A152 SLEEP, Volume 42, Abstract Supplement, 2019 B. Clinical Sleep Science and Practice I. Insomnia response extends into the post-arousal period thereby impact- ing other behaviors such as ambulating, memory, and cognitive function. Support (If Any): Investigator-initiated grant from Merck Sharp and Dohme Corp. 0373 EFFECTS OF SUVOREXANT ON SLEEP IN FIBROMYALGIA Gail Koshorek, Jelena Verkler, Dana Withrow, Thomas Roth, Timothy Roehrs Henry Ford Health System, Detroit, MI, USA. Introduction: The chronic pain disorder, fbromyalgia, is asso- ciated with sleep disturbance, typically sleep maintenance. Pharmacological treatment studies have either focused on the pain or the sleep disturbance with equivocal results in that few stud- ies have improved both sleep and pain. No studies have evaluated the effect of sleep medication on pain sensitivity. Suvorexant, an orexin antagonist, approved for treatment of insomnia may pro- vide beneft for both the sleep and pain of fbromyalgia.. Here we report on suvorexant’s sleep effects in patients with fbromyalgia and comorbid insomnia disorder gathered as part of a feasibility study. Methods: Women, 21- 65 yrs old, with fbromyalgia and co-morbid insomnia (n=10) were treated for 9 nights with suvorexant, 20 mg, and placebo with the order of the treatments counterbalanced. They were in good psychiatric and stable physical health and met American College of Rheumatology criteria for fbromyalgia and DSM-V criteria for insomnia. On a screening 8-hr PSG other pri- mary sleep disorders were ruled out. On nights 8 and 9 of each treatment 8-hr PSGs were collected. All PSGs were scored fol- lowing ASSM criteria and PSG measures were compared using repeated measures ANOVAs with night and drug condition as factors. Results: Suvorexant vs placebo increased total sleep time (7.2 vs 6.7 hrs, p< .05) and reduced wake after sleep onset (37 vs 67 min, p<.04) with no night effects or interaction. Suvorexant also reduced wake during the last half (20 vs 41 min, p< .03) and quarter (13 vs 20 min, p< .03) of the night. Latency to persistent sleep and sleep stage measures were not altered by suvorexant. Conclusion: In patients with fbromyalgia and comorbid in- somnia disorder suvorexant, 20 mg, improved total sleep time and reduced wake after sleep onset with sustained effects through the last quarter of the sleep period and no alteration of normal sleep staging. Support (If Any): Merck, grant #: 53918, awarded to Dr. Roehrs 0374 EFFECTS OF SUVOREXANT ON PAIN SENSITIVITY IN FIBROMYALGIA Dana Withrow, Jelena Verkler, Gail Koshorek, Thomas Roth, Timothy Roehrs Henry Ford Health System, Detroit, MI, USA. Introduction: The chronic widespread pain disorder, fbromyalgia, is known for its nociceptive hypersensitization and disturbed sleep. The relation of sleep and pain is bidirectional and data suggest that improving sleep in chronic pain disorders would attenuate daytime pain sensitivity. Here we report on suvorexant’s next-day pain effects following night-time use gathered as part of a feasi- bility study. Methods: Women, 21- 65 yrs old, with fbromyalgia and co-morbid insomnia (n=10) were treated for 9 nights with suvorexant 20 mg and placebo with the order of treatment nights counterbalanced. Subjects were in good psychiatric health and stable physical condi- tion and met American College of Rheumatology criteria for fbro- myalgia and DSM-V criteria for insomnia. On a baseline screening 8-hr PSG other primary sleep disorders were ruled out. On days 2 and 9 of each treatment condition pain sensitivity was assessed at 1100 and 1500 hr by measuring fnger withdrawal latency (FWL) to a radiant heat stimulus at 5 randomly presented intensity levels. FWL on the two tests of days 2 and 9 were compared between treatments using repeated measures ANOVAs with days and drug condition as factors. Results: FWL on both am and pm tests varied as a function of intensity (p<.001) with no time of day effects or interaction (hi in- tensity = short latency; low = long latency). On days 2 and 9 after suvorexant versus placebo pain sensitivity was reduced (i.e., latency increased). Average FWL (over 5 intensities and both days) was increased on both the am test (13.9 vs 13.1 sec) and pm tests (15.8 vs 14.1 sec, p<.03) following suvorexant the previous night. There were no time of day effects or interaction. Conclusion: Following hypnotic use of suvorexant 20 mg versus placebo by patients with fbromyalgia, next-day pain sensitivity was reduced on both am and pm assessments of FWL to a radiant heat stimulus. Support (If Any): Merck, grant #: 53918, awarded to Dr. Roehrs. 0375 A NOVEL DUAL OREXIN RECEPTOR ANTAGONIST (ACT-541468) TO TREAT INSOMNIA: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, ACTIVE- REFERENCE PHASE 2 STUDY Yves Dauvilliers 1 , Gary Zammit 2 , Ingo Fietze 3 , David Mayleben 4 , Dalma Seboek Kinter 5 , Scott Pain 5 , Jan Hedner 6 1 Sleep and Wake Disorders Centre, Department of Neurology, Gui de Chauliac Hospital, Montpellier cedex, France, 2 Clinilabs Drug Development Corporation, New York, NY, USA, 3 Center of Sleep Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany, 4 CTI Clinical Research Center, Cincinnati, OH, USA, 5 Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland, 6 Department of Sleep Medicine, Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, Sweden. Introduction: Orexins are involved in the regulation of sleep and wakefulness. The primary objective of this Phase 2 study was to investigate the dose-response relationship of ACT-541468 on sleep variables in subjects with insomnia disorder. Methods: Eligible adults (≤64 years) with insomnia disorder (Diagnostic and Statistical Manual of Mental Disorders, 5 th Edition criteria) were randomized (1:1:1:1:1:1) to receive, 5, 10, 25, and 50 mg ACT-541468, placebo or 10 mg zolpidem for 4 weeks. Main effcacy endpoints were the change from baseline (placebo run-in) to Days1&2 for wake after sleep onset (WASO; primary) and latency to persistent sleep (LPS; secondary). The dose-response of ACT-541468 was evaluated using MCP-Mod methodology. Results: Of 1005 subjects screened, 360 (median age 47 [range, 36-53]; 64% female) were randomized. A signifcant dose-response of ACT-541468 was demonstrated for WASO (p≤0.0007). Observed mean reductions from baseline to Days 1&2 for WASO were −28.99, −33.75, −39.64, and −45.49 min for ascending ACT-541468 doses Downloaded from https://academic.oup.com/sleep/article/42/Supplement_1/A152/5451490 by guest on 04 January 2024