Effect of lemborexant on sleep parameters and architecture in adult and elderly participants with mild-to-severe obstructive sleep apnea.

Objective: To evaluate sleep parameters and architecture in a post hoc analysis of participants with untreated obstructive sleep apnea (OSA) who received lemborexant (LEM) 10 mg (LEM10), a competitive dual orexin-receptor antagonist approved for the treatment of adults with insomnia.

Methods: Study E2006-A001-102 (Study 102; NCT03471871) and Study E2006-A001-113 (Study 113; NCT04647383) were multicenter, randomized, double-blind, placebo (PBO)-controlled, 2-period cross-over studies in participants with mild OSA (apnea-hypopnea index [AHI] ≥5 to <15 events/hour) and moderate (AHI ≥15 to <30 events/hour) or severe OSA (AHI ≥30 events/hour), respectively. Participants were randomized to 1 of 2 treatment sequences (Sequence A: PBO/LEM10; Sequence B: LEM10/PBO) consisting of 8 nights of treatment (LEM10 or PBO), with each treatment period separated by a ≥14-day washout period.

Perception of Lemborexant Effectiveness as Assessed by the Patient Global Impression-Insomnia Questionnaire.

Objective: Using data from a clinical study of lemborexant, evaluate responses to the Patient Global Impression-Insomnia (PGI-I) questionnaire, a simple 4-item questionnaire that assesses patients' perceptions of the effects of medication on sleep, which may help evaluate clinically meaningful changes from the patient's perspective.

Methods: Study E2006-G001-303, a 12-month, placebo (PBO)-controlled (first 6 months) Phase 3 study in adults with insomnia disorder, randomized subjects (1:1:1) to lemborexant 5 mg (LEM5; n=316), 10 mg (LEM10; n=315), or PBO (n=318). The second 6 months are not presented here.

Comment on Watson et al. Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia. . 2023, , 2493.

Health authorities and medical communities in many countries are discouraging the use of benzodiazepines and non-benzodiazepine hypnotics for patients with insomnia [...

Effect of lemborexant on sleep architecture in participants with insomnia disorder and mild obstructive sleep apnea.

Objective/background: Comorbid insomnia with obstructive sleep apnea (COMISA) is associated with worse daytime function and more medical/psychiatric comorbidities vs either condition alone. COMISA may negatively impact sleep duration and reduce rapid eye movement (REM) sleep, thereby impairing cognition. These post-hoc analyses evaluated the effect of lemborexant (LEM), a dual-orexin-receptor antagonist approved for adults with insomnia, on sleep architecture in participants with COMISA.

Effect of Lemborexant on Daytime Functioning in Adults With Insomnia: Patient-Reported Outcomes From a Phase 3 Clinical Trial.

Insomnia and some insomnia treatments can impact an individual's daytime functioning. Here, we performed post hoc analyses of patient-reported outcomes from a phase 3 clinical trial to assess the impact of lemborexant (LEM), a dual orexin receptor antagonist, on daytime functioning. Adults with insomnia were randomized 1:1:1 to receive placebo, LEM 5 mg (LEM5) or LEM 10 mg (LEM10) for 6 months.

Respiratory safety of lemborexant in adult and elderly subjects with moderate-to-severe chronic obstructive pulmonary disease.

Because some hypnotics worsen respiratory conditions, it was important to determine the respiratory safety of lemborexant, a competitive dual orexin-receptor antagonist approved to treat adults with insomnia, in subjects with moderate-to-severe chronic obstructive pulmonary disease. E2006-A001-113 (Study 113; NCT04647383) was a multicentre, multiple-dose, randomised, double-blind, placebo-controlled, two-period crossover study in adult subjects with moderate or severe chronic obstructive pulmonary disease (per spirometry-based Global Initiative for Chronic Obstructive Lung Disease [GOLD] criteria). Subjects (N = 30) were randomised to two treatment sequences comprising 8-night treatment periods (washout ≥ 14 days) with lemborexant 10 mg or placebo.

Evaluation of prescribing patterns of switching to and add-on lemborexant in patients treated with hypnotic medication: a nationwide claims database study in Japan.

