Effect of Lemborexant on Sleep Onset and Maintenance in Patients with Comorbid Insomnia Disorder and Mild Obstructive Sleep Apnea (P4-13.001)

Abstract

<h3>Objective:</h3> Evaluate the effects of lemborexant (LEM), a competitive dual orexin receptor antagonist approved in multiple countries for the treatment of insomnia disorder, in patients with comorbid insomnia and obstructive sleep apnea (COMISA) of mild severity. <h3>Background:</h3> Insomnia and obstructive sleep apnea (OSA) are frequent comorbid sleep disorders. However, commonly prescribed hypnotic drugs may exacerbate pre-existing respiratory dysfunction. <h3>Design/Methods:</h3> Study E2006-G000-304 (Study 304; NCT02783729) was a 1-month, randomized, double-blind, placebo (PBO)-controlled and active-comparator (zolpidem tartrate extended release 6.25mg [ZOL]) study of LEM 5mg (LEM5) and LEM 10mg (LEM10). This post-hoc analysis included subjects age ≥55y with both insomnia disorder and mild OSA (apnea hypopnea index [AHI] ≥5 and &lt;15 events/h of sleep). Sleep onset (latency to persistent sleep [LPS]), sleep efficiency (SE = total sleep time/time in bed), wake after sleep onset (WASO), and WASO in the second half of the night (WASO2H) were assessed at Nights 1/2 (NT1/2) and Nights 29/30 (NT29/30) using polysomnography. <h3>Results:</h3> 40.8% of the population (n=410/1006) had mild OSA, with AHI (mean [SD]) at screening of 9.33 (2.9) events/h; median age 65y, and 83.9% were female. Changes from baseline in SE were larger (increased, indicating improvement) and significantly different for both LEM5 and LEM10 versus PBO and ZOL (P&lt;0.05) on NT1/2 and NT29/30. Compared with PBO, changes from baseline in LPS, WASO, and WASO2H were all larger (decreased, indicating improvement) and significantly different (P&lt;0.005) with LEM5 and LEM10 at both time points. Compared with ZOL, LEM10 produced significantly greater decreases from baseline for LPS, WASO, and WASO2H at NT1/2 and NT29/30 (P&lt;0.01, all assessments); and LEM5 on NT29/30 (P&lt;0.02, all assessments). LEM was well tolerated and consistent with its known safety profile. <h3>Conclusions:</h3> These results demonstrate the effectiveness of LEM versus PBO and ZOL in an older patient population with untreated COMISA of mild severity. <b>Disclosure:</b> Margaret Moline has received personal compensation for serving as an employee of EISAI, INC.. Margaret Moline has received intellectual property interests from a discovery or technology relating to health care. Margaret Moline has received personal compensation in the range of $0-$499 for serving as a review, loan repayment program with NIH. Dr. Cheng has received personal compensation for serving as an employee of Eisai Inc. Dinesh Kumar has received personal compensation for serving as an employee of Eisai. Dr. Ramos has received personal compensation for serving as an employee of Eisai. Dr. Lowe has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai . Dr. Lowe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz. Dr. Lowe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Paladin . Dr. Lowe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sunovion . Dr. Lowe has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Eisai . Dr. Lowe has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sunovion . The institution of Dr. Lowe has received research support from Axsome Therapeutics . The institution of Dr. Lowe has received research support from Boehringer Ingelheim .