Lemborexant for treating sleep issues

Abstract

To provide a method for improving subjective sleep efficiency of a subject, a method for reducing subjective sleep latency, and / or a method for reducing subjective nocturnal awakening.SOLUTION: Disclosed herein is a method for improving subjective sleep efficiency of a subject, reducing subjective sleep latency, and / or reducing subjective nocturnal awakening, the method comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent amount of a pharmaceutically acceptable salt thereof. Also disclosed herein is lemborexant or a pharmaceutically acceptable salt thereof for use in improving subjective sleep efficiency of a subject, reducing subjective sleep latency, and / or reducing subjective nocturnal awakening, the use comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent amount of a pharmaceutically acceptable salt thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] Disclosed herein are novel methods and uses of lemborexant for improving sleep parameters such as subjective sleep efficiency, decreasing subjective sleep onset latency, and / or decreasing subjective sleep-related awakenings. [Background technology]

[0002] Sleep disorders such as insomnia are characterized by difficulty falling asleep, staying asleep, or early morning awakening, accompanied by complaints of daytime dysfunction. Currently available pharmacological treatments include benzodiazepines, non-benzodiazepine gamma-aminobutyric acid receptor agonists, the recently approved dual orexin receptor antagonist (DORA) suvorexant, sedative antidepressants, melatonin and melatonin agonists, antihistamines, and other prescription and nonprescription medications with sedative properties.

[0003] The orexin neuropeptides (orexin A and orexin B) are recognized as critical upstream regulators of many wake-promoting neurotransmitters via two G protein-coupled receptors, the orexin 1 receptor and the orexin 2 receptor. Recently, antagonism of orexin receptors, particularly both orexin receptors, with small molecules has emerged as an alternative approach to treating sleep problems. There remains an unmet medical need for conveniently administered, safe, and effective therapies to address insomnia.

[0004] Lemborexant, also known as E2006, is a dual orexin receptor antagonist that has been studied in clinical trials and shown to have beneficial properties, such as reducing sleep-onset awakenings, reducing sleep onset latency, and / or improving sleep efficiency. Summary of the Invention [Means for solving the problem]

[0005] In some embodiments, disclosed herein is a method for reducing subjective sleep onset latency (sSOL) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein sSOL is reduced relative to baseline for at least one month.

[0006] In some embodiments, disclosed herein is a method of improving subjective sleep efficiency (sSE) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein sSE is increased relative to baseline for at least one month.

[0007] In some embodiments, disclosed herein is a method of reducing subjective wakefulness after sleep onset (sWASO) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein sWASO is reduced relative to baseline for at least one month.

[0008] In some embodiments, disclosed herein are methods for identifying a subject responsive to treatment with lemborexant or a pharmaceutically acceptable salt thereof, comprising: (a) determining the subject's pre-treatment period subjective wake after onset (sWASO); (b) if the pre-treatment period sWASO is 60 minutes or greater, administering 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, to the subject for a treatment period; (c) determining the subject's post-treatment period sWASO; and (d) if the post-treatment period sWASO is less than 60 minutes and the post-treatment period sWASO is 10 minutes or more shorter than the pre-treatment period sWASO, administering 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, to the subject.

[0009] In some embodiments, disclosed herein are methods for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving a sustained reduction in time to fall asleep as measured by subjective sleep onset latency (sSOL) compared to placebo over at least one month of treatment.

[0010] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving a sustained reduction in time to fall asleep as measured by subjective sleep onset latency (sSOL) compared to placebo through 6 months of treatment.

[0011] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for at least one month, and wherein the dosage form is capable of maintaining a reduction in time to fall asleep as measured by subjective sleep onset latency (sSOL) compared to placebo throughout at least one month of treatment.

[0012] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for six months, and wherein the dosage form is achievable in terms of maintaining a reduction in time to fall asleep as measured by subjective sleep onset latency (sSOL) compared to placebo throughout the six months of treatment.

[0013] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvements in sleep efficiency as measured by subjective sleep efficiency (sSE) compared to placebo over at least one month of treatment.

[0014] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvements in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo through 6 months of treatment.

[0015] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for at least one month, and wherein the dosage form is capable of maintaining improvements in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo over at least one month of treatment.

[0016] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for six months, and wherein the dosage form is capable of maintaining improvements in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo throughout the six months of treatment.

[0017] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvement in wake after sleep onset (sWASO) compared to placebo over at least one month of treatment.

[0018] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvement in wake after sleep onset (sWASO) compared to placebo through 6 months of treatment.

[0019] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for at least one month, and wherein the dosage form is capable of maintaining an improvement in sleep-wake after sleep onset (sWASO) compared to placebo over at least one month of treatment.

[0020] In some embodiments, disclosed herein is a method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for six months, and wherein the dosage form is capable of achieving sustained improvement in wake after sleep onset (sWASO) compared to placebo throughout six months of treatment.

[0021] In some embodiments, disclosed herein is a method of treating insomnia in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep onset latency is reduced relative to baseline for at least one month.

[0022] In some embodiments, disclosed herein is a method of treating insomnia in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep efficiency is increased relative to baseline for at least one month.

[0023] In some embodiments, disclosed herein is a method of treating insomnia in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective awakenings after sleep are reduced relative to baseline for at least one month.

[0024] In some embodiments, disclosed herein are methods for treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, the method comprising orally administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night and within minutes of going to bed, with at least 7 hours remaining until the intended wake-up time; if the 5 mg dose is well tolerated but ineffective, the dose may then be increased to 10 mg once daily; and the dosage form is achievable in terms of maintaining a reduction in time to sleep onset in subjective sleep onset latency (sSOL), wherein the sSOL is reduced by at least 15 minutes relative to baseline, over at least one month of treatment.

[0025] In some embodiments, disclosed herein are methods for treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, the method comprising orally administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night immediately prior to going to bed with at least 7 hours remaining until the intended wake-up time, the daily dose may be increased to 10 mg based on clinical response and tolerability, and the dosage form is achievable in terms of maintaining a reduction in time to sleep onset in subjective sleep onset latency (sSOL), wherein the sSOL is reduced by at least 15 minutes relative to baseline, over at least one month of treatment.

[0026] In some embodiments, disclosed herein are methods for treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, the method comprising orally administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night and within minutes of going to bed, with at least 7 hours remaining until the intended wake-up time, wherein if the 5 mg dose is well tolerated but not effective, the dose may be subsequently increased to 10 mg once daily, and the dosage form is achievable in maintaining improvements in sleep efficiency in subjective sleep efficiency (sSE) over at least one month of treatment, wherein sSE is improved by at least 4% over baseline.

[0027] In some embodiments, disclosed herein are methods for treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, the method comprising orally administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night immediately prior to going to bed with at least 7 hours remaining until the intended wake-up time, the daily dose may be increased to 10 mg based on clinical response and tolerability, and the dosage form is achievable in maintaining improvements in sleep efficiency in subjective sleep efficiency (sSE) over at least one month of treatment, wherein sSE is improved by at least 4% over baseline.

[0028] In some embodiments, disclosed herein are methods for treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, the method comprising orally administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night and within minutes of going to bed, with at least 7 hours remaining until the intended wake-up time; if the 5 mg dose is well tolerated but not effective, the dose may then be increased to 10 mg once daily; and the dosage form is achievable in terms of maintaining an improvement in subjective wake-after-sleep syndrome (sWASO) over at least one month of treatment, with sWASO decreasing by at least 29 minutes relative to baseline.

[0029] In some embodiments, disclosed herein are methods for treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, the method comprising orally administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night immediately prior to going to bed with at least 7 hours remaining until the intended wake-up time, the daily dose may be increased to 10 mg based on clinical response and tolerability, and the dosage form is achievable in terms of maintaining an improvement in subjective wakefulness after sleep onset (sWASO) over at least one month of treatment, wherein sWASO is reduced by at least 29 minutes compared to baseline.

[0030] In some embodiments, disclosed herein is a method for treating insomnia characterized by difficulty falling asleep and / or staying asleep, with or without accompanying impairment in daily functioning, comprising administering to a subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof.

[0031] In some embodiments, administration of lemborexant or a pharmaceutically acceptable salt thereof does not significantly affect postural stability in a subject relative to placebo. [Brief explanation of the drawings]

[0032] [Figure 1] Changes from baseline in median, first and third quartiles of subjective sleep onset latency for patients treated with placebo, 5 mg lemborexant, or 10 mg lemborexant are shown as a function of treatment duration. [Figure 2] The first and third quartile median times for subjective sleep onset latency for patients treated with placebo, 5 mg lemborexant, or 10 mg lemborexant are shown as a function of treatment duration. [Figure 3] Figure 1 shows the change from baseline (least squares means) in percentage sleep efficiency for subjective sleep efficiency in patients treated with placebo, 5 mg lemborexant, or 10 mg lemborexant as a function of treatment duration. [Figure 4] Figure 1 shows the mean percentage sleep efficiency as a function of treatment duration for subjective sleep efficiency in patients treated with placebo, 5 mg lemborexant, or 10 mg lemborexant. [Figure 5] The least squares mean change from baseline in median time to subjective awakening after sleep onset for patients treated with placebo, 5 mg lemborexant, or 10 mg lemborexant is shown as a function of treatment duration. [Figure 6]Mean time to subjective awakening after sleep onset as a function of treatment duration for patients treated with placebo, 5 mg lemborexant, or 10 mg lemborexant. [Figure 7] Changes from baseline in median time, first and third quartiles of latency to persistent sleep for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant are shown as a function of treatment duration. [Figure 8] 1 shows model estimates of change from baseline in percentage sleep efficiency for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant as a function of treatment duration. [Figure 9] Model estimates of change from baseline in wake after sleep onset for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant are shown as a function of treatment duration. [Figure 10] Model estimates of change from baseline in wake after sleep onset in the second half of the night for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant are shown as a function of treatment duration. [Figure 11A] Changes from baseline (least squares means) in four domains of the Cognitive Performance Assessment Battery at Days 2 / 3 and 30 / 31 for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant are shown. [Figure 11B] Changes from baseline (least squares means) in four domains of the Cognitive Performance Assessment Battery at Days 2 / 3 and 30 / 31 for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant are shown. [Figure 11C] Changes from baseline (least squares means) in four domains of the Cognitive Performance Assessment Battery at Days 2 / 3 and 30 / 31 for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant are shown. [Figure 11D] Changes from baseline (least squares means) in four domains of the Cognitive Performance Assessment Battery at Days 2 / 3 and 30 / 31 for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant are shown. [Figure 12] Changes from baseline in minutes of prolonged wakefulness duration (defined as periods of wakefulness lasting 5 minutes or more while trying to sleep) on Days 2 / 3 and 30 / 31 for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant are shown (least squares means). [Figure 13A] Shown are the least squares means changes from baseline in minutes asleep during Stage N1, Stage N2, and Stage N3 sleep on nights 1 / 2 and 29 / 30, respectively, for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant. [Figure 13B] Shown are the least squares means changes from baseline in minutes asleep during Stage N1, Stage N2, and Stage N3 sleep on nights 1 / 2 and 29 / 30, respectively, for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant. [Figure 13C] Shown are the least squares means changes from baseline in minutes asleep during Stage N1, Stage N2, and Stage N3 sleep on nights 1 / 2 and 29 / 30, respectively, for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant. [Figure 14] Shown are the least squares means changes from baseline in minutes asleep during non-rapid eye movement (NREM) sleep on nights 1 / 2 and 29 / 30 for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant. [Figure 15]Shown are least squares means changes from baseline in minutes spent asleep during non-REM sleep on nights 1 / 2 and 29 / 30 for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant. [Figure 16] Shown are the mean changes from baseline in minutes of REM latency on nights 1 / 2 and 29 / 30 for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant. DETAILED DESCRIPTION OF THE INVENTION

[0033] As used herein, the following definitions shall apply unless otherwise indicated.

[0034] As used herein, the term "a" refers to one or more.

[0035] As used herein, the term "lemborexant" means a compound having the structure: [ka] which is also known as (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide or (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide.

[0036] As used herein, the term "therapeutically effective amount" means an amount sufficient to produce an intended result, including, but not limited to, a decrease in subjective sleep onset latency, an improvement in subjective sleep efficiency, a decrease in subjective awakenings during the night, or an improvement in insomnia. The present disclosure involves administering to a subject a therapeutically effective amount of lemborexant or a pharmaceutically acceptable salt thereof. In some embodiments, the therapeutically effective amount is 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof. In some embodiments, the therapeutically effective amount is 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof.

[0037] As used herein, the term "pharmaceutically acceptable salt" refers to a salt that retains the desired biological activity of the parent compound and does not impart undesired toxicological effects. Examples of such salts include, but are not limited to, (a) acid addition salts formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, and nitric acid; and salts formed with organic acids, such as acetic acid, oxalic acid, tartaric acid, succinic acid, maleic acid, fumaric acid, gluconic acid, citric acid, malic acid, ascorbic acid, benzoic acid, tannic acid, palmitic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonic acid, and polygalacturonic acid; and (b) salts formed from elemental anions, such as chlorine, bromine, and iodine. See, for example, Haynes, et al., J. Pharm. Sci., 2005, 94, 10; and Berge, et al., J. Pharm. Sci., 1977, 66, 1, which are incorporated herein by reference.

[0038] In some embodiments, lemborexant or a pharmaceutically acceptable salt thereof is administered in the form of a composition. The composition may be in any suitable dosage form. In some embodiments, lemborexant or a pharmaceutically acceptable salt thereof is in a solid dosage form, such as, for example, a capsule, granules, lozenges, pellets, pills, powders, suspensions, and tablets.

[0039] In some embodiments, the composition further comprises at least one additional pharmaceutically acceptable component, which in some embodiments is selected from a pharmaceutically acceptable carrier, a pharmaceutically acceptable vehicle, and a pharmaceutically acceptable excipient.

[0040] As used herein, the term "pharmaceutically acceptable" means the carrier, diluent, excipient or vehicle is compatible with the other ingredients of the composition and non-toxic to the subject.

