48. TRANSITIONING BETWEEN DRUG CLASSES IN ELDERLY ADULTS: DATA FROM TWO STUDIES WITH LEMBOREXANT AND Z-DRUGS

Introduction

Insomnia is one of the most prevalent sleep disorders in older adults. Switching insomnia medications occurs frequently in clinical practice for a variety of reasons, including clinical response, side effects, cost, and patient preference. Few studies have evaluated the impact of transitioning between insomnia medications, especially in the elderly population for whom insomnia is disproportionally prevalent. Lemborexant (LEM) is a dual orexin receptor-antagonist approved in multiple countries, including the United States and Japan, for the treatment of adults with insomnia. Two studies (United States: E2006-A001-312, Study 312, NCT04009577; Japan: E2006-M081-401, Study 401, NCT04742699) evaluated the strategies for transitioning to LEM 5 mg (LEM5) or 10 mg (LEM10) in adults with insomnia who were dissatisfied with the efficacy and/or tolerability of their current treatment with a non-benzodiazepine sedative-hypnotic (Z-drug). This post hoc analysis evaluated the success rate of transitioning to LEM and the impact on insomnia severity in participants aged ≥65 years.

Methods

Both open-label studies examined prespecified dosing paradigms for participants directly transitioning from a Z-drug to LEM without down-titration of the Z drug. Study 312 consisted of a 3-week Screening Period (participants continued zolpidem tartrate [ZOL]), a 2-week Titration Period (TITR), a 12-week Extension Period (EXT; not reported here), and a 4-week Follow-up Period (not reported here). In Study 312, adults with insomnia who used ZOL intermittently (3–4 nights/week) or frequently (≥5 nights/week) were assigned to 1 of 2 cohort s. Cohort 1, intermittent ZOL users and participants with 1 week each of intermittent and frequent ZOL usage, began TITR with LEM 5. Cohort 2 consisted of frequent ZOL users who received ZOL ≥5 nights/week during the last 2 weeks of the screening period and were randomized 1:1 to LEM5 (Cohort 2A) or LEM10 (Cohort 2 B). Study 401 followed a similar design except for a 2-week Screening Period where participants continued their current Z-drug (ZOL, zopiclone, or eszopiclone). All participants in Study 401 started with LEM 5. Endpoints in this post hoc analysis included the proportion of participants who successfully transitioned to LEM at the end of TITR and change from baseline in insomnia severity (assessed by the Insomnia Severity Index [ISI]). Successful transition was defined as the proportion of participants who elected to remain on LEM in the EXT. Safety information was also collected.

Results

Of the 53 participants in the Full Analysis Set in Study 31 2, 21 participants were aged ≥65 years (Cohort 1, n=5; Cohort 2A, n=5; Cohort 2B, n=11). In Cohort 1, 4 of 5 (80.0%) participants successfully transitioned from ZOL to LEM. In Cohort 2A, 5 of 5 (100.0%) successfully transitioned, and in Cohort 2B, 7 of 11 (63.6%) successfully transitioned from ZOL to LEM. Overall mean ISI scores in study 312 decreased (improved) from baseline to the end of TITR (mean [SD] improvement of −4.0 [7.3]); decreases in mean ISI scores were observed in each cohort following transition from ZOL to LEM. Of the 25 participants in the Full Analysis Set in Study 401 in the Z-drug group, 6 participants were aged ≥65 years. The proportion of participants with successful LEM treatment in the Z-drug group was 100.0 % (n=6). Mean ISI scores in study 401 decreased from baseline to the end of TITR in the Z-drug group (mean [SD] improvement of −0.7 [6.5]). No new safety signals emerged when transitioning to LEM treatment in this population of older adults.

Conclusions

These data indicate that adults aged ≥65 years can successfully transition directly from a Z-drug to LEM. LEM was well tolerated, and no new safety signals emerged in this subset of elderly participants.