SK), GlaxoSmithKline, Research Triangle Park, NC, USA*Development Sciences department at the time of the analysisPurpose: The aim of the study reported here was assessment of subjective and novel sleep endpoints, according to sleep disturbance severity at baseline, in adult subjects with moderate to severe primary restless legs syndrome (RLS) treated with gabapentin enacarbil (GEn) 1200 mg or placebo.Methods: Integrated analysis of two 12-week randomized trials in subjects with RLS was undertaken. Sleep outcomes from the Medical Outcomes Study (MOS) Sleep Scale and the Post Sleep Questionnaire were evaluated. Novel sleep endpoints derived from the 24-Hour RLS Symptom Diary were compared with similar endpoints derived from the Pittsburgh Sleep Diary (PghSD). Subjects were divided into two subgroups based on their level of sleep disturbance (responses to item 4 of the International Restless Legs Scale) at baseline. Data were analyzed using a last observation carried forward approach.Results: The modified intent-to-treat population comprised 427 subjects (GEn 1200 mg, n = 223; placebo, n = 204). GEn significantly improved all MOS Sleep Scale domain scores from baseline compared with placebo (P < 0.05) in both subgroups. Compared with placebo, GEn-treated subjects with very severe to severe sleep disturbance reported higher overall sleep quality, fewer nighttime awakenings, and fewer hours awake per night due to RLS symptoms at Week 12 on the Post Sleep Questionnaire (all P < 0.001, distribution of responses); sleep quality was the only significant item in those with moderate to no sleep disturbance (P < 0.0001). Evaluation of sleep endpoints derived from the 24-Hour RLS Symptom Diary and PghSD yielded similar results.Conclusion: Once-daily GEn 1200 mg significantly improves subjective sleep outcomes compared with placebo in subjects with RLS, regardless of the severity of sleep disturbance at baseline, although a greater improvement in sleep assessments may be observed in subjects with very severe to severe sleep disturbance than in those with moderate to no disturbance. Similar patterns were observed between treatment groups when comparing sleep endpoints derived from the PghSD and the novel sleep endpoints derived from the 24-Hour RLS Symptom Diary.Keywords: 24-Hour RLS Symptom Diary, Pittsburgh Sleep Diary, Medical Outcomes Study Sleep Scale, Post Sleep Questionnaire