[0041] As used herein, the term "pharmaceutically acceptable excipient" refers to an inactive ingredient used as a vehicle (e.g., water, capsule shell, etc.), diluent, or component to constitute a dosage form or pharmaceutical composition containing a drug, such as a therapeutic agent. The term also encompasses inactive ingredients that impart cohesive (e.g., binder), disintegrant (e.g., disintegrant), lubricant (e.g., lubricant), and / or other functions (e.g., solvent, surfactant, etc.) to the composition.

[0042] As used herein, the term "subject" refers to an animal subject, such as a mammalian subject, e.g., a human. As used herein, a subject can be of any age. In some embodiments, a subject can be 18 years of age or older. In some embodiments, a subject can be 55 years of age or older.

[0043] As used herein, the terms "treatment" and "treating" refer to an approach for obtaining beneficial or desired results, including but not limited to, a therapeutic benefit and / or a prophylactic benefit.

[0044] As used herein, the term "subjective sleep onset latency" is abbreviated as "sSOL" and refers to an estimate of the number of minutes it takes a subject to fall asleep from the time they attempt to fall asleep to the time they fall asleep. In some embodiments, sSOL is derived from data entered in a subject's sleep diary.

[0045] As used herein, the term "subjective wakefulness onset" is abbreviated as "sWASO" and refers to the total estimated number of minutes of wakefulness during the night after the initial sleep onset, which is operationalized as the time when the subject gets out of bed that day, until the time when the subject stops trying to sleep that night. In some embodiments, sWASO is derived from data recorded in the subject's sleep diary. As used herein, "improvement of sWASO" refers to a reduction in sWASO.

[0046] As used herein, the term "subjective total sleep time" is abbreviated as "sTST" and refers to the derived number of minutes of sleep from the onset of sleep to the point at which the subject stops trying to sleep that night. In some embodiments, sTST is derived from data entered into the subject's sleep diary.

[0047] As used herein, the term "subjective sleep efficiency," abbreviated as "sSE," refers to the ratio of sTST per subjective time in bed, calculated as the interval from when a subject reports trying to sleep to when the subject stops trying to sleep that night (operationalized as when the subject gets out of bed that day), and the time spent asleep, calculated by subtracting sWASO from subjective time in bed. As used herein, "improving sleep efficiency in subjective sleep efficiency (sSE)" refers to an increase in sleep efficiency in subjective sleep efficiency (sSE).

[0048] The subjective determination of the aforementioned sleep parameters is known in the art. In some embodiments, the sleep parameters are determined by subjective measurement, such as, for example, interviewing the subject, keeping a sleep diary, or assessing how restful and restful sleep was using a standardized questionnaire (e.g., the Pittsburgh Sleep Quality Index (Buysse et al., Psychiatry Research (1989), 28(2), 193-213)).

[0049] In some embodiments, a sleep diary was used to assess subject-reported sleep parameters (i.e., subjective assessments), including subjective sleep onset latency (sSOL), subjective sleep efficiency (sSE), subjective WASO (sWASO), and subjective total sleep time (sTST). Subjects were instructed to complete a sleep diary developed based on the consensus sleep diary as described in Carney et al., "The consensus sleep diary: standardizing prospective sleep self-monitoring," Sleep 2012;35(2):287-302. In some embodiments, a sleep diary was used to assess the subject's overall perception of the quality of their sleep from the previous night by asking the following question: "How would you rate the quality of your sleep last night?" Subjects rated their sleep quality on a 1-9 scale, with 1 representing very poor sleep and 9 representing very good sleep. In some embodiments, a sleep diary was used to assess subjective morning sleepiness by asking the following question: "How awake / sleepy are you this morning?" Subjects rated their level of sleepiness / alertness on a 1-9 Likert scale, with 1 being very sleepy and 9 being very awake.

[0050] As used herein, the term "insomnia severity index," abbreviated as "ISI," is an index calculated using a seven-item self-report questionnaire that assesses the nature, severity, and impact of insomnia (see Bastien, CH, et al. "Validation of the Insomnia Severity Index as an outcome measure for insomnia research." Sleep Med. 2001;2(4):297-307). This questionnaire assesses (1) the severity of sleep onset; (2) sleep maintenance; (3) early morning awakening problems; (4) sleep dissatisfaction; (5) interference with daytime functioning caused by sleep difficulties; (6) the visibility of sleep problems to others; and (7) distress caused by sleep difficulties. Each item is scored using a 5-point scale (0 = no problem to 4 = extremely severe problem), resulting in a total score of 0 to 28. The total ISI score (items (1)-(7)) and daytime functioning (items (4)-(7)) will be analyzed separately.

[0051] As used herein, the term “insomnia” means a disorder defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (2013; “DSM-V”), having the following diagnostic criteria: A. The subject's predominant complaint is dissatisfaction with the quantity or quality of sleep accompanied by one (or more) of the following symptoms: 1. Difficulty falling asleep (in children, this may manifest as difficulty falling asleep when no caregiver is present). 2. Characterized by difficulty maintaining sleep, frequent awakenings or problems falling asleep again after awakening (in children, this may manifest as difficulty falling asleep again when the caregiver is not present). 3. Early morning awakening with no ability to fall back asleep. B. The sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning. C. Sleep difficulties occur at least 3 nights per week. D. Sleep difficulties have persisted for at least 3 months. E. Sleep difficulties occur despite adequate sleep opportunities. F. The insomnia is not better explained by, and does not occur exclusively during, another sleep-wake disorder (e.g., narcolepsy, breathing-related sleep disorder, circadian rhythm sleep-wake disorder, parasomnia). G. The insomnia is not due to the physiological effects of a substance (e.g., a drug of abuse, medication). H. Coexistence of psychiatric and medical conditions does not fully explain the predominant complaint of insomnia.

[0052] The term "insomnia" also refers to a sleep disorder characterized by symptoms including, but not limited to, difficulty falling asleep, difficulty sleeping restfully, intermittent awakenings, and / or waking up too early. The term also encompasses daytime symptoms such as drowsiness, anxiety, difficulty concentrating, memory impairment, and irritability. Types of insomnia suitable for treatment with lemborexant or a pharmaceutically acceptable salt thereof include short-term insomnia and chronic insomnia.

[0053] As used herein, the term "latency to sustained sleep," abbreviated as "LPS," means the number of minutes from lights out to the first of 20 consecutive epochs (10 minutes) of non-wakefulness.

[0054] In some embodiments, sleep parameters are objectively determined using overnight polysomnography. Overnight polysomnography is the monitoring of multiple electrophysiological parameters during sleep, generally including EEG activity, electrooculogram activity, electromyogram activity, and other measurements. These results, along with observation, can be used to objectively measure the following: latency to persistent sleep (LPS), wake-up-after-sleep (WASO), wake-up-after-sleep-onset (WASO2H), sleep efficiency (SE) and total sleep time (TST).

[0055] As used herein, the term "about" means ±10% of the stated value. For example, in embodiments relating to a method in which subjective sleep onset latency is reduced by about 10 minutes, then subjective sleep onset latency is reduced by a time length ranging from 9 to 11 minutes.

[0056] As used herein, the term "immediately before going to bed" means within 5 minutes of starting to get ready for bed or getting into bed. In some embodiments, a patient takes lemborexant or a pharmaceutically acceptable salt thereof within 5 minutes of starting to get ready for bed. In some embodiments, a patient takes lemborexant or a pharmaceutically acceptable salt thereof within 2 minutes of starting to get ready for bed. In some embodiments, a patient takes lemborexant or a pharmaceutically acceptable salt thereof within 5 minutes of getting into bed. In some embodiments, a patient takes lemborexant or a pharmaceutically acceptable salt thereof within 2 minutes of getting into bed. In some embodiments, a patient takes lemborexant or a pharmaceutically acceptable salt thereof as soon as they get into bed.

[0057] How to reduce subjective sleep onset latency (sSOL) Provided herein are methods for reducing subjective sleep onset latency (sSOL) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof. Also disclosed herein are methods for reducing sSOL in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof.

[0058] In some embodiments, sSOL is reduced over at least one week. In some embodiments, sSOL is reduced over at least one month. In some embodiments, sSOL is reduced over at least two months. In some embodiments, sSOL is reduced over at least three months. In some embodiments, sSOL is reduced over at least six months. In some embodiments, sSOL is reduced over at least nine months. In some embodiments, sSOL is reduced over at least twelve months. In some embodiments, sSOL is reduced over at least eighteen months. In some embodiments, sSOL is reduced over two years or more.

[0059] In some embodiments, sSOL is decreased relative to baseline for at least 1 week. In some embodiments, sSOL is decreased relative to baseline for at least 1 month. In some embodiments, sSOL is decreased relative to baseline for at least 2 months. In some embodiments, sSOL is decreased relative to baseline for at least 3 months. In some embodiments, sSOL is decreased relative to baseline for at least 6 months. In some embodiments, sSOL is decreased relative to baseline for at least 9 months. In some embodiments, sSOL is decreased relative to baseline for at least 12 months. In some embodiments, sSOL is decreased relative to baseline for at least 18 months. In some embodiments, sSOL is decreased relative to baseline for more than 2 years.

[0060] In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 1 month. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 2 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for two or more years.

[0061] In some embodiments, sSOL is decreased relative to baseline by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes. In some embodiments, sSOL is decreased relative to baseline by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, at least 26 minutes, at least 27 minutes, at least 28 minutes, at least 29 minutes, at least 30 minutes, at least 31 minutes, at least 32 minutes, at least 33 minutes, at least 34 minutes, at least 35 minutes, at least 36 minutes, at least 37 minutes, at least 38 minutes, at least 39 minutes, at least 40 minutes, at least 41 minutes, at least 42 minutes, at least 43 minutes, at least 44 minutes, or at least 45 minutes.

[0062] In some embodiments, sSOL is decreased by at least 1 minute relative to baseline. In some embodiments, sSOL is decreased by at least 2 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 3 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 4 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 5 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 6 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 7 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 8 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 9 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 9 minutes relative to baseline.

[0063] In some embodiments, sSOL is decreased by at least 11 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 12 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 13 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 14 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 15 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 16 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 17 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 18 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 19 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 20 minutes relative to baseline.

[0064] In some embodiments, sSOL is decreased by at least 21 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 22 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 23 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 24 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 25 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 26 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 27 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 28 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 29 minutes relative to baseline.

[0065] In some embodiments, sSOL is decreased by at least 30 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 31 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 32 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 33 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 34 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 35 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 36 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 37 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 38 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 39 minutes relative to baseline. In some embodiments, sSOL is decreased by at least 40 minutes relative to baseline.

[0066] In some embodiments, sSOL is decreased by about 1 minute relative to baseline. In some embodiments, sSOL is decreased by about 2 minutes relative to baseline. In some embodiments, sSOL is decreased by about 3 minutes relative to baseline. In some embodiments, sSOL is decreased by about 4 minutes relative to baseline. In some embodiments, sSOL is decreased by about 5 minutes relative to baseline. In some embodiments, sSOL is decreased by about 6 minutes relative to baseline. In some embodiments, sSOL is decreased by about 7 minutes relative to baseline. In some embodiments, sSOL is decreased by about 8 minutes relative to baseline. In some embodiments, sSOL is decreased by about 9 minutes relative to baseline. In some embodiments, sSOL is decreased by about 9 minutes relative to baseline.

[0067] In some embodiments, sSOL is decreased by about 11 minutes relative to baseline. In some embodiments, sSOL is decreased by about 12 minutes relative to baseline. In some embodiments, sSOL is decreased by about 13 minutes relative to baseline. In some embodiments, sSOL is decreased by about 14 minutes relative to baseline. In some embodiments, sSOL is decreased by about 15 minutes relative to baseline. In some embodiments, sSOL is decreased by about 16 minutes relative to baseline. In some embodiments, sSOL is decreased by about 17 minutes relative to baseline. In some embodiments, sSOL is decreased by about 18 minutes relative to baseline. In some embodiments, sSOL is decreased by about 19 minutes relative to baseline. In some embodiments, sSOL is decreased by about 20 minutes relative to baseline.

[0068] In some embodiments, sSOL is decreased by about 21 minutes relative to baseline. In some embodiments, sSOL is decreased by about 22 minutes relative to baseline. In some embodiments, sSOL is decreased by about 23 minutes relative to baseline. In some embodiments, sSOL is decreased by about 24 minutes relative to baseline. In some embodiments, sSOL is decreased by about 25 minutes relative to baseline. In some embodiments, sSOL is decreased by about 26 minutes relative to baseline. In some embodiments, sSOL is decreased by about 27 minutes relative to baseline. In some embodiments, sSOL is decreased by about 28 minutes relative to baseline. In some embodiments, sSOL is decreased by about 29 minutes relative to baseline.

[0069] In some embodiments, sSOL is decreased by about 30 minutes relative to baseline. In some embodiments, sSOL is decreased by about 31 minutes relative to baseline. In some embodiments, sSOL is decreased by about 32 minutes relative to baseline. In some embodiments, sSOL is decreased by about 33 minutes relative to baseline. In some embodiments, sSOL is decreased by about 34 minutes relative to baseline. In some embodiments, sSOL is decreased by about 35 minutes relative to baseline. In some embodiments, sSOL is decreased by about 36 minutes relative to baseline. In some embodiments, sSOL is decreased by about 37 minutes relative to baseline. In some embodiments, sSOL is decreased by about 38 minutes relative to baseline. In some embodiments, sSOL is decreased by about 39 minutes relative to baseline. In some embodiments, sSOL is decreased by about 40 minutes relative to baseline.

[0070] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by about 20 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by about 25 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by about 30 minutes.

[0071] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by at least 20 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by at least 25 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by at least 30 minutes.

[0072] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by about 25 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by about 30 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by about 35 minutes.

[0073] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by at least 24 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by about 27 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sSOL is reduced by about 32 minutes.

