Insomnia disorder, characterized by difficulty initiating and/or maintaining sleep 3 nights or more per week for 3 months or longer, is prevalent and associated with health risks in older adults.¹ Cognitive behavior therapy for insomnia is a first-line insomnia therapy and has been shown to improve sleep in older patients with insomnia.^2,3 However, pharmacologic treatment may be necessary in cases in which cognitive behavior therapy for insomnia is not effective or not accessible to the patient.^2,4 Benzodiazepines and other sedative-hypnotic medications are prescribed frequently to treat insomnia in older adults, although many treatment options do not adequately address both sleep initiation and maintenance symptoms.^5,6 This inadequacy is particularly problematic because older individuals tend to have relatively more difficulty maintaining sleep.⁷ Adverse effects from these medications may be associated with falls, hip fractures, and risk of unintentional injury.^8,9 Thus, the American Academy of Sleep Medicine¹⁰ and the American Geriatric Society¹¹ recommend restricting or foregoing use of sedative-hypnotic drugs in older adults.

Study Objectives: To assess long-term efficacy and safety of lemborexant (LEM), a novel dual orexin receptor antagonist, versus placebo in adults with insomnia disorder. Methods: This was a 12-month, global, multicenter, randomized, double-blind, parallel-group phase 3 study comprising a 6-month placebo-controlled period (reported here) followed by a 6-month active-treatment-only period (reported separately). A total of 949 participants with insomnia (age ≥18 years) were randomized, received treatment with an oral dose of placebo or LEM (5 mg [LEM5] or 10 mg [LEM10]) and were analyzed. Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored throughout the study. Results: Decreases from baseline in patient-reported (subjective) sleep onset latency and subjective wake after sleep onset, and increases from baseline in subjective sleep efficiency, were significantly greater with LEM5 and LEM10 versus placebo. Significant benefits over placebo were observed at the end of month 6, and at most time points assessed over the 6-month period, indicating long-term sustained efficacy of LEM. A significantly greater percentage of sleep onset responders and sleep maintenance responders were observed with LEM treatment versus placebo. Participants treated with LEM reported a significant improvement in quality of sleep after 6 months versus placebo. The majority of TEAEs were mild or moderate. There was a low rate of serious TEAEs and no deaths. Conclusions: LEM5 and LEM10 provided significant benefit on sleep onset and sleep maintenance in individuals with insomnia disorder versus placebo, and was well tolerated. Clinical trial registration: ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39

Lemborexant is a dual orexin receptor antagonist approved in the United States, Japan, and Canada for the treatment of insomnia in adults. We report effectiveness and safety outcomes in subjects with insomnia who received up to twelve months of continuous lemborexant treatment in Study E2006-G000-303 (Study 303; SUNRISE-2). Study 303 was a twelve-month, global, multicenter, randomized, double-blind, parallel-group, Phase 3 study divided into two treatment periods. In Treatment Period 1 (first six months), subjects (n = 949, Full Analysis Set) were randomized to daily placebo, lemborexant 5 mg (LEM5) or lemborexant 10 mg (LEM10). In Treatment Period 2 (second six months), placebo subjects were rerandomized to LEM5 or LEM10, and subjects randomized to lemborexant continued their assigned treatment (LEM5, n = 251; LEM10, n = 226). Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored. For all sleep parameters, the significant benefits observed with LEM5 and LEM10 versus placebo over six months were maintained at twelve months in subjects who received twelve continuous months of treatment. There was no evidence of rebound insomnia or withdrawal in either lemborexant group following treatment discontinuation. Over twelve months of lemborexant treatment, most TEAEs were mild/moderate; the most common TEAEs were nasopharyngitis, somnolence and headache. LEM5 and LEM10 had significant benefit on sleep onset and sleep maintenance compared with placebo, and importantly, lemborexant effectiveness persisted at twelve months, suggesting that lemborexant may provide long-term benefits for subjects with insomnia. ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.

Donepezil 23 mg/d, recently approved in the United States for treatment of moderate to severe Alzheimer's disease (AD), was developed to address the need for an additional treatment option for patients with advanced AD. This report, based on a pivotal phase 3 study, presents a detailed analysis of the safety and tolerability of increasing donepezil to 23 mg/d compared with continuing 10 mg/d.

Study Objectives:To evaluate the effect of lemborexant versus zolpidem tartrate extended release 6.25 mg (ZOL) or placebo (PBO) on postural stability, auditory awakening threshold (AAT), and cognit...

Residual next-day effects of sleep-promoting drugs are common and an important safety issue. Lemborexant is a dual orexin receptor antagonist approved in the United States and Japan for treatment o...