Background: When considering changing hypnotic pharmacotherapy, lemborexant has attracted attention as a candidate due to its effectiveness and safety profile. However, few studies have investigated switching patterns in clinical practice.

Research Design And Methods: We conducted a retrospective cohort study using a nationwide claims database.

Efficacy and safety of insomnia treatment with lemborexant in older adults: analyses from three clinical trials.

Background: Insomnia is more common as people age. Several common hypnotics used to treat insomnia often do not adequately alleviate sleep issues in older adults and may be associated with negative residual effects such as an increased risk of falls, cognitive impairment, automobile accidents, and lack of response to auditory stimuli. The objective of these analyses of three clinical studies was to investigate the efficacy and safety of the dual orexin-receptor antagonist lemborexant (LEM) in older adults.

Re-examining the factor structure of the Insomnia Severity Index (ISI) and defining the meaningful within-individual change (MWIC) for subjects with insomnia disorder in two phase III clinical trials of the efficacy of lemborexant.

Background: The Insomnia Severity Index (ISI) is a widely used measure of insomnia severity. Various ISI research findings suggest different factor solutions and meaningful within-individual change (MWIC) to detect treatment response in patients with insomnia. This study examined an ISI factor solution and psychometric indices to define MWIC in a robust patient sample from clinical trial settings.

Efficacy of Lemborexant in Adults ≥ 65 Years of Age with Insomnia Disorder.

Background: Pharmacologic treatments are available to treat insomnia, a common and burdensome sleep disorder, but may be contraindicated in older adults who are prone to side effects from sleep-promoting drugs. These analyses of sleep diary data from Study E2006-G000-303 (Study 303) investigated the benefits of lemborexant 5 mg (LEM5) and 10 mg (LEM10) in the subgroup age ≥ 65 years with insomnia.

Method: Study 303, a 12-month, double-blind study of LEM5 and LEM10 in adults (age ≥ 18 years) with insomnia disorder (sleep onset and/or maintenance difficulties) assessed subject-reported (subjective) sleep-onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), and total sleep time (sTST).

Transitioning insomnia patients from zolpidem to lemborexant: A multicenter, open-label study evaluating a next-dose transition approach to insomnia pharmacotherapy.

Objective: Few clinical studies have assessed real-world abrupt transitioning between insomnia medications. This study assessed strategies for directly transitioning patients from zolpidem tartrate (ZOL) immediate/extended release to the dual orexin receptor antagonist, lemborexant (LEM).

Methods: This randomized, open-label, multicenter study (Study 312; E2006-A001-312) enrolled 53 adults age ≥18 years with insomnia disorder and ≥1-month history of intermittent (3-4 nights/week) or frequent (≥5 nights/week) ZOL use.

A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea.

Study Objectives: To evaluate the respiratory safety of lemborexant among adults and older adults with moderate to severe obstructive sleep apnea (OSA).

Methods: E2006-A001-113 (Study 113; NCT04647383) was a double-blind, two-period crossover, placebo-controlled study in adults (ages ≥ 45 to ≤ 90 years, n = 33) with moderate (apnea-hypopnea index [AHI] score ≥ 15 to < 30 events/h, n = 13) or severe (AHI ≥ 30 events/h, n = 20) OSA. Participants were randomized to lemborexant 10 mg (LEM10) or placebo (PBO) for two treatment periods of 8 nights with a ≥ 14-day washout period.

Efficacy and safety of lemborexant in subjects previously treated with placebo for 6 months in a randomized phase 3 study.

Objective/background: To examine the effects of lemborexant (LEM) 5 mg (LEM5) or LEM 10 mg (LEM10) following extended placebo treatment. This post-hoc analysis used subject-reported sleep outcomes data from a phase 3 trial.

Patients/methods: The subjects in these post-hoc analyses were randomized to placebo for 6 months (Time Period [TP]1) in Study E2006-G000-303 (SUNRISE-2; NCT02952820).

Lemborexant levels in breast milk after single doses in healthy, lactating women.

Aims: The aim of this study is to determine the cumulative amount of lemborexant (a competitive dual orexin receptor antagonist approved to treat adults with insomnia) excreted in human breast milk and the relative infant dose (RID) as a proportion of daily maternal dose.