[0074] In some embodiments, the sSOL is 1 minute or less, 2 minutes or less, 3 minutes or less, 4 minutes or less, 5 minutes or less, 5 minutes or less, 6 minutes or less, 7 minutes or less, 8 minutes or less, 9 minutes or less, 10 minutes or less, 11 minutes or less, 12 minutes or less, 13 minutes or less, 14 minutes or less, 15 minutes or less, 16 minutes or less, 17 minutes or less, 18 minutes or less, 19 minutes or less, 20 minutes or less, 21 minutes or less, 22 minutes or less, 23 minutes or less, 24 minutes or less, 25 minutes or less, 26 minutes or less, 27 minutes or less, 28 minutes or less, 29 minutes or less, 30 minutes or less, 31 minutes or less, 32 minutes or less, 33 minutes or less, 34 minutes or less, 35 minutes or less, 36 minutes or less, 37 minutes or less, 38 minutes or less, 39 minutes or less, 40 minutes or less, 41 minutes or less, 42 minutes or less, 43 minutes or less, 44 minutes or less, or 45 minutes or less.

[0075] In some embodiments, the sSOL is 1 minute or less. In some embodiments, the sSOL is 2 minutes or less. In some embodiments, the sSOL is 3 minutes or less. In some embodiments, the sSOL is 4 minutes or less. In some embodiments, the sSOL is 5 minutes or less. In some embodiments, the sSOL is 6 minutes or less. In some embodiments, the sSOL is 7 minutes or less. In some embodiments, the sSOL is 8 minutes or less. In some embodiments, the sSOL is 9 minutes or less. In some embodiments, the sSOL is 10 minutes or less.

[0076] In some embodiments, the sSOL is 11 minutes or less. In some embodiments, the sSOL is 12 minutes or less. In some embodiments, the sSOL is 13 minutes or less. In some embodiments, the sSOL is 14 minutes or less. In some embodiments, the sSOL is 15 minutes or less. In some embodiments, the sSOL is 16 minutes or less. In some embodiments, the sSOL is 17 minutes or less. In some embodiments, the sSOL is 18 minutes or less. In some embodiments, the sSOL is 19 minutes or less.

[0077] In some embodiments, the sSOL is 20 minutes or less. In some embodiments, the sSOL is 21 minutes or less. In some embodiments, the sSOL is 22 minutes or less. In some embodiments, the sSOL is 23 minutes or less. In some embodiments, the sSOL is 24 minutes or less. In some embodiments, the sSOL is 25 minutes or less. In some embodiments, the sSOL is 26 minutes or less. In some embodiments, the sSOL is 27 minutes or less. In some embodiments, the sSOL is 28 minutes or less. In some embodiments, the sSOL is 29 minutes or less.

[0078] In some embodiments, the sSOL is 30 minutes or less. In some embodiments, the sSOL is 31 minutes or less. In some embodiments, the sSOL is 32 minutes or less. In some embodiments, the sSOL is 33 minutes or less. In some embodiments, the sSOL is 34 minutes or less. In some embodiments, the sSOL is 35 minutes or less. In some embodiments, the sSOL is 36 minutes or less. In some embodiments, the sSOL is 37 minutes or less. In some embodiments, the sSOL is 38 minutes or less. In some embodiments, the sSOL is 39 minutes or less.

[0079] In some embodiments, the sSOL is 40 minutes or less. In some embodiments, the sSOL is 41 minutes or less. In some embodiments, the sSOL is 42 minutes or less. In some embodiments, the sSOL is 43 minutes or less. In some embodiments, the sSOL is 44 minutes or less. In some embodiments, the sSOL is 45 minutes or less.

[0080] In some embodiments, sSOL is administered in about 1 minute or less, about 2 minutes or less, about 3 minutes or less, about 4 minutes or less, about 5 minutes or less, about 6 minutes or less, about 7 minutes or less, about 8 minutes or less, about 9 minutes or less, about 10 minutes or less, about 11 minutes or less, about 12 minutes or less, about 13 minutes or less, about 14 minutes or less, about 15 minutes or less, about 16 minutes or less, about 17 minutes or less, about 18 minutes or less, about 19 minutes or less, about 20 minutes or less, about 21 minutes or less, about 22 minutes or less, about The reaction time is 23 minutes or less, about 24 minutes or less, about 25 minutes or less, about 26 minutes or less, about 27 minutes or less, about 28 minutes or less, about 29 minutes or less, about 30 minutes or less, about 31 minutes or less, about 32 minutes or less, about 33 minutes or less, about 34 minutes or less, about 35 minutes or less, about 36 minutes or less, about 37 minutes or less, about 38 minutes or less, about 39 minutes or less, about 40 minutes or less, about 41 minutes or less, about 42 minutes or less, about 43 minutes or less, about 44 minutes or less, or about 45 minutes or less.

[0081] In some embodiments, the sSOL is about 1 minute or less. In some embodiments, the sSOL is about 2 minutes or less. In some embodiments, the sSOL is about 3 minutes or less. In some embodiments, the sSOL is about 4 minutes or less. In some embodiments, the sSOL is about 5 minutes or less. In some embodiments, the sSOL is about 6 minutes or less. In some embodiments, the sSOL is about 7 minutes or less. In some embodiments, the sSOL is about 8 minutes or less. In some embodiments, the sSOL is about 9 minutes or less. In some embodiments, the sSOL is about 10 minutes or less.

[0082] In some embodiments, the sSOL is about 11 minutes or less. In some embodiments, the sSOL is about 12 minutes or less. In some embodiments, the sSOL is about 13 minutes or less. In some embodiments, the sSOL is about 14 minutes or less. In some embodiments, the sSOL is about 15 minutes or less. In some embodiments, the sSOL is about 16 minutes or less. In some embodiments, the sSOL is about 17 minutes or less. In some embodiments, the sSOL is about 18 minutes or less. In some embodiments, the sSOL is about 19 minutes or less.

[0083] In some embodiments, the sSOL is about 20 minutes or less. In some embodiments, the sSOL is about 21 minutes or less. In some embodiments, the sSOL is about 22 minutes or less. In some embodiments, the sSOL is about 23 minutes or less. In some embodiments, the sSOL is about 24 minutes or less. In some embodiments, the sSOL is about 25 minutes or less. In some embodiments, the sSOL is about 26 minutes or less. In some embodiments, the sSOL is about 27 minutes or less. In some embodiments, the sSOL is about 28 minutes or less. In some embodiments, the sSOL is about 29 minutes or less.

[0084] In some embodiments, the sSOL is about 30 minutes or less. In some embodiments, the sSOL is about 31 minutes or less. In some embodiments, the sSOL is about 32 minutes or less. In some embodiments, the sSOL is about 33 minutes or less. In some embodiments, the sSOL is about 34 minutes or less. In some embodiments, the sSOL is about 35 minutes or less. In some embodiments, the sSOL is about 36 minutes or less. In some embodiments, the sSOL is about 37 minutes or less. In some embodiments, the sSOL is about 38 minutes or less. In some embodiments, the sSOL is about 39 minutes or less.

[0085] In some embodiments, the sSOL is about 40 minutes or less. In some embodiments, the sSOL is about 41 minutes or less. In some embodiments, the sSOL is about 42 minutes or less. In some embodiments, the sSOL is about 43 minutes or less. In some embodiments, the sSOL is about 44 minutes or less. In some embodiments, the sSOL is about 45 minutes or less.

[0086] In some embodiments, the subject has insomnia.

[0087] How to reduce subjective wakefulness onset (sWASO) Provided herein are methods for reducing subjective wakefulness after sleep onset (sWASO) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof. Also disclosed herein are methods for reducing sWASO in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof.

[0088] In some embodiments, sWASO is reduced over at least 1 month. In some embodiments, sWASO is reduced over at least 2 months. In some embodiments, sWASO is reduced over at least 3 months. In some embodiments, sWASO is reduced over at least 6 months. In some embodiments, sWASO is reduced over at least 9 months. In some embodiments, sWASO is reduced over at least 12 months. In some embodiments, sWASO is reduced over at least 18 months. In some embodiments, sWASO is reduced over 2 years or more.

[0089] In some embodiments, sWASO is reduced relative to baseline for at least 1 month. In some embodiments, sWASO is reduced relative to baseline for at least 2 months. In some embodiments, sWASO is reduced relative to baseline for at least 3 months. In some embodiments, sWASO is reduced relative to baseline for at least 6 months. In some embodiments, sWASO is reduced relative to baseline for at least 9 months. In some embodiments, sWASO is reduced relative to baseline for at least 12 months. In some embodiments, sWASO is reduced relative to baseline for at least 18 months. In some embodiments, sWASO is reduced relative to baseline for more than 2 years.

[0090] In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 1 month. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 2 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for two or more years.

[0091] In some embodiments, sWASO is reduced relative to baseline by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes. In some embodiments, sWASO is reduced relative to baseline by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, at least 26 minutes, at least 27 minutes, at least 28 minutes, at least 29 minutes, or at least at least 30 minutes, at least 31 minutes, at least 32 minutes, at least 33 minutes, at least 34 minutes, at least 35 minutes, at least 36 minutes, at least 37 minutes, at least 38 minutes, at least 39 minutes, at least 40 minutes, at least 41 minutes, at least 42 minutes, at least 43 minutes, at least 44 minutes, at least 45 minutes, at least 46 minutes, at least 47 minutes, at least 48 minutes, at least 49 minutes, at least 50 minutes, at least 51 minutes, at least 52 minutes, at least 53 minutes, at least 54 minutes, at least 55 minutes, at least 56 minutes, at least 57 minutes, at least 58 minutes, at least 59 minutes or at least 60 minutes.

[0092] In some embodiments, sWASO is decreased by at least 1 minute relative to baseline. In some embodiments, sWASO is decreased by at least 2 minutes relative to baseline. In some embodiments, sWASO is decreased by at least 3 minutes relative to baseline. In some embodiments, sWASO is decreased by at least 4 minutes relative to baseline. In some embodiments, sWASO is decreased by at least 5 minutes relative to baseline. In some embodiments, sWASO is decreased by at least 6 minutes relative to baseline. In some embodiments, sWASO is decreased by at least 7 minutes relative to baseline. In some embodiments, sWASO is decreased by at least 8 minutes relative to baseline. In some embodiments, sWASO is decreased by at least 9 minutes relative to baseline. In some embodiments, sWASO is decreased by at least 9 minutes relative to baseline.

[0093] In some embodiments, sWASO is reduced by at least 11 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 12 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 13 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 14 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 15 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 16 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 17 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 18 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 19 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 20 minutes relative to baseline.

[0094] In some embodiments, sWASO is reduced by at least 21 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 22 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 23 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 24 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 25 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 26 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 27 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 28 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 29 minutes relative to baseline.

[0095] In some embodiments, sWASO is reduced by at least 30 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 31 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 32 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 33 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 34 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 35 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 36 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 37 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 38 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 39 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 40 minutes relative to baseline.

[0096] In some embodiments, sWASO is reduced by at least 41 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 42 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 43 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 44 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 45 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 46 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 47 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 48 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 49 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 50 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 51 minutes relative to baseline.

[0097] In some embodiments, sWASO is reduced by at least 52 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 53 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 54 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 55 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 56 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 57 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 58 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 59 minutes relative to baseline. In some embodiments, sWASO is reduced by at least 60 minutes relative to baseline.

[0098] In some embodiments, sWASO is decreased by about 1 minute relative to baseline. In some embodiments, sWASO is decreased by about 2 minutes relative to baseline. In some embodiments, sWASO is decreased by about 3 minutes relative to baseline. In some embodiments, sWASO is decreased by about 4 minutes relative to baseline. In some embodiments, sWASO is decreased by about 5 minutes relative to baseline. In some embodiments, sWASO is decreased by about 6 minutes relative to baseline. In some embodiments, sWASO is decreased by about 7 minutes relative to baseline. In some embodiments, sWASO is decreased by about 8 minutes relative to baseline. In some embodiments, sWASO is decreased by about 9 minutes relative to baseline. In some embodiments, sWASO is decreased by about 9 minutes relative to baseline.

[0099] In some embodiments, sWASO is decreased by about 11 minutes relative to baseline. In some embodiments, sWASO is decreased by about 12 minutes relative to baseline. In some embodiments, sWASO is decreased by about 13 minutes relative to baseline. In some embodiments, sWASO is decreased by about 14 minutes relative to baseline. In some embodiments, sWASO is decreased by about 15 minutes relative to baseline. In some embodiments, sWASO is decreased by about 16 minutes relative to baseline. In some embodiments, sWASO is decreased by about 17 minutes relative to baseline. In some embodiments, sWASO is decreased by about 18 minutes relative to baseline. In some embodiments, sWASO is decreased by about 19 minutes relative to baseline. In some embodiments, sWASO is decreased by about 20 minutes relative to baseline.

[0100] In some embodiments, sWASO is decreased by about 21 minutes relative to baseline. In some embodiments, sWASO is decreased by about 22 minutes relative to baseline. In some embodiments, sWASO is decreased by about 23 minutes relative to baseline. In some embodiments, sWASO is decreased by about 24 minutes relative to baseline. In some embodiments, sWASO is decreased by about 25 minutes relative to baseline. In some embodiments, sWASO is decreased by about 26 minutes relative to baseline. In some embodiments, sWASO is decreased by about 27 minutes relative to baseline. In some embodiments, sWASO is decreased by about 28 minutes relative to baseline. In some embodiments, sWASO is decreased by about 29 minutes relative to baseline.

[0101] In some embodiments, sWASO is decreased by about 30 minutes relative to baseline. In some embodiments, sWASO is decreased by about 31 minutes relative to baseline. In some embodiments, sWASO is decreased by about 32 minutes relative to baseline. In some embodiments, sWASO is decreased by about 33 minutes relative to baseline. In some embodiments, sWASO is decreased by about 34 minutes relative to baseline. In some embodiments, sWASO is decreased by about 35 minutes relative to baseline. In some embodiments, sWASO is decreased by about 36 minutes relative to baseline. In some embodiments, sWASO is decreased by about 37 minutes relative to baseline. In some embodiments, sWASO is decreased by about 38 minutes relative to baseline. In some embodiments, sWASO is decreased by about 39 minutes relative to baseline. In some embodiments, sWASO is decreased by about 40 minutes relative to baseline.

[0102] In some embodiments, sWASO is decreased by about 41 minutes relative to baseline. In some embodiments, sWASO is decreased by about 42 minutes relative to baseline. In some embodiments, sWASO is decreased by about 43 minutes relative to baseline. In some embodiments, sWASO is decreased by about 44 minutes relative to baseline. In some embodiments, sWASO is decreased by about 45 minutes relative to baseline. In some embodiments, sWASO is decreased by about 46 minutes relative to baseline. In some embodiments, sWASO is decreased by about 47 minutes relative to baseline. In some embodiments, sWASO is decreased by about 48 minutes relative to baseline. In some embodiments, sWASO is decreased by about 49 minutes relative to baseline. In some embodiments, sWASO is decreased by about 50 minutes relative to baseline. In some embodiments, sWASO is decreased by about 51 minutes relative to baseline.

