EFFICACY OF LEMBOREXANT COMPARED WITH ZOLPIDEM EXTENDED RELEASE AND PLACEBO IN ELDERLY SUBJECTS WITH INSOMNIA: RESULTS FROM A PHASE 3 STUDY (SUNRISE 1)

Abstract

Introduction Difficulties initiating sleep and maintaining sleep throughout the night are reported by more than 50% of elderly individuals. Many treatments for insomnia are not indicated for the treatment of sleep maintenance insomnia, which can be an issue particularly for elderly individuals whose primary complaints tend to be sleep maintenance insomnia. Here we report results from the subgroup of elderly subjects (65+ years) enrolled in a Phase 3 study of the dual orexin receptor antagonist lemborexant. The study enrolled older individuals (55+ years) with sleep maintenance insomnia, in which the efficacy of lemborexant, measured by polysomnography (PSG), was compared with both placebo (PBO) and zolpidem tartrate extended release (ZOL), the formulation of zolpidem that has been approved to treat sleep maintenance problems. Methods SUNRISE 1 was a randomized, double-blind, placebo- and active-controlled, 1-month, global Phase 3 study. The overall study enrolled female subjects age 55 and older and males age 65 and older. Results of the current analysis include only those age 65 and older. Subjects met DSM-5 criteria for insomnia disorder, and had a primary complaint of sleep maintenance insomnia. Current insomnia symptoms were confirmed with both a sleep diary and PSG. Subjects with symptoms of other sleep disorders (e.g., moderate to severe sleep apnea, periodic limb movement disorder, restless legs syndrome) were excluded, but those with sufficiently-treated comorbid medical or psychiatric conditions could be included. After an approximately 2-week single-blind Run-in Period where all subjects received placebo (PBO), subjects were randomized to PBO, ZOL (6.25mg), or lemborexant (LEM; 5mg [LEM5] or 10mg [LEM10]) for 1 month. Study drug was taken within 5 min of the start of the sleep period, which was calculated based on the mean habitual bedtime from the sleep diary. Average values from paired PSGs from each subject at Baseline (during the placebo run-in), Nights 1/2, and Nights 29/30 were analyzed for latency to persistent sleep (LPS), wake after sleep onset (WASO), WASO in the second half of the night (WASO2H), and sleep efficiency (SE). SE is defined as total sleep time divided by the time in bed, which was standardized for all subjects at 8 hours. Results A total of 1006 were randomized into the study. Of these, 453 (45%) were 65 years or older (137 males, 316 females) and are included in the results presented below. Most subjects (433/453; 95.6%) completed the study. A total of 8 (1.8%) subjects discontinued due to an adverse event. Table 1 shows difference from placebo in change from baseline values for PSG variables by timepoint (Nights 1/2, Nights 29/30). All comparisons of LEM5 and LEM10 to both PBO and ZOL were statistically significant at p The most common AEs in elderly subjects (>2% of elderly subjects in any active treatment group and >PBO) were headache, with rates of 4.3% (PBO), 4.2% (ZOL), 5% (LEM5), and 5% (LEM10), and somnolence, with rates of 2.2% (PBO), 0.8% (ZOL), 3.4% (LEM5), and 7.4% (LEM10). Conclusions Lemborexant improved both sleep onset and sleep maintenance compared to both PBO and ZOL. Importantly, LEM was significantly better than ZOL at reducing the amount of time spent awake during the second half of the night, which is the time when elderly individuals have the most difficulty maintaining sleep. These subpopulation analyses are similar to the results from the overall study, which included older adults 55-64 years as well. In this study, lemborexant appeared to be well-tolerated. Results of this study support the efficacy and safety of lemborexant as a treatment for insomnia disorder in elderly individuals who suffer from sleep maintenance insomnia. This research was funded by Eisai Inc. and Purdue Pharma L.P.