2024 American Academy of Neurology Abstract Website

Objective:

This post-hoc analysis of Study 304 (NCT02783729) assessed the impact of lemborexant (LEM), a competitive dual orexin receptor antagonist approved in several countries for the treatment of adults with insomnia, on morning sleepiness/alertness in subjects with varying degrees of waketime sleepiness.

Background:

Insomnia disorder is characterized by difficulty initiating and/or maintaining sleep with associated daytime impairments. Morning sleepiness increases the likelihood of daytime functional impairments such as cognitive difficulties, which can impact daily life activities. Some sleep-promoting drugs may cause residual morning sleepiness due to sedative side effects.

Design/Methods:

Study 304 was a 1-month, randomized controlled study in adults age ≥55 years with insomnia disorder (N=1006). Subjects received placebo (PBO), LEM 5mg (LEM5) or 10mg (LEM10), or zolpidem tartrate 6.25mg (not reported). A daily sleep diary assessed morning sleepiness/alertness, which was rated from 1 (extremely sleepy) to 9 (extremely alert). Parameters analyzed included change from baseline sleepiness and proportion of subjects shifting from baseline mild/moderate sleepiness (≤3) towards greater alertness (4, 5, or >5).

Results:

At baseline, 206/743 (27.7%) of subjects reported mild/moderate sleepiness (PBO, n=60; LEM5, n=68; LEM10, n=78). Change from baseline in alertness ratings increased significantly in the first 7 mornings with LEM5 and LEM10 compared with PBO (respective least squares mean treatment difference: 0.67 and 0.51). The proportion of subjects shifting from mild/moderate sleepiness towards alertness was greater with LEM5 (37%, 57%), LEM10 (41%, 55%) versus PBO (2%, 26%) across the first and last 7 mornings, respectively.

Conclusions:

More subjects who reported sleepiness at baseline reported improved morning alertness during the last week of LEM treatment versus PBO. These data align with previous findings that LEM does not affect tasks requiring morning alertness. LEM was well tolerated. This suggests that LEM is not associated with worsening morning sleepiness and may improve morning alertness.