[0103] In some embodiments, sWASO is decreased by about 52 minutes relative to baseline. In some embodiments, sWASO is decreased by about 53 minutes relative to baseline. In some embodiments, sWASO is decreased by about 54 minutes relative to baseline. In some embodiments, sWASO is decreased by about 55 minutes relative to baseline. In some embodiments, sWASO is decreased by about 56 minutes relative to baseline. In some embodiments, sWASO is decreased by about 57 minutes relative to baseline. In some embodiments, sWASO is decreased by about 58 minutes relative to baseline. In some embodiments, sWASO is decreased by about 59 minutes relative to baseline. In some embodiments, sWASO is decreased by about 60 minutes relative to baseline.

[0104] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by about 20 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by about 25 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by about 45 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by about 55 minutes.

[0105] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by at least 20 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by at least 23 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by at least 42 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by at least 51 minutes.

[0106] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by about 25 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by about 30 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by about 40 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced from baseline by about 50 minutes.

[0107] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by at least 23 minutes from baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by at least 26 minutes from baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by at least 39 minutes from baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by at least 48 minutes from baseline.

[0108] In some embodiments, sWASO is reduced relative to placebo by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes. In some embodiments, sWASO is reduced relative to placebo by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, at least 26 minutes, at least 27 minutes, at least 28 minutes, at least 29 minutes, or at least 30 minutes.

[0109] In some embodiments, sWASO is reduced by at least 1 minute relative to placebo. In some embodiments, sWASO is reduced by at least 2 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 3 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 4 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 5 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 6 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 7 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 8 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 9 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 10 minutes relative to placebo.

[0110] In some embodiments, sWASO is reduced by at least 11 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 12 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 13 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 14 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 15 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 16 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 17 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 18 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 19 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 20 minutes relative to placebo.

[0111] In some embodiments, sWASO is reduced by at least 21 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 22 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 23 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 24 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 25 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 26 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 27 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 28 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 29 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 30 minutes relative to placebo.

[0112] In some embodiments, sWASO is reduced by about 1 minute relative to placebo. In some embodiments, sWASO is reduced by about 2 minutes relative to placebo. In some embodiments, sWASO is reduced by about 3 minutes relative to placebo. In some embodiments, sWASO is reduced by about 4 minutes relative to placebo. In some embodiments, sWASO is reduced by about 5 minutes relative to placebo. In some embodiments, sWASO is reduced by about 6 minutes relative to placebo. In some embodiments, sWASO is reduced by about 7 minutes relative to placebo. In some embodiments, sWASO is reduced by about 8 minutes relative to baseline. In some embodiments, sWASO is reduced by about 9 minutes relative to baseline. In some embodiments, sWASO is reduced by about 10 minutes relative to placebo.

[0113] In some embodiments, sWASO is reduced by about 11 minutes relative to placebo. In some embodiments, sWASO is reduced by about 12 minutes relative to placebo. In some embodiments, sWASO is reduced by about 13 minutes relative to placebo. In some embodiments, sWASO is reduced by about 14 minutes relative to placebo. In some embodiments, sWASO is reduced by about 15 minutes relative to placebo. In some embodiments, sWASO is reduced by about 16 minutes relative to placebo. In some embodiments, sWASO is reduced by about 17 minutes relative to placebo. In some embodiments, sWASO is reduced by about 18 minutes relative to placebo. In some embodiments, sWASO is reduced by about 19 minutes relative to placebo. In some embodiments, sWASO is reduced by about 20 minutes relative to placebo.

[0114] In some embodiments, sWASO is reduced by about 21 minutes relative to placebo. In some embodiments, sWASO is reduced by about 22 minutes relative to placebo. In some embodiments, sWASO is reduced by about 23 minutes relative to placebo. In some embodiments, sWASO is reduced by about 24 minutes relative to placebo. In some embodiments, sWASO is reduced by about 25 minutes relative to placebo. In some embodiments, sWASO is reduced by about 26 minutes relative to placebo. In some embodiments, sWASO is reduced by about 27 minutes relative to placebo. In some embodiments, sWASO is reduced by about 28 minutes relative to placebo. In some embodiments, sWASO is reduced by about 29 minutes relative to placebo. In some embodiments, sWASO is reduced by about 30 minutes relative to placebo.

[0115] In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and sWASO is reduced by about 5 minutes relative to placebo. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and sWASO is reduced by about 15 minutes relative to placebo. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and sWASO is reduced by about 20 minutes relative to placebo.

[0116] In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and experiences a reduction in sWASO by at least 5 minutes relative to placebo. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and experiences a reduction in sWASO by at least 13 minutes relative to placebo. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and experiences a reduction in sWASO by at least 14 minutes relative to placebo. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and experiences a reduction in sWASO by at least 17 minutes relative to placebo.

[0117] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by about 5 minutes relative to placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by about 10 minutes relative to placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by about 15 minutes relative to placebo.

[0118] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by at least 7 minutes relative to placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by at least 10 minutes relative to placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by at least 12 minutes relative to placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and sWASO is reduced by at least 16 minutes relative to placebo.

[0119] In some embodiments, the subject has insomnia.

[0120] How to improve subjective sleep efficiency (sSE) Provided herein are methods for improving subjective sleep efficiency (sSE) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof. Also disclosed herein are methods for improving sSE in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof.

[0121] In some embodiments, sSE is improved for at least 1 month. In some embodiments, sSE is improved for at least 2 months. In some embodiments, sSE is improved for at least 3 months. In some embodiments, sSE is improved for at least 6 months. In some embodiments, sSE is improved for at least 9 months. In some embodiments, sSE is improved for at least 12 months. In some embodiments, sSE is improved for at least 18 months. In some embodiments, sSE is improved for more than 2 years.

[0122] In some embodiments, sSE is improved over at least 1 month relative to baseline. In some embodiments, sSE is improved over at least 2 months relative to baseline. In some embodiments, sSE is improved over at least 3 months relative to baseline. In some embodiments, sSE is improved over at least 6 months relative to baseline. In some embodiments, sSE is improved over at least 9 months relative to baseline. In some embodiments, sSE is improved over at least 12 months relative to baseline. In some embodiments, sSE is improved over at least 18 months relative to baseline. In some embodiments, sSE is improved over 2 years or more relative to baseline.

[0123] In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 1 month. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 2 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for two or more years.

[0124] In some embodiments, sSE is improved by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, or at least 50% relative to baseline. In some embodiments, sSE is improved by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21%, at least 22%, at least 23%, at least 24%, or at least 25% relative to baseline.

[0125] In some embodiments, sSE is improved by at least 1% relative to baseline. In some embodiments, sSE is improved by at least 2% relative to baseline. In some embodiments, sSE is improved by at least 3% relative to baseline. In some embodiments, sSE is improved by at least 4% relative to baseline. In some embodiments, sSE is improved by at least 5% relative to baseline. In some embodiments, sSE is improved by at least 6% relative to baseline. In some embodiments, sSE is improved by at least 7% relative to baseline. In some embodiments, sSE is improved by at least 8% relative to baseline. In some embodiments, sSE is improved by at least 9% relative to baseline.

[0126] In some embodiments, sSE is improved by at least 10% versus baseline. In some embodiments, sSE is improved by at least 11% versus baseline. In some embodiments, sSE is improved by at least 12% versus baseline. In some embodiments, sSE is improved by at least 13% versus baseline. In some embodiments, sSE is improved by at least 14% versus baseline. In some embodiments, sSE is improved by at least 15% versus baseline. In some embodiments, sSE is improved by at least 16% versus baseline. In some embodiments, sSE is improved by at least 17% versus baseline. In some embodiments, sSE is improved by at least 18% versus baseline. In some embodiments, sSE is improved by at least 19% versus baseline.

[0127] In some embodiments, sSE is improved by at least 20% versus baseline. In some embodiments, sSE is improved by at least 21% versus baseline. In some embodiments, sSE is improved by at least 22% versus baseline. In some embodiments, sSE is improved by at least 23% versus baseline. In some embodiments, sSE is improved by at least 24% versus baseline. In some embodiments, sSE is improved by at least 25% versus baseline.

[0128] In some embodiments, sSE is improved by about 1% relative to baseline. In some embodiments, sSE is improved by about 2% relative to baseline. In some embodiments, sSE is improved by about 3% relative to baseline. In some embodiments, sSE is improved by about 4% relative to baseline. In some embodiments, sSE is improved by about 5% relative to baseline. In some embodiments, sSE is improved by about 6% relative to baseline. In some embodiments, sSE is improved by about 7% relative to baseline. In some embodiments, sSE is improved by about 8% relative to baseline. In some embodiments, sSE is improved by about 9% relative to baseline.

[0129] In some embodiments, sSE is improved by about 10% versus baseline. In some embodiments, sSE is improved by about 11% versus baseline. In some embodiments, sSE is improved by about 12% versus baseline. In some embodiments, sSE is improved by about 13% versus baseline. In some embodiments, sSE is improved by about 14% versus baseline. In some embodiments, sSE is improved by about 15% versus baseline. In some embodiments, sSE is improved by about 16% versus baseline. In some embodiments, sSE is improved by about 17% versus baseline. In some embodiments, sSE is improved by about 18% versus baseline. In some embodiments, sSE is improved by about 19% versus baseline.

[0130] In some embodiments, sSE is improved by about 20% relative to baseline. In some embodiments, sSE is improved by about 21% relative to baseline. In some embodiments, sSE is improved by about 22% relative to baseline. In some embodiments, sSE is improved by about 23% relative to baseline. In some embodiments, sSE is improved by about 24% relative to baseline. In some embodiments, sSE is improved by about 25% relative to baseline.

[0131] In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by at least 6% compared to baseline. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by at least 7% compared to baseline. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by at least 13% compared to baseline. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by at least 15% compared to baseline.

[0132] In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by about 6% compared to baseline. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by about 7% compared to baseline. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by about 13% compared to baseline. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by about 15% compared to baseline.

[0133] In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by at least 8% compared to baseline. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by at least 9% compared to baseline. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by at least 13% compared to baseline. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by at least 15% compared to baseline.

[0134] In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by about 8% compared to baseline. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by about 9% compared to baseline. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by about 13% compared to baseline. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and sSE improves by about 15% compared to baseline.

[0135] In some embodiments, the sSE is improved by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, or at least 50% relative to placebo, hi some embodiments, the sSE is improved by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, or at least 10% relative to placebo.

[0136] In some embodiments, sSE is improved by at least 1% versus placebo. In some embodiments, sSE is improved by at least 2% versus placebo. In some embodiments, sSE is improved by at least 3% versus placebo. In some embodiments, sSE is improved by at least 4% versus placebo. In some embodiments, sSE is improved by at least 5% versus placebo.

[0137] In some embodiments, sSE is improved by at least 6% versus placebo. In some embodiments, sSE is improved by at least 7% versus placebo. In some embodiments, sSE is improved by at least 8% versus placebo. In some embodiments, sSE is improved by at least 9% versus placebo. In some embodiments, sSE is improved by at least 10% versus placebo.

[0138] In some embodiments, the sSE is improved by about 1% versus placebo. In some embodiments, the sSE is improved by about 2% versus placebo. In some embodiments, the sSE is improved by about 3% versus placebo. In some embodiments, the sSE is improved by about 4% versus placebo. In some embodiments, the sSE is improved by about 5% versus placebo.

[0139] In some embodiments, the sSE is improved by about 6% versus placebo. In some embodiments, the sSE is improved by about 7% versus placebo. In some embodiments, the sSE is improved by about 8% versus placebo. In some embodiments, the sSE is improved by about 9% versus placebo. In some embodiments, the sSE is improved by about 10% versus placebo.

[0140] In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the sSE is improved by at least 2% versus placebo. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the sSE is improved by at least 4% versus placebo.

[0141] In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and experiences at least a 2% improvement in sSE compared to baseline. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and experiences at least a 4% improvement in sSE compared to baseline.

[0142] In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the sSE is improved by at least 3% versus placebo. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the sSE is improved by at least 4% versus placebo. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the sSE is improved by at least 5% versus placebo.

[0143] In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the sSE is improved by at least 3% versus placebo. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the sSE is improved by at least 4% versus placebo. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the sSE is improved by at least 5% versus placebo.

[0144] Methods for reducing latency to persistent sleep (LPS) Provided herein are methods for reducing latency to persistent sleep (LPS) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof. Also disclosed herein are methods for reducing LPS in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof.

[0145] In some embodiments, the LPS is reduced over at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days. In some embodiments, the LPS is reduced over at least 1 day. In some embodiments, the LPS is reduced over at least 2 days. In some embodiments, the LPS is reduced over at least 3 days. In some embodiments, the LPS is reduced over at least 4 days. In some embodiments, the LPS is reduced over at least 5 days. In some embodiments, the LPS is reduced over at least 6 days. In some embodiments, the LPS is reduced over at least 7 days. In some embodiments, the LPS is reduced over a period of at least 8 days, in some embodiments, the LPS is reduced over a period of at least 9 days, in some embodiments, the LPS is reduced over a period of at least 10 days.

[0146] In some embodiments, the LPS is reduced over at least 11 days. In some embodiments, the LPS is reduced over at least 12 days. In some embodiments, the LPS is reduced over at least 13 days. In some embodiments, the LPS is reduced over at least 14 days. In some embodiments, the LPS is reduced over at least 15 days. In some embodiments, the LPS is reduced over at least 16 days. In some embodiments, the LPS is reduced over at least 17 days. In some embodiments, the LPS is reduced over at least 18 days. In some embodiments, the LPS is reduced over at least 19 days.