Methods: E2006-A001-010 was a single-centre, open-label study that enrolled lactating women (≥18 years) who breastfed for ≥5 weeks postpartum. After overnight fasting, subjects received a single 10-mg oral dose of lemborexant.

Efficacy and safety of lemborexant in midlife women with insomnia disorder.

Objective: Insomnia is common in midlife women. The efficacy and safety of lemborexant (LEM), a competitive dual orexin receptor antagonist, was assessed for 12 months in a subgroup of midlife women (age, 40-58 y) from Study E2006-G000-303 (Study 303; SUNRISE-2).

Methods: This was a randomized, double-blind, placebo (PBO)-controlled (first 6 mo) study of adults with insomnia disorder ( N = 949).

The abuse potential of lemborexant, a dual orexin receptor antagonist, according to the 8 factors of the Controlled Substances Act.

Rationale: Lemborexant (LEM) is a dual orexin receptor antagonist (DORA) approved in multiple countries including the USA, Japan, Canada, Australia, and several Asian countries for the treatment of insomnia in adults. As a compound with central nervous system activity, it is important to understand the abuse potential of LEM with respect to public health.

Objectives: This review discusses data for LEM relevant to each of the 8 factors of the United States Controlled Substances Act.

Effect of discontinuation of lemborexant following long-term treatment of insomnia disorder: Secondary analysis of a randomized clinical trial.

Discontinuing long-term pharmacotherapy for insomnia can result in rebound insomnia or withdrawal symptoms and suboptimal treatment. Post hoc analyses evaluated rebound insomnia and withdrawal symptoms among the subset of subjects from a phase III, 12-month, global, multicenter, randomized, double-blind, parallel-group study who completed 12 or 6 months of active treatment and follow-up period. Study E2006-G000-303 (Study 303) included adults (N = 655) with subjective sleep-onset latency ≥30 min and/or subjective wake-after-sleep onset ≥60 min at least three times weekly during the 4 weeks before enrollment.

Exposure-Response Analyses of Polysomnography and Subjective Sleep Efficacy End Points From the Phase 3 Trials of Lemborexant, a Dual Orexin Receptor Antagonist for the Treatment of Insomnia.

This report describes polysomnography and sleep diary exposure-response analyses from Study E2006-G000-304 (Study 304), a 1-month trial of 5- or 10-mg lemborexant, zolpidem, or placebo; and Study E2006-G000-303 (Study 303), a 6-month trial of 5- or 10-mg lemborexant or placebo. Studies 304 and 303 included 1006 (86%) and 956 (68%) (female) participants, respectively; >40% were ≥65 years, with individual lemborexant exposures derived from a previously described pharmacokinetic model. Linear mixed-effects analyses of polysomnography: latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) quantified the change from baseline given lemborexant exposure, time, and covariates, guided by consensus recommendations regarding clinical significance.

Comparison of the treatment effectiveness between lemborexant and zolpidem tartrate extended-release for insomnia disorder subtypes defined based on polysomnographic findings.

Study Objectives: Patients with chronic insomnia may respond differently to therapeutic modalities. This study examined differences in response of individuals with 2 insomnia phenotypes-short sleep duration (I-SSD; < 6 hours) and normal sleep duration (I-NSD; ≥ 6 hours) determined by polysomnography-to treatment with lemborexant and zolpidem tartrate extended-release 6.25 mg (zolpidem ER), compared with placebo.

Abuse Potential of Lemborexant, a Dual Orexin Receptor Antagonist, Compared With Zolpidem and Suvorexant in Recreational Sedative Users.

Background: Lemborexant (LEM) is a dual orexin receptor antagonist approved for the treatment of insomnia in adults in multiple countries including the the United States, Japan, Canada, Australia and several Asian countries.

Procedures: This was a randomized, single-dose, single-center, double-blind, active-control, 6-way crossover study to evaluate LEM abuse potential. The study assessed oral doses of LEM 10 mg (LEM10), 20 mg (LEM20), and 30 mg (LEM30) compared with placebo (PBO), zolpidem (ZOL) immediate release 30 mg, and suvorexant (SUV) 40 mg.