Lemborexant superior to zolpidem for insomnia in elderly: JAMA

USA: Insomnia is prevalent in older adults and is associated with health risks in them. Now, according to a recent study published in the JAMA Network Open lemborexant therapy significantly improved sleep maintenance and sleep onset compared to placebo and zolpidem therapy in insomnia patients aged 55 years and older. Also, lemborexant therapy was well tolerated.

Insomnia disorder is characterized by the inability to maintain and/or initiate sleep for 3 nights or more for 3 months or longer. It is prevalent and associated with health risks in older adults. Existing treatments have efficacy and safety issues that create unmet needs in this patient population.

Russell Rosenberg, NeuroTrials Research, Atlanta, Georgia, and colleagues compared 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 is a global randomized double-blind parallel-group placebo-controlled active-comparator phase 3 study conducted across 67 sites in North America and Europe from May 31, 2016, to January 30, 2018. Ait involved 1006 participants aged 55 years and older with insomnia disorder confirmed by sleep history, sleep diary, and polysomnography. They were randomized to receive (placebo, n = 208; zolpidem tartrate extended-release (6.25 mg), n = 263; lemborexant 5 mg, n = 266; and lemborexant 10 mg, n = 269) for 1 month at bedtime.

Paired polysomnograms were collected at baseline, the first 2 nights, and the last 2 nights of treatment. The primary endpoint was the change from baseline in latency to persistent sleep for lemborexant therapy vs placebo.

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Key findings of the study include:

• 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 endpoint for least-squares geometric means treatment ratio vs placebo: for lemborexant 5 mg, 0.77; for lemborexant 10 mg, 0.72).


• For nights 29 and 30, as measured using polysomnography, the mean change from baseline in sleep efficiency (LSM treatment difference vs placebo for lemborexant 5 mg, 7.1% and for lemborexant 10 mg, 8.0%) and wake-after-sleep onset (least-squares mean treatment ratio vs placebo for lemborexant 5 mg, −24.0 min and for lemborexant 10 mg, −25.4 min) were significantly greater for both doses of lemborexant therapy compared with placebo.


• For nights 29 and 30, wake-after-sleep onset in the second half of the night (least-squares mean treatment difference vs zolpidem for lemborexant 5 mg, −6.7 min and for lemborexant 10 mg, −8.0 min) was significantly greater for both doses of lemborexant therapy compared with zolpidem therapy measured using polysomnography.


• Six participants (4 in the zolpidem group and 2 in the lemborexant 5 mg group) reported serious adverse events; none were treatment-related.


• Other adverse events were mostly mild or moderate in severity.

"In this randomized clinical trial, lemborexant therapy significantly improved both sleep onset and sleep maintenance, including in the second half of the night, compared with both placebo and zolpidem measured objectively using polysomnography. Lemborexant therapy was well tolerated," wrote the authors,

"Results of this first head-to-head phase 3 clinical trial are encouraging and support the continued development of lemborexant therapy for the treatment of insomnia disorder," they concluded.

The study, "Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia DisorderA Phase 3 Randomized Clinical Trial," is published in JAMA Network Open.

DOI: 10.1001/jamanetworkopen.2019.18254