[0147] In some embodiments, the LPS is reduced over at least 20 days. In some embodiments, the LPS is reduced over at least 21 days. In some embodiments, the LPS is reduced over at least 22 days. In some embodiments, the LPS is reduced over at least 23 days. In some embodiments, the LPS is reduced over at least 24 days. In some embodiments, the LPS is reduced over at least 25 days. In some embodiments, the LPS is reduced over at least 26 days. In some embodiments, the LPS is reduced over at least 27 days. In some embodiments, the LPS is reduced over at least 28 days. In some embodiments, the LPS is reduced over at least 29 days. In some embodiments, the LPS is reduced over at least 30 days.

[0148] In some embodiments, the LPS is reduced over at least 1 month. In some embodiments, the LPS is reduced over at least 2 months. In some embodiments, the LPS is reduced over at least 3 months. In some embodiments, the LPS is reduced over at least 6 months. In some embodiments, the LPS is reduced over at least 9 months. In some embodiments, the LPS is reduced over at least 12 months. In some embodiments, the LPS is reduced over at least 18 months. In some embodiments, the LPS is reduced over 2 years or more.

[0149] In some embodiments, LPS is reduced over at least 1 month. In some embodiments, LPS is reduced over at least 2 months relative to baseline. In some embodiments, LPS is reduced over at least 3 months relative to baseline. In some embodiments, LPS is reduced over at least 6 months relative to baseline. In some embodiments, LPS is reduced over at least 9 months relative to baseline. In some embodiments, LPS is reduced over at least 12 months relative to baseline. In some embodiments, LPS is reduced over at least 18 months relative to baseline. In some embodiments, LPS is reduced over 2 years or more relative to baseline.

[0150] In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 1 month. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 2 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for two or more years.

[0151] In some embodiments, LPS is reduced relative to baseline by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes. In some embodiments, the LPS is decreased relative to baseline by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, at least 26 minutes, at least 27 minutes, at least 28 minutes, at least 29 minutes, at least 30 minutes, at least 31 minutes, at least 32 minutes, at least 33 minutes, at least 34 minutes, at least 35 minutes, at least 36 minutes, at least 37 minutes, at least 38 minutes, at least 39 minutes, at least 40 minutes, at least 41 minutes, at least 42 minutes, at least 43 minutes, at least 44 minutes, or at least 45 minutes.

[0152] In some embodiments, LPS is decreased relative to baseline for at least 1 minute. In some embodiments, LPS is decreased relative to baseline for at least 2 minutes. In some embodiments, LPS is decreased relative to baseline for at least 3 minutes. In some embodiments, LPS is decreased relative to baseline for at least 4 minutes. In some embodiments, LPS is decreased relative to baseline for at least 5 minutes. In some embodiments, LPS is decreased relative to baseline for at least 6 minutes. In some embodiments, LPS is decreased relative to baseline for at least 7 minutes. In some embodiments, LPS is decreased relative to baseline for at least 8 minutes. In some embodiments, LPS is decreased relative to baseline for at least 9 minutes. In some embodiments, LPS is decreased relative to baseline for at least 10 minutes.

[0153] In some embodiments, LPS is decreased by at least 11 minutes relative to baseline. In some embodiments, LPS is decreased by at least 12 minutes relative to baseline. In some embodiments, LPS is decreased by at least 13 minutes relative to baseline. In some embodiments, LPS is decreased by at least 14 minutes relative to baseline. In some embodiments, LPS is decreased by at least 15 minutes relative to baseline. In some embodiments, LPS is decreased by at least 16 minutes relative to baseline. In some embodiments, LPS is decreased by at least 17 minutes relative to baseline. In some embodiments, LPS is decreased by at least 18 minutes relative to baseline. In some embodiments, LPS is decreased by at least 19 minutes relative to baseline. In some embodiments, LPS is decreased by at least 20 minutes relative to baseline.

[0154] In some embodiments, LPS is decreased by at least 21 minutes relative to baseline. In some embodiments, LPS is decreased by at least 22 minutes relative to baseline. In some embodiments, LPS is decreased by at least 23 minutes relative to baseline. In some embodiments, LPS is decreased by at least 24 minutes relative to baseline. In some embodiments, LPS is decreased by at least 25 minutes relative to baseline. In some embodiments, LPS is decreased by at least 26 minutes relative to baseline. In some embodiments, LPS is decreased by at least 27 minutes relative to baseline. In some embodiments, LPS is decreased by at least 28 minutes relative to baseline. In some embodiments, LPS is decreased by at least 29 minutes relative to baseline.

[0155] In some embodiments, LPS is decreased by at least 30 minutes relative to baseline. In some embodiments, LPS is decreased by at least 31 minutes relative to baseline. In some embodiments, LPS is decreased by at least 32 minutes relative to baseline. In some embodiments, LPS is decreased by at least 33 minutes relative to baseline. In some embodiments, LPS is decreased by at least 34 minutes relative to baseline. In some embodiments, LPS is decreased by at least 35 minutes relative to baseline. In some embodiments, LPS is decreased by at least 36 minutes relative to baseline. In some embodiments, LPS is decreased by at least 37 minutes relative to baseline. In some embodiments, LPS is decreased by at least 38 minutes relative to baseline. In some embodiments, LPS is decreased by at least 39 minutes relative to baseline. In some embodiments, LPS is decreased by at least 40 minutes relative to baseline.

[0156] In some embodiments, the LPS is decreased relative to baseline by about 1 minute. In some embodiments, the LPS is decreased relative to baseline by about 2 minutes. In some embodiments, the LPS is decreased relative to baseline by about 3 minutes. In some embodiments, the LPS is decreased relative to baseline by about 4 minutes. In some embodiments, the LPS is decreased relative to baseline by about 5 minutes. In some embodiments, the LPS is decreased relative to baseline by about 6 minutes. In some embodiments, the LPS is decreased relative to baseline by about 7 minutes. In some embodiments, the LPS is decreased relative to baseline by about 8 minutes. In some embodiments, the LPS is decreased relative to baseline by about 9 minutes. In some embodiments, the LPS is decreased relative to baseline by about 10 minutes.

[0157] In some embodiments, LPS is decreased about 11 minutes relative to baseline. In some embodiments, LPS is decreased about 12 minutes relative to baseline. In some embodiments, LPS is decreased about 13 minutes relative to baseline. In some embodiments, LPS is decreased about 14 minutes relative to baseline. In some embodiments, LPS is decreased about 15 minutes relative to baseline. In some embodiments, LPS is decreased about 16 minutes relative to baseline. In some embodiments, LPS is decreased about 17 minutes relative to baseline. In some embodiments, LPS is decreased about 18 minutes relative to baseline. In some embodiments, LPS is decreased about 19 minutes relative to baseline. In some embodiments, LPS is decreased about 20 minutes relative to baseline.

[0158] In some embodiments, LPS is decreased by about 21 minutes relative to baseline. In some embodiments, LPS is decreased by about 22 minutes relative to baseline. In some embodiments, LPS is decreased by about 23 minutes relative to baseline. In some embodiments, LPS is decreased by about 24 minutes relative to baseline. In some embodiments, LPS is decreased by about 25 minutes relative to baseline. In some embodiments, LPS is decreased by about 26 minutes relative to baseline. In some embodiments, LPS is decreased by about 27 minutes relative to baseline. In some embodiments, LPS is decreased by about 28 minutes relative to baseline. In some embodiments, LPS is decreased by about 29 minutes relative to baseline.

[0159] In some embodiments, LPS is decreased relative to baseline by about 30 minutes. In some embodiments, LPS is decreased relative to baseline by about 31 minutes. In some embodiments, LPS is decreased relative to baseline by about 32 minutes. In some embodiments, LPS is decreased relative to baseline by about 33 minutes. In some embodiments, LPS is decreased relative to baseline by about 34 minutes. In some embodiments, LPS is decreased relative to baseline by about 35 minutes. In some embodiments, LPS is decreased relative to baseline by about 36 minutes. In some embodiments, LPS is decreased relative to baseline by about 37 minutes. In some embodiments, LPS is decreased relative to baseline by about 38 minutes. In some embodiments, LPS is decreased relative to baseline by about 39 minutes. In some embodiments, LPS is decreased relative to baseline by about 40 minutes.

[0160] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and LPS is reduced by about 16 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and LPS is reduced by about 19 minutes.

[0161] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and LPS is reduced by at least 16 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and LPS is reduced by at least 19 minutes.

[0162] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and LPS is reduced by about 19 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and LPS is reduced by about 21 minutes.

[0163] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and LPS is reduced by at least 19 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and LPS is reduced by at least 21 minutes.

[0164] In some embodiments, the LPS is 1 minute or less, 2 minutes or less, 3 minutes or less, 4 minutes or less, 5 minutes or less, 5 minutes or less, 6 minutes or less, 7 minutes or less, 8 minutes or less, 9 minutes or less, 10 minutes or less, 11 minutes or less, 12 minutes or less, 13 minutes or less, 14 minutes or less, 15 minutes or less, 16 minutes or less, 17 minutes or less, 18 minutes or less, 19 minutes or less, 20 minutes or less, 21 minutes or less, 22 minutes or less, 23 minutes or less, 24 minutes or less, 25 minutes or less, 26 minutes or less, 27 minutes or less, 28 minutes or less, 29 minutes or less, 30 minutes or less, 31 minutes or less, 32 minutes or less, 33 minutes or less, 34 minutes or less, 35 minutes or less, 36 minutes or less, 37 minutes or less, 38 minutes or less, 39 minutes or less, 40 minutes or less, 41 minutes or less, 42 minutes or less, 43 minutes or less, 44 minutes or less, or 45 minutes or less.

[0165] In some embodiments, the LPS is 1 minute or less. In some embodiments, the LPS is 2 minutes or less. In some embodiments, the LPS is 3 minutes or less. In some embodiments, the LPS is 4 minutes or less. In some embodiments, the LPS is 5 minutes or less. In some embodiments, the LPS is 6 minutes or less. In some embodiments, the LPS is 7 minutes or less. In some embodiments, the LPS is 8 minutes or less. In some embodiments, the LPS is 9 minutes or less. In some embodiments, the LPS is 10 minutes or less.

[0166] In some embodiments, the LPS is 11 minutes or less. In some embodiments, the LPS is 12 minutes or less. In some embodiments, the LPS is 13 minutes or less. In some embodiments, the LPS is 14 minutes or less. In some embodiments, the LPS is 15 minutes or less. In some embodiments, the LPS is 16 minutes or less. In some embodiments, the LPS is 17 minutes or less. In some embodiments, the LPS is 18 minutes or less. In some embodiments, the LPS is 19 minutes or less.

[0167] In some embodiments, the LPS is 20 minutes or less. In some embodiments, the LPS is 21 minutes or less. In some embodiments, the LPS is 22 minutes or less. In some embodiments, the LPS is 23 minutes or less. In some embodiments, the LPS is 24 minutes or less. In some embodiments, the LPS is 25 minutes or less. In some embodiments, the LPS is 26 minutes or less. In some embodiments, the LPS is 27 minutes or less. In some embodiments, the LPS is 28 minutes or less. In some embodiments, the LPS is 29 minutes or less.

[0168] In some embodiments, the LPS is 30 minutes or less. In some embodiments, the LPS is 31 minutes or less. In some embodiments, the LPS is 32 minutes or less. In some embodiments, the LPS is 33 minutes or less. In some embodiments, the LPS is 34 minutes or less. In some embodiments, the LPS is 35 minutes or less. In some embodiments, the LPS is 36 minutes or less. In some embodiments, the LPS is 37 minutes or less. In some embodiments, the LPS is 38 minutes or less. In some embodiments, the LPS is 39 minutes or less.

[0169] In some embodiments, the LPS is 40 minutes or less. In some embodiments, the LPS is 41 minutes or less. In some embodiments, the LPS is 42 minutes or less. In some embodiments, the LPS is 43 minutes or less. In some embodiments, the LPS is 44 minutes or less. In some embodiments, the LPS is 45 minutes or less.

[0170] In some embodiments, the LPS is lysed in about 1 minute or less, about 2 minutes or less, about 3 minutes or less, about 4 minutes or less, about 5 minutes or less, about 6 minutes or less, about 7 minutes or less, about 8 minutes or less, about 9 minutes or less, about 10 minutes or less, about 11 minutes or less, about 12 minutes or less, about 13 minutes or less, about 14 minutes or less, about 15 minutes or less, about 16 minutes or less, about 17 minutes or less, about 18 minutes or less, about 19 minutes or less, about 20 minutes or less, about 21 minutes or less, about 22 minutes or less, about The reaction time is 23 minutes or less, about 24 minutes or less, about 25 minutes or less, about 26 minutes or less, about 27 minutes or less, about 28 minutes or less, about 29 minutes or less, about 30 minutes or less, about 31 minutes or less, about 32 minutes or less, about 33 minutes or less, about 34 minutes or less, about 35 minutes or less, about 36 minutes or less, about 37 minutes or less, about 38 minutes or less, about 39 minutes or less, about 40 minutes or less, about 41 minutes or less, about 42 minutes or less, about 43 minutes or less, about 44 minutes or less, or about 45 minutes or less.

[0171] In some embodiments, the LPS is about 1 minute or less. In some embodiments, the LPS is about 2 minutes or less. In some embodiments, the LPS is about 3 minutes or less. In some embodiments, the LPS is about 4 minutes or less. In some embodiments, the LPS is about 5 minutes or less. In some embodiments, the LPS is about 6 minutes or less. In some embodiments, the LPS is about 7 minutes or less. In some embodiments, the LPS is about 8 minutes or less. In some embodiments, the LPS is about 9 minutes or less. In some embodiments, the LPS is about 10 minutes or less.

[0172] In some embodiments, the LPS is about 11 minutes or less. In some embodiments, the LPS is about 12 minutes or less. In some embodiments, the LPS is about 13 minutes or less. In some embodiments, the LPS is about 14 minutes or less. In some embodiments, the LPS is about 15 minutes or less. In some embodiments, the LPS is about 16 minutes or less. In some embodiments, the LPS is about 17 minutes or less. In some embodiments, the LPS is about 18 minutes or less. In some embodiments, the LPS is about 19 minutes or less.

[0173] In some embodiments, the LPS is about 20 minutes or less. In some embodiments, the LPS is about 21 minutes or less. In some embodiments, the LPS is about 22 minutes or less. In some embodiments, the LPS is about 23 minutes or less. In some embodiments, the LPS is about 24 minutes or less. In some embodiments, the LPS is about 25 minutes or less. In some embodiments, the LPS is about 26 minutes or less. In some embodiments, the LPS is about 27 minutes or less. In some embodiments, the LPS is about 28 minutes or less. In some embodiments, the LPS is about 29 minutes or less.

