Investigators test a new drug for geriatric patients with insomnia disorder.
Margaret Moline, PhD
A team led by Margaret Moline, PhD, Executive Director, Neurology Business Group, Eisai, investigated whether lemborexant, an orexin receptor antagonist, can treat insomnia disorder in geriatric patients compared to a placebo and zolpidem tartrate extended release therapy.
In the randomized double-blind clinical study, the investigators looked at 1006 patients at least 55 years old with insomnia disorder.
The study took place at 67 sites in North America and Europe between May 31, 2016 and January 30, 2018.
Insomnia disorder was characterized by reported sleep maintenance difficulties and was confirmed by sleep history, sleep diary, and polysomnography. Patients also may have had sleep onset difficulties.
In the study, patients received either 5 or 10 mg of lemborexant, a placebo, or 6.25 mg of zolpidem tartrate extended release for 1 month at bedtime (placebo, n = 208; zolpidem, n = 263; lemborexant 5 mg, n = 266; and lemborexant 10 mg, n = 269). The investigators used paired polysomnograms at baseline, the first 2 nights of treatment, and the last 2 nights.
The primary endpoint of the study was the change from baseline in latency to persistent sleep for lemborexant therapy when compared with placebo. Some of the secondary endpoints included changes from baseline in sleep efficiency and wake-after-sleep onset compared with placebo, as well as wake-after-sleep onset in the second half of the night compared with zolpidem therapy.
“Lemborexant therapy significantly improved both latency to persistent sleep and sleep maintenance (wake-after-sleep onset and sleep efficiency) compared objectively via polysomnography with both placebo and zolpidem tartrate extended release therapy,” the authors wrote. “Efficacy was also demonstrated on patient-reported end points of sleep onset, sleep efficiency, and wake-after-sleep onset for both doses of lemborexant compared with placebo.”
Both 5 and 10 mg of lemborexant therapy showed substantially greater changes from baseline on objective sleep onset as assessed by latency to persistent sleep measured using polysomnography at the end of 1 month of treatment compared with placebo (primary end point for least squares geometric means (LSM) treatment ratio vs placebo: for lemborexant 5 mg, .77; 95% CI, .67-.89; P < .001; for lemborexant 10 mg, .72; 95% CI, .63-.83; P <.001).
The mean change from baseline in sleep efficiency (LSM treatment difference vs placebo for lemborexant 5 mg, 7.1%; 95% CI, 5.6-8.5%; P <.001 and for lemborexant 10 mg, 8.0%; 95% CI, 6.6-9.5%; P <.001) and wake-after-sleep onset (LSM treatment ratio vs placebo for lemborexant 5 mg, −24.0 min; 95% CI, −30.0 to −18.0 min; P <.001 and for lemborexant 10 mg, −25.4 min; 95% CI, −31.4 to −19.3 min; P <.001) 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 (LSM treatment difference vs zolpidem for lemborexant 5 mg, −6.7 min; 95% CI, −11.2 to −2.2 min; P =.004 and for lemborexant 10 mg, −8.0 min; 95% CI, −12.5 to −3.5 min; P <.001) was significantly greater for both doses of lemborexant therapy compared with zolpidem therapy measured using polysomnography.
However, 6 participants (4 in the zolpidem group and 2 in the lemborexant 5 mg group) reported serious adverse event unrelated to treatment. The other adverse events were mostly mild or moderate in severity.
The study, “Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder,” was published online in JAMA Network Open.