Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: A Phase 3 Randomized Clinical Trial

• Published in: JAMA network open 2019-12, Vol.2 (12), p.e1918254-e1918254
• Main Authors: Rosenberg, Russell, Murphy, Patricia, Zammit, Gary, Mayleben, David, Kumar, Dinesh, Dhadda, Shobha, Filippov, Gleb, LoPresti, Antonia, Moline, Margaret
• Format: Article
• Language: English
• Subjects: Aged; Clinical trials; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Hypnotics and Sedatives - therapeutic use; Insomnia; Male; Middle Aged; Neurology; Older people; Online Only; Original Investigation; Polysomnography; Pyridines - therapeutic use; Pyrimidines - therapeutic use; Sleep; Sleep Aids, Pharmaceutical - therapeutic use; Sleep Initiation and Maintenance Disorders - drug therapy; Zolpidem - therapeutic use
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2019.18254

Insomnia disorder is prevalent and associated with health risks in older adults; however, efficacy and safety issues with existing treatments create significant unmet needs in this patient population. To compare treatment with the orexin receptor antagonist lemborexant with placebo and zolpidem tartrate extended release in participants with insomnia disorder. The Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1) clinical trial was a global randomized double-blind parallel-group placebo-controlled active-comparator phase 3 study conducted at 67 sites in North America and Europe from May 31, 2016, to January 30, 2018. Data analyses were conducted from January 31, 2018, to September 10, 2018. Participants were 55 years and older with insomnia disorder characterized by reported sleep maintenance difficulties and confirmed by sleep history, sleep diary, and polysomnography. Participants could have also had sleep onset difficulties. Participants received placebo, zolpidem tartrate extended release (6.25 mg), or lemborexant (5 mg or 10 mg) for 1 month at bedtime. Paired polysomnograms were collected at baseline, the first 2 nights, and the last 2 nights of treatment. The primary end point was the change from baseline in latency to persistent sleep for lemborexant therapy vs placebo. Key secondary end points were changes from baseline in sleep efficiency and wake-after-sleep onset compared with placebo, and wake-after-sleep onset in the second half of the night compared with zolpidem therapy. Among 1006 participants randomized (placebo, n = 208; zolpidem, n = 263; lemborexant 5 mg, n = 266; and lemborexant 10 mg, n = 269), 869 (86.4%) were women and the median age was 63 years (range, 55-88 years). Both doses of lemborexant therapy demonstrated statistically significant greater changes from baseline on objective sleep onset as assessed by latency to persistent sleep (log transformed) that was measured using polysomnography at the end of 1 month of treatment (nights 29 and 30) compared with placebo (primary end point for least squares geometric means treatment ratio vs placebo: for lemborexant 5 mg, 0.77; 95% CI, 0.67-0.89; P