[0174] In some embodiments, the LPS is about 30 minutes or less. In some embodiments, the LPS is about 31 minutes or less. In some embodiments, the LPS is about 32 minutes or less. In some embodiments, the LPS is about 33 minutes or less. In some embodiments, the LPS is about 34 minutes or less. In some embodiments, the LPS is about 35 minutes or less. In some embodiments, the LPS is about 36 minutes or less. In some embodiments, the LPS is about 37 minutes or less. In some embodiments, the LPS is about 38 minutes or less. In some embodiments, the LPS is about 39 minutes or less.

[0175] In some embodiments, the LPS is about 40 minutes or less. In some embodiments, the LPS is about 41 minutes or less. In some embodiments, the LPS is about 42 minutes or less. In some embodiments, the LPS is about 43 minutes or less. In some embodiments, the LPS is about 44 minutes or less. In some embodiments, the LPS is about 45 minutes or less.

[0176] In some embodiments, the subject has insomnia.

[0177] How to reduce waking up on the night (WASO) Provided herein are methods for reducing Waking Up After Severe Anxiety (WASO) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof. Also disclosed herein are methods for reducing Waking Up After Severe Anxiety (WASO) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof.

[0178] In some embodiments, the WASO is decreased over at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days. In some embodiments, the WASO is decreased over at least 1 day. In some embodiments, the WASO is decreased over at least 2 days. In some embodiments, the WASO is decreased over at least 3 days. In some embodiments, the WASO is decreased over at least 4 days. In some embodiments, the WASO is decreased over at least 5 days. In some embodiments, the WASO is decreased over at least 6 days. In some embodiments, the WASO is decreased over at least 7 days. In some embodiments, the WASO is reduced over at least 8 days, in some embodiments, the WASO is reduced over at least 9 days, and in some embodiments, the WASO is reduced over at least 10 days.

[0179] In some embodiments, the WASO is reduced over at least 11 days. In some embodiments, the WASO is reduced over at least 12 days. In some embodiments, the WASO is reduced over at least 13 days. In some embodiments, the WASO is reduced over at least 14 days. In some embodiments, the WASO is reduced over at least 15 days. In some embodiments, the WASO is reduced over at least 16 days. In some embodiments, the WASO is reduced over at least 17 days. In some embodiments, the WASO is reduced over at least 18 days. In some embodiments, the WASO is reduced over at least 19 days.

[0180] In some embodiments, the WASO is reduced over at least 20 days. In some embodiments, the WASO is reduced over at least 21 days. In some embodiments, the WASO is reduced over at least 22 days. In some embodiments, the WASO is reduced over at least 23 days. In some embodiments, the WASO is reduced over at least 24 days. In some embodiments, the WASO is reduced over at least 25 days. In some embodiments, the WASO is reduced over at least 26 days. In some embodiments, the WASO is reduced over at least 27 days. In some embodiments, the WASO is reduced over at least 28 days. In some embodiments, the WASO is reduced over at least 29 days. In some embodiments, the WASO is reduced over at least 30 days.

[0181] In some embodiments, the WASO is decreased relative to baseline for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days. In some embodiments, the WASO is decreased relative to baseline for at least 1 day. In some embodiments, the WASO is decreased relative to baseline for at least 2 days. In some embodiments, the WASO is decreased relative to baseline for at least 3 days. In some embodiments, the WASO is decreased relative to baseline for at least 4 days. In some embodiments, the WASO is decreased relative to baseline for at least 5 days. In some embodiments, WASO is reduced relative to baseline for at least 6 days. In some embodiments, WASO is reduced relative to baseline for at least 7 days. In some embodiments, WASO is reduced relative to baseline for at least 8 days. In some embodiments, WASO is reduced relative to baseline for at least 9 days. In some embodiments, WASO is reduced relative to baseline for at least 10 days.

[0182] In some embodiments, WASO is reduced relative to baseline for at least 11 days. In some embodiments, WASO is reduced relative to baseline for at least 12 days. In some embodiments, WASO is reduced relative to baseline for at least 13 days. In some embodiments, WASO is reduced relative to baseline for at least 14 days. In some embodiments, WASO is reduced relative to baseline for at least 15 days. In some embodiments, WASO is reduced relative to baseline for at least 16 days. In some embodiments, WASO is reduced relative to baseline for at least 17 days. In some embodiments, WASO is reduced relative to baseline for at least 18 days. In some embodiments, WASO is reduced relative to baseline for at least 19 days.

[0183] In some embodiments, WASO is reduced relative to baseline for at least 20 days. In some embodiments, WASO is reduced relative to baseline for at least 21 days. In some embodiments, WASO is reduced relative to baseline for at least 22 days. In some embodiments, WASO is reduced relative to baseline for at least 23 days. In some embodiments, WASO is reduced relative to baseline for at least 24 days. In some embodiments, WASO is reduced relative to baseline for at least 25 days. In some embodiments, WASO is reduced relative to baseline for at least 26 days. In some embodiments, WASO is reduced relative to baseline for at least 27 days. In some embodiments, WASO is reduced relative to baseline for at least 28 days. In some embodiments, WASO is reduced relative to baseline for at least 29 days. In some embodiments, WASO is reduced relative to baseline for at least 30 days.

[0184] In some embodiments, WASO is reduced over at least 1 month. In some embodiments, WASO is reduced over at least 2 months. In some embodiments, WASO is reduced over at least 3 months. In some embodiments, WASO is reduced over at least 6 months. In some embodiments, WASO is reduced over at least 9 months. In some embodiments, WASO is reduced over at least 12 months. In some embodiments, WASO is reduced over at least 18 months. In some embodiments, WASO is reduced over 2 years or more.

[0185] In some embodiments, WASO is reduced relative to baseline for at least 1 month. In some embodiments, WASO is reduced relative to baseline for at least 2 months. In some embodiments, WASO is reduced relative to baseline for at least 3 months. In some embodiments, WASO is reduced relative to baseline for at least 6 months. In some embodiments, WASO is reduced relative to baseline for at least 9 months. In some embodiments, WASO is reduced relative to baseline for at least 12 months. In some embodiments, WASO is reduced relative to baseline for at least 18 months. In some embodiments, WASO is reduced relative to baseline for more than 2 years.

[0186] In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 1 month. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 2 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for two or more years.

[0187] In some embodiments, WASO is decreased relative to baseline by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes. In some embodiments, WASO is decreased relative to baseline by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, at least 26 minutes, at least 27 minutes, at least 28 minutes, at least 29 minutes, at least 30 minutes, at least 31 minutes, at least 32 minutes, at least 33 minutes, at least 34 minutes, or at least at least 35 minutes, at least 36 minutes, at least 37 minutes, at least 38 minutes, at least 39 minutes, at least 40 minutes, at least 41 minutes, at least 42 minutes, at least 43 minutes, at least 44 minutes, at least 45 minutes, at least 46 minutes, at least 47 minutes, at least 48 minutes, at least 49 minutes, at least 50 minutes, at least 51 minutes, at least 52 minutes, at least 53 minutes, at least 54 minutes, at least 55 minutes, at least 56 minutes, at least 57 minutes, at least 58 minutes, at least 59 minutes, at least 60 minutes, at least 61 minutes, at least 62 minutes, at least 63 minutes, at least 64 minutes, at least 65 minutes, at least 66 minutes, at least 67 minutes, at least 68 minutes, at least 69 minutes, or at least 70 minutes.

[0188] In some embodiments, the WASO is decreased by at least 1 minute relative to baseline. In some embodiments, the WASO is decreased by at least 2 minutes relative to baseline. In some embodiments, the WASO is decreased by at least 3 minutes relative to baseline. In some embodiments, the WASO is decreased by at least 4 minutes relative to baseline. In some embodiments, the WASO is decreased by at least 5 minutes relative to baseline. In some embodiments, the WASO is decreased by at least 6 minutes relative to baseline. In some embodiments, the WASO is decreased by at least 7 minutes relative to baseline. In some embodiments, the WASO is decreased by at least 8 minutes relative to baseline. In some embodiments, the WASO is decreased by at least 9 minutes relative to baseline. In some embodiments, the WASO is decreased by at least 10 minutes relative to baseline.

[0189] In some embodiments, WASO is reduced by at least 11 minutes relative to baseline. In some embodiments, WASO is reduced by at least 12 minutes relative to baseline. In some embodiments, WASO is reduced by at least 13 minutes relative to baseline. In some embodiments, WASO is reduced by at least 14 minutes relative to baseline. In some embodiments, WASO is reduced by at least 15 minutes relative to baseline. In some embodiments, WASO is reduced by at least 16 minutes relative to baseline. In some embodiments, WASO is reduced by at least 17 minutes relative to baseline. In some embodiments, WASO is reduced by at least 18 minutes relative to baseline. In some embodiments, WASO is reduced by at least 19 minutes relative to baseline. In some embodiments, WASO is reduced by at least 20 minutes relative to baseline.

[0190] In some embodiments, WASO is reduced by at least 21 minutes relative to baseline. In some embodiments, WASO is reduced by at least 22 minutes relative to baseline. In some embodiments, WASO is reduced by at least 23 minutes relative to baseline. In some embodiments, WASO is reduced by at least 24 minutes relative to baseline. In some embodiments, WASO is reduced by at least 25 minutes relative to baseline. In some embodiments, WASO is reduced by at least 26 minutes relative to baseline. In some embodiments, WASO is reduced by at least 27 minutes relative to baseline. In some embodiments, WASO is reduced by at least 28 minutes relative to baseline. In some embodiments, WASO is reduced by at least 29 minutes relative to baseline.

[0191] In some embodiments, the WASO is reduced by at least 30 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 31 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 32 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 33 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 34 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 35 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 36 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 37 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 38 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 39 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 40 minutes relative to baseline.

[0192] In some embodiments, the WASO is reduced by at least 41 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 42 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 43 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 44 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 45 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 46 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 47 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 48 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 49 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 50 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 51 minutes relative to baseline.

[0193] In some embodiments, the WASO is reduced by at least 52 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 53 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 54 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 55 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 56 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 57 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 58 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 59 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 60 minutes relative to baseline.

[0194] In some embodiments, the WASO is reduced by at least 61 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 62 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 63 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 64 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 65 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 66 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 67 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 68 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 69 minutes relative to baseline. In some embodiments, the WASO is reduced by at least 70 minutes relative to baseline.

[0195] In some embodiments, the WASO is decreased by about 1 minute relative to baseline. In some embodiments, the WASO is decreased by about 2 minutes relative to baseline. In some embodiments, the WASO is decreased by about 3 minutes relative to baseline. In some embodiments, the WASO is decreased by about 4 minutes relative to baseline. In some embodiments, the WASO is decreased by about 5 minutes relative to baseline. In some embodiments, the WASO is decreased by about 6 minutes relative to baseline. In some embodiments, the WASO is decreased by about 7 minutes relative to baseline. In some embodiments, the WASO is decreased by about 8 minutes relative to baseline. In some embodiments, the WASO is decreased by about 9 minutes relative to baseline. In some embodiments, the WASO is decreased by about 10 minutes relative to baseline.

[0196] In some embodiments, the WASO is decreased by about 11 minutes relative to baseline. In some embodiments, the WASO is decreased by about 12 minutes relative to baseline. In some embodiments, the WASO is decreased by about 13 minutes relative to baseline. In some embodiments, the WASO is decreased by about 14 minutes relative to baseline. In some embodiments, the WASO is decreased by about 15 minutes relative to baseline. In some embodiments, the WASO is decreased by about 16 minutes relative to baseline. In some embodiments, the WASO is decreased by about 17 minutes relative to baseline. In some embodiments, the WASO is decreased by about 18 minutes relative to baseline. In some embodiments, the WASO is decreased by about 19 minutes relative to baseline. In some embodiments, the WASO is decreased by about 20 minutes relative to baseline.

[0197] In some embodiments, the WASO is decreased by about 21 minutes relative to baseline. In some embodiments, the WASO is decreased by about 22 minutes relative to baseline. In some embodiments, the WASO is decreased by about 23 minutes relative to baseline. In some embodiments, the WASO is decreased by about 24 minutes relative to baseline. In some embodiments, the WASO is decreased by about 25 minutes relative to baseline. In some embodiments, the WASO is decreased by about 26 minutes relative to baseline. In some embodiments, the WASO is decreased by about 27 minutes relative to baseline. In some embodiments, the WASO is decreased by about 28 minutes relative to baseline. In some embodiments, the WASO is decreased by about 29 minutes relative to baseline.

[0198] In some embodiments, the WASO is decreased by about 30 minutes relative to baseline. In some embodiments, the WASO is decreased by about 31 minutes relative to baseline. In some embodiments, the WASO is decreased by about 32 minutes relative to baseline. In some embodiments, the WASO is decreased by about 33 minutes relative to baseline. In some embodiments, the WASO is decreased by about 34 minutes relative to baseline. In some embodiments, the WASO is decreased by about 35 minutes relative to baseline. In some embodiments, the WASO is decreased by about 36 minutes relative to baseline. In some embodiments, the WASO is decreased by about 37 minutes relative to baseline. In some embodiments, the WASO is decreased by about 38 minutes relative to baseline. In some embodiments, the WASO is decreased by about 39 minutes relative to baseline. In some embodiments, the WASO is decreased by about 40 minutes relative to baseline.

[0199] In some embodiments, the WASO is decreased by about 41 minutes relative to baseline. In some embodiments, the WASO is decreased by about 42 minutes relative to baseline. In some embodiments, the WASO is decreased by about 43 minutes relative to baseline. In some embodiments, the WASO is decreased by about 44 minutes relative to baseline. In some embodiments, the WASO is decreased by about 45 minutes relative to baseline. In some embodiments, the WASO is decreased by about 46 minutes relative to baseline. In some embodiments, the WASO is decreased by about 47 minutes relative to baseline. In some embodiments, the WASO is decreased by about 48 minutes relative to baseline. In some embodiments, the WASO is decreased by about 49 minutes relative to baseline. In some embodiments, the WASO is decreased by about 50 minutes relative to baseline. In some embodiments, the WASO is decreased by about 51 minutes relative to baseline.

[0200] In some embodiments, the WASO is decreased by about 52 minutes relative to baseline. In some embodiments, the WASO is decreased by about 53 minutes relative to baseline. In some embodiments, the WASO is decreased by about 54 minutes relative to baseline. In some embodiments, the WASO is decreased by about 55 minutes relative to baseline. In some embodiments, the WASO is decreased by about 56 minutes relative to baseline. In some embodiments, the WASO is decreased by about 57 minutes relative to baseline. In some embodiments, the WASO is decreased by about 58 minutes relative to baseline. In some embodiments, the WASO is decreased by about 59 minutes relative to baseline. In some embodiments, the WASO is decreased by about 60 minutes relative to baseline.

[0201] In some embodiments, the WASO is decreased by about 61 minutes relative to baseline. In some embodiments, the WASO is decreased by about 62 minutes relative to baseline. In some embodiments, the WASO is decreased by about 63 minutes relative to baseline. In some embodiments, the WASO is decreased by about 64 minutes relative to baseline. In some embodiments, the WASO is decreased by about 65 minutes relative to baseline. In some embodiments, the WASO is decreased by about 66 minutes relative to baseline. In some embodiments, the WASO is decreased by about 67 minutes relative to baseline. In some embodiments, the WASO is decreased by about 68 minutes relative to baseline. In some embodiments, the WASO is decreased by about 69 minutes relative to baseline. In some embodiments, the WASO is decreased by about 70 minutes relative to baseline.

[0202] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced from baseline by about 44 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced from baseline by about 50 minutes.

[0203] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced from baseline by at least 43 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced from baseline by at least 49 minutes.

[0204] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced from baseline by about 46 minutes, hi some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced from baseline by about 60 minutes.

[0205] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced from baseline by at least 46 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and sWASO is reduced from baseline by at least 59 minutes.

[0206] In some embodiments, WASO is reduced relative to placebo by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes. In some embodiments, WASO is reduced relative to placebo by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, at least 26 minutes, at least 27 minutes, at least 28 minutes, at least 29 minutes, at least 30 minutes, at least 31 minutes, at least 32 minutes, at least 33 minutes, at least 34 minutes, or at least 35 minutes.

[0207] In some embodiments, the WASO is reduced by at least 1 minute relative to placebo. In some embodiments, the WASO is reduced by at least 2 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 3 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 4 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 5 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 6 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 7 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 8 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 9 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 10 minutes relative to placebo.

[0208] In some embodiments, the WASO is reduced by at least 11 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 12 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 13 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 14 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 15 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 16 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 17 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 18 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 19 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 20 minutes relative to placebo.

[0209] In some embodiments, the WASO is reduced by at least 21 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 22 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 23 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 24 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 25 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 26 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 27 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 28 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 29 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 30 minutes relative to placebo.

[0210] In some embodiments, the WASO is reduced by at least 31 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 32 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 33 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 34 minutes relative to placebo. In some embodiments, the WASO is reduced by at least 35 minutes relative to placebo.

[0211] In some embodiments, WASO is reduced by about 1 minute relative to placebo. In some embodiments, WASO is reduced by about 2 minutes relative to placebo. In some embodiments, WASO is reduced by about 3 minutes relative to placebo. In some embodiments, WASO is reduced by about 4 minutes relative to placebo. In some embodiments, WASO is reduced by about 5 minutes relative to placebo. In some embodiments, WASO is reduced by about 6 minutes relative to placebo. In some embodiments, WASO is reduced by about 7 minutes relative to placebo. In some embodiments, WASO is reduced by about 8 minutes relative to baseline. In some embodiments, WASO is reduced by about 9 minutes relative to baseline. In some embodiments, WASO is reduced by about 10 minutes relative to placebo.

[0212] In some embodiments, the WASO is reduced by about 11 minutes relative to placebo. In some embodiments, the WASO is reduced by about 12 minutes relative to placebo. In some embodiments, the WASO is reduced by about 13 minutes relative to placebo. In some embodiments, the WASO is reduced by about 14 minutes relative to placebo. In some embodiments, the WASO is reduced by about 15 minutes relative to placebo. In some embodiments, the WASO is reduced by about 16 minutes relative to placebo. In some embodiments, the WASO is reduced by about 17 minutes relative to placebo. In some embodiments, the WASO is reduced by about 18 minutes relative to placebo. In some embodiments, the WASO is reduced by about 19 minutes relative to placebo. In some embodiments, the WASO is reduced by about 20 minutes relative to placebo.

[0213] In some embodiments, the WASO is reduced by about 21 minutes relative to placebo. In some embodiments, the WASO is reduced by about 22 minutes relative to placebo. In some embodiments, the WASO is reduced by about 23 minutes relative to placebo. In some embodiments, the WASO is reduced by about 24 minutes relative to placebo. In some embodiments, the WASO is reduced by about 25 minutes relative to placebo. In some embodiments, the WASO is reduced by about 26 minutes relative to placebo. In some embodiments, the WASO is reduced by about 27 minutes relative to placebo. In some embodiments, the WASO is reduced by about 28 minutes relative to placebo. In some embodiments, the WASO is reduced by about 29 minutes relative to placebo. In some embodiments, the WASO is reduced by about 30 minutes relative to placebo.

[0214] In some embodiments, the WASO is reduced by about 31 minutes relative to placebo. In some embodiments, the WASO is reduced by about 32 minutes relative to placebo. In some embodiments, the WASO is reduced by about 33 minutes relative to placebo. In some embodiments, the WASO is reduced by about 34 minutes relative to placebo. In some embodiments, the WASO is reduced by about 35 minutes relative to placebo.

[0215] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced by about 25 minutes relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced by about 35 minutes relative to placebo.

[0216] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced by at least 23 minutes relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced by at least 33 minutes relative to placebo.

[0217] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced by about 25 minutes relative to placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced by about 40 minutes relative to placebo.

[0218] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced by at least 25 minutes relative to placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced by at least 42 minutes relative to placebo.

[0219] In some embodiments, the WASO is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, or at least 25 minutes relative to zolpidem.

[0220] In some embodiments, the WASO is reduced by at least 1 minute relative to zolpidem. In some embodiments, the WASO is reduced by at least 2 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 3 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 4 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 5 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 6 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 7 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 8 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 9 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 10 minutes relative to zolpidem.

[0221] In some embodiments, the WASO is reduced by at least 11 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 12 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 13 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 14 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 15 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 16 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 17 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 18 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 19 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 20 minutes relative to zolpidem.

[0222] In some embodiments, the WASO is reduced by at least 21 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 22 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 23 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 24 minutes relative to zolpidem. In some embodiments, the WASO is reduced by at least 25 minutes relative to zolpidem.

[0223] In some embodiments, the WASO is reduced by about 1 minute relative to zolpidem. In some embodiments, the WASO is reduced by about 2 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 3 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 4 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 5 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 6 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 7 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 8 minutes relative to baseline. In some embodiments, the WASO is reduced by about 9 minutes relative to baseline. In some embodiments, the WASO is reduced by about 10 minutes relative to zolpidem.

[0224] In some embodiments, the WASO is reduced by about 11 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 12 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 13 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 14 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 15 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 16 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 17 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 18 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 19 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 20 minutes relative to zolpidem.

[0225] In some embodiments, the WASO is reduced by about 21 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 22 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 23 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 24 minutes relative to zolpidem. In some embodiments, the WASO is reduced by about 25 minutes relative to zolpidem.

[0226] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and the WASO is reduced by about 6 minutes relative to zolpidem. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and the WASO is reduced by about 7 minutes relative to zolpidem.

[0227] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced by at least 6 minutes relative to zolpidem. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced by at least 7 minutes relative to zolpidem.

[0228] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and WASO is reduced by about 10 minutes relative to zolpidem. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and WASO is reduced by about 15 minutes relative to zolpidem.

[0229] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced relative to zolpidem by at least 9 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO is reduced relative to zolpidem by at least 15 minutes.

[0230] In some embodiments, the subject has insomnia.

[0231] How to reduce wakefulness in the second half of the night (WASO2H) Provided herein are methods for reducing wakefulness during the second half of the night (WASO2H) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof. Also disclosed herein are methods for reducing WASO2H in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof.

[0232] In some embodiments, WASO2H is decreased over at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days. In some embodiments, WASO2H is decreased over at least 1 day. In some embodiments, WASO2H is decreased over at least 2 days. In some embodiments, WASO2H is decreased over at least 3 days. In some embodiments, WASO2H is decreased over at least 4 days. In some embodiments, WASO2H is decreased over at least 5 days. In some embodiments, WASO2H is decreased over at least 6 days. In some embodiments, WASO2H is decreased over at least 7 days, In some embodiments, WASO2H is decreased over at least 8 days, In some embodiments, WASO2H is decreased over at least 9 days, In some embodiments, WASO2H is decreased over at least 10 days.

[0233] In some embodiments, WASO2H is decreased over at least 11 days. In some embodiments, WASO2H is decreased over at least 12 days. In some embodiments, WASO2H is decreased over at least 13 days. In some embodiments, WASO2H is decreased over at least 14 days. In some embodiments, WASO2H is decreased over at least 15 days. In some embodiments, WASO2H is decreased over at least 16 days. In some embodiments, WASO2H is decreased over at least 17 days. In some embodiments, WASO2H is decreased over at least 18 days. In some embodiments, WASO2H is decreased over at least 19 days.

[0234] In some embodiments, WASO2H is decreased over a period of at least 20 days. In some embodiments, WASO2H is decreased over a period of at least 21 days. In some embodiments, WASO2H is decreased over a period of at least 22 days. In some embodiments, WASO2H is decreased over a period of at least 23 days. In some embodiments, WASO2H is decreased over a period of at least 24 days. In some embodiments, WASO2H is decreased over a period of at least 25 days. In some embodiments, WASO2H is decreased over a period of at least 26 days. In some embodiments, WASO2H is decreased over a period of at least 27 days. In some embodiments, WASO2H is decreased over a period of at least 28 days. In some embodiments, WASO2H is decreased over a period of at least 29 days. In some embodiments, WASO2H is decreased over a period of at least 30 days.

[0235] In some embodiments, WASO2H is decreased relative to baseline for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days. In some embodiments, WASO2H is decreased relative to baseline for at least 1 day. In some embodiments, WASO2H is decreased relative to baseline for at least 2 days. In some embodiments, WASO2H is decreased relative to baseline for at least 3 days. In some embodiments, WASO2H is decreased relative to baseline for at least 4 days. In some embodiments, WASO2H is decreased relative to baseline for at least 5 days. In some embodiments, WASO2H is decreased relative to baseline for at least 6 days. In some embodiments, WASO2H is decreased relative to baseline for at least 7 days. In some embodiments, WASO2H is decreased relative to baseline for at least 8 days. In some embodiments, WASO2H is decreased relative to baseline for at least 9 days. In some embodiments, WASO2H is decreased relative to baseline for at least 10 days.

[0236] In some embodiments, WASO2H is decreased relative to baseline for at least 11 days. In some embodiments, WASO2H is decreased relative to baseline for at least 12 days. In some embodiments, WASO2H is decreased relative to baseline for at least 13 days. In some embodiments, WASO2H is decreased relative to baseline for at least 14 days. In some embodiments, WASO2H is decreased relative to baseline for at least 15 days. In some embodiments, WASO2H is decreased relative to baseline for at least 16 days. In some embodiments, WASO2H is decreased relative to baseline for at least 17 days. In some embodiments, WASO2H is decreased relative to baseline for at least 18 days. In some embodiments, WASO2H is decreased relative to baseline for at least 19 days.

[0237] In some embodiments, WASO2H is decreased relative to baseline for at least 20 days. In some embodiments, WASO2H is decreased relative to baseline for at least 21 days. In some embodiments, WASO2H is decreased relative to baseline for at least 22 days. In some embodiments, WASO2H is decreased relative to baseline for at least 23 days. In some embodiments, WASO2H is decreased relative to baseline for at least 24 days. In some embodiments, WASO2H is decreased relative to baseline for at least 25 days. In some embodiments, WASO2H is decreased relative to baseline for at least 26 days. In some embodiments, WASO2H is decreased relative to baseline for at least 27 days. In some embodiments, WASO2H is decreased relative to baseline for at least 28 days. In some embodiments, WASO2H is decreased relative to baseline for at least 29 days. In some embodiments, WASO2H is decreased relative to baseline for at least 30 days.

[0238] In some embodiments, WASO2H is decreased over at least 1 month. In some embodiments, WASO2H is decreased over at least 2 months. In some embodiments, WASO2H is decreased over at least 3 months. In some embodiments, WASO2H is decreased over at least 6 months. In some embodiments, WASO2H is decreased over at least 9 months. In some embodiments, WASO2H is decreased over at least 12 months. In some embodiments, WASO2H is decreased over at least 18 months. In some embodiments, WASO2H is decreased over 2 years or more.

[0239] In some embodiments, WASO2H is decreased relative to baseline for at least 1 month. In some embodiments, WASO2H is decreased relative to baseline for at least 2 months. In some embodiments, WASO2H is decreased relative to baseline for at least 3 months. In some embodiments, WASO2H is decreased relative to baseline for at least 6 months. In some embodiments, WASO2H is decreased relative to baseline for at least 9 months. In some embodiments, WASO2H is decreased relative to baseline for at least 12 months. In some embodiments, WASO2H is decreased relative to baseline for at least 18 months. In some embodiments, WASO2H is decreased relative to baseline for more than 2 years.

[0240] In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 1 month. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 2 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for two or more years.

[0241] In some embodiments, WASO2H is decreased relative to baseline by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes. In some embodiments, WASO2H is decreased relative to baseline by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, at least 26 minutes, at least 27 minutes, at least 28 minutes, at least 29 minutes, at least 30 minutes, at least 31 minutes, at least 32 minutes, at least 33 minutes, at least 34 minutes, at least 35 minutes, at least 36 minutes, at least 37 minutes, at least 38 minutes, at least 39 minutes, at least 40 minutes, at least 41 minutes, at least 42 minutes, at least 43 minutes, at least 44 minutes, or at least 45 minutes.

[0242] In some embodiments, WASO2H is decreased relative to baseline by at least 1 minute. In some embodiments, WASO2H is decreased relative to baseline by at least 2 minutes. In some embodiments, WASO2H is decreased relative to baseline by at least 3 minutes. In some embodiments, WASO2H is decreased relative to baseline by at least 4 minutes. In some embodiments, WASO2H is decreased relative to baseline by at least 5 minutes. In some embodiments, WASO2H is decreased relative to baseline by at least 6 minutes. In some embodiments, WASO2H is decreased relative to baseline by at least 7 minutes. In some embodiments, WASO2H is decreased relative to baseline by at least 8 minutes. In some embodiments, WASO2H is decreased relative to baseline by at least 9 minutes. In some embodiments, WASO2H is decreased relative to baseline by at least 10 minutes.

[0243] In some embodiments, WASO2H is decreased by at least 11 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 12 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 13 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 14 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 15 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 16 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 17 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 18 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 19 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 20 minutes relative to baseline.

[0244] In some embodiments, WASO2H is decreased by at least 21 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 22 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 23 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 24 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 25 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 26 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 27 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 28 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 29 minutes relative to baseline.

[0245] In some embodiments, WASO2H is decreased by at least 30 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 31 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 32 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 33 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 34 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 35 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 36 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 37 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 38 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 39 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 40 minutes relative to baseline.

[0246] In some embodiments, WASO2H is decreased by at least 41 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 42 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 43 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 44 minutes relative to baseline. In some embodiments, WASO2H is decreased by at least 45 minutes relative to baseline.

[0247] In some embodiments, WASO2H is decreased by about 1 minute relative to baseline. In some embodiments, WASO2H is decreased by about 2 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 3 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 4 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 5 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 6 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 7 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 8 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 9 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 10 minutes relative to baseline.

[0248] In some embodiments, WASO2H is decreased by about 11 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 12 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 13 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 14 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 15 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 16 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 17 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 18 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 19 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 20 minutes relative to baseline.

[0249] In some embodiments, WASO2H is decreased by about 21 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 22 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 23 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 24 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 25 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 26 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 27 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 28 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 29 minutes relative to baseline.

[0250] In some embodiments, WASO2H is decreased by about 30 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 31 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 32 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 33 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 34 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 35 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 36 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 37 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 38 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 39 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 40 minutes relative to baseline.

[0251] In some embodiments, WASO2H is decreased by about 41 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 42 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 43 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 44 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 45 minutes relative to baseline.

[0252] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced from baseline by about 27 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced from baseline by about 30 minutes.

[0253] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced relative to baseline by at least 27 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced relative to baseline by at least 30 minutes.

[0254] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced from baseline by about 28 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced from baseline by about 37 minutes.

[0255] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced from baseline by at least 28 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and sWASO2H is reduced from baseline by at least 37 minutes.

[0256] In some embodiments, WASO2H is reduced relative to placebo by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes. In some embodiments, WASO2H is reduced relative to placebo by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, at least 26 minutes, at least 27 minutes, at least 28 minutes, at least 29 minutes, at least 30 minutes, at least 31 minutes, at least 32 minutes, at least 33 minutes, at least 34 minutes, or at least 35 minutes.

[0257] In some embodiments, WASO2H is decreased by at least 1 minute relative to placebo. In some embodiments, WASO2H is decreased by at least 2 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 3 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 4 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 5 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 6 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 7 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 8 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 9 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 10 minutes relative to placebo.

[0258] In some embodiments, WASO2H is decreased by at least 11 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 12 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 13 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 14 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 15 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 16 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 17 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 18 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 19 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 20 minutes relative to placebo.

[0259] In some embodiments, WASO2H is decreased by at least 21 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 22 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 23 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 24 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 25 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 26 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 27 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 28 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 29 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 30 minutes relative to placebo.

[0260] In some embodiments, WASO2H is decreased by at least 31 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 32 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 33 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 34 minutes relative to placebo. In some embodiments, WASO2H is decreased by at least 35 minutes relative to placebo.

[0261] In some embodiments, WASO2H is decreased by about 1 minute relative to placebo. In some embodiments, WASO2H is decreased by about 2 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 3 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 4 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 5 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 6 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 7 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 8 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 9 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 10 minutes relative to placebo.

[0262] In some embodiments, WASO2H is decreased by about 11 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 12 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 13 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 14 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 15 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 16 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 17 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 18 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 19 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 20 minutes relative to placebo.

[0263] In some embodiments, WASO2H is decreased by about 21 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 22 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 23 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 24 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 25 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 26 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 27 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 28 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 29 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 30 minutes relative to placebo.

[0264] In some embodiments, WASO2H is decreased by about 31 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 32 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 33 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 34 minutes relative to placebo. In some embodiments, WASO2H is decreased by about 35 minutes relative to placebo.

[0265] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced by about 16 minutes relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced by about 21 minutes relative to placebo.

[0266] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced by at least 16 minutes relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced by at least 21 minutes relative to placebo.

[0267] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced by about 17 minutes relative to placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced by about 28 minutes relative to placebo.

[0268] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced by at least 17 minutes relative to placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced by at least 28 minutes relative to placebo.

[0269] In some embodiments, WASO2H is decreased relative to zolpidem by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes. In some embodiments, WASO2H is decreased relative to zolpidem by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, or at least 25 minutes.

[0270] In some embodiments, WASO2H is decreased by at least 1 minute relative to zolpidem. In some embodiments, WASO2H is decreased by at least 2 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 3 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 4 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 5 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 6 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 7 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 8 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 9 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 10 minutes relative to zolpidem.

[0271] In some embodiments, WASO2H is decreased by at least 11 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 12 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 13 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 14 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 15 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 16 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 17 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 18 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 19 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 20 minutes relative to zolpidem.

[0272] In some embodiments, WASO2H is decreased by at least 21 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 22 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 23 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 24 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 25 minutes relative to zolpidem.

[0273] In some embodiments, WASO2H is decreased by about 1 minute relative to zolpidem. In some embodiments, WASO2H is decreased by about 2 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by about 3 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by about 4 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by about 5 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by about 6 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by about 7 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by about 8 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 9 minutes relative to baseline. In some embodiments, WASO2H is decreased by about 10 minutes relative to zolpidem.

[0274] In some embodiments, the WASO2H is decreased by about 11 minutes relative to zolpidem. In some embodiments, the WASO2H is decreased by about 12 minutes relative to zolpidem. In some embodiments, the WASO2H is decreased by about 13 minutes relative to zolpidem. In some embodiments, the WASO2H is decreased by about 14 minutes relative to zolpidem. In some embodiments, the WASO2H is decreased by about 15 minutes relative to zolpidem. In some embodiments, the WASO2H is decreased by about 16 minutes relative to zolpidem. In some embodiments, the WASO2H is decreased by about 17 minutes relative to zolpidem. In some embodiments, the WASO2H is decreased by about 18 minutes relative to zolpidem. In some embodiments, the WASO2H is decreased by about 19 minutes relative to zolpidem. In some embodiments, the WASO2H is decreased by about 20 minutes relative to zolpidem.

[0275] In some embodiments, WASO2H is decreased by about 21 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by about 22 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by about 23 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by about 24 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by about 25 minutes relative to zolpidem.

[0276] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and the WASO2H is reduced relative to zolpidem by about 6 minutes.

[0277] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and WASO2H is reduced relative to zolpidem by at least 6 minutes.

[0278] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and WASO2H is reduced by about 8 minutes relative to zolpidem. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject, and WASO2H is reduced by about 13 minutes relative to zolpidem.

[0279] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced by at least 8 minutes relative to zolpidem. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and WASO2H is reduced by at least 13 minutes relative to zolpidem.

[0280] In some embodiments, the subject has insomnia.

[0281] How to improve sleep efficiency (SE) Provided herein are methods for improving sleep efficiency (SE) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof.

[0282] In some embodiments, SE is improved for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days. In some embodiments, SE is improved for at least 1 day. In some embodiments, SE is improved for at least 2 days. In some embodiments, SE is improved for at least 3 days. In some embodiments, SE is improved for at least 4 days. In some embodiments, SE is improved for at least 5 days. In some embodiments, SE is improved for at least 6 days. In some embodiments, SE is improved for at least 7 days. In some embodiments, SE is improved for at least 8 days, In some embodiments, SE is improved for at least 9 days, In some embodiments, SE is improved for at least 10 days.

[0283] In some embodiments, SE is improved for at least 11 days. In some embodiments, SE is improved for at least 12 days. In some embodiments, SE is improved for at least 13 days. In some embodiments, SE is improved for at least 14 days. In some embodiments, SE is improved for at least 15 days. In some embodiments, SE is improved for at least 16 days. In some embodiments, SE is improved for at least 17 days. In some embodiments, SE is improved for at least 18 days. In some embodiments, SE is improved for at least 19 days.

[0284] In some embodiments, SE is improved for at least 20 days. In some embodiments, SE is improved for at least 21 days. In some embodiments, SE is improved for at least 22 days. In some embodiments, SE is improved for at least 23 days. In some embodiments, SE is improved for at least 24 days. In some embodiments, SE is improved for at least 25 days. In some embodiments, SE is improved for at least 26 days. In some embodiments, SE is improved for at least 27 days. In some embodiments, SE is improved for at least 28 days. In some embodiments, SE is improved for at least 29 days. In some embodiments, SE is improved for at least 30 days.

[0285] In some embodiments, SE is improved for at least 1 month. In some embodiments, SE is improved for at least 2 months. In some embodiments, SE is improved for at least 3 months. In some embodiments, SE is improved for at least 6 months. In some embodiments, SE is improved for at least 9 months. In some embodiments, SE is improved for at least 12 months. In some embodiments, SE is improved for at least 18 months. In some embodiments, SE is improved for more than 2 years.

[0286] In some embodiments, SE is improved for at least 1 month. In some embodiments, SE is improved for at least 2 months relative to baseline. In some embodiments, SE is improved for at least 3 months relative to baseline. In some embodiments, SE is improved for at least 6 months relative to baseline. In some embodiments, SE is improved for at least 9 months relative to baseline. In some embodiments, SE is improved for at least 12 months relative to baseline. In some embodiments, SE is improved for at least 18 months relative to baseline. In some embodiments, SE is improved for more than 2 years relative to baseline.

[0287] In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 1 month. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 2 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to a subject for two or more years.

[0288] In some embodiments, SE is improved by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, or at least 50% relative to baseline. In some embodiments, SE is improved by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21%, at least 22%, at least 23%, at least 24%, or at least 25% relative to baseline.

[0289] In some embodiments, SE is improved by at least 1% relative to baseline. In some embodiments, SE is improved by at least 2% relative to baseline. In some embodiments, SE is improved by at least 3% relative to baseline. In some embodiments, SE is improved by at least 4% relative to baseline. In some embodiments, SE is improved by at least 5% relative to baseline. In some embodiments, SE is improved by at least 6% relative to baseline. In some embodiments, SE is improved by at least 7% relative to baseline. In some embodiments, SE is improved by at least 8% relative to baseline. In some embodiments, SE is improved by at least 9% relative to baseline.

[0290] In some embodiments, SE is improved by at least 10% versus baseline. In some embodiments, SE is improved by at least 11% versus baseline. In some embodiments, SE is improved by at least 12% versus baseline. In some embodiments, SE is improved by at least 13% versus baseline. In some embodiments, SE is improved by at least 14% versus baseline. In some embodiments, SE is improved by at least 15% versus baseline. In some embodiments, SE is improved by at least 16% versus baseline. In some embodiments, SE is improved by at least 17% versus baseline. In some embodiments, SE is improved by at least 18% versus baseline. In some embodiments, SE is improved by at least 19% versus baseline.

[0291] In some embodiments, SE is improved by at least 20% versus baseline. In some embodiments, SE is improved by at least 21% versus baseline. In some embodiments, SE is improved by at least 22% versus baseline. In some embodiments, SE is improved by at least 23% versus baseline. In some embodiments, SE is improved by at least 24% versus baseline. In some embodiments, SE is improved by at least 25% versus baseline.

[0292] In some embodiments, SE is improved by about 1% relative to baseline. In some embodiments, SE is improved by about 2% relative to baseline. In some embodiments, SE is improved by about 3% relative to baseline. In some embodiments, SE is improved by about 4% relative to baseline. In some embodiments, SE is improved by about 5% relative to baseline. In some embodiments, SE is improved by about 6% relative to baseline. In some embodiments, SE is improved by about 7% relative to baseline. In some embodiments, SE is improved by about 8% relative to baseline. In some embodiments, SE is improved by about 9% relative to baseline.

[0293] In some embodiments, SE is improved by about 10% relative to baseline. In some embodiments, SE is improved by about 11% relative to baseline. In some embodiments, SE is improved by about 12% relative to baseline. In some embodiments, SE is improved by about 13% relative to baseline. In some embodiments, SE is improved by about 14% relative to baseline. In some embodiments, SE is improved by about 15% relative to baseline. In some embodiments, SE is improved by about 16% relative to baseline. In some embodiments, SE is improved by about 17% relative to baseline. In some embodiments, SE is improved by about 18% relative to baseline. In some embodiments, SE is improved by about 19% relative to baseline.

[0294] In some embodiments, SE is improved by about 20% versus baseline. In some embodiments, SE is improved by about 21% versus baseline. In some embodiments, SE is improved by about 22% versus baseline. In some embodiments, SE is improved by about 23% versus baseline. In some embodiments, SE is improved by about 24% versus baseline. In some embodiments, SE is improved by about 25% versus baseline.

[0295] In some embodiments, 5 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, is administered to a subject, and SE improves by at least 12% versus baseline.

[0296] In some embodiments, 5 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, is administered to a subject, and SE improves by about 12% versus baseline.

[0297] In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and experiences at least a 14% improvement in SE compared to baseline. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and experiences at least a 15% improvement in SE compared to baseline.

[0298] In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and experiences an improvement in SE of about 14% versus baseline. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and experiences an improvement in SE of about 15% versus baseline.

[0299] In some embodiments, SE is improved by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, or at least 50% relative to placebo. In some embodiments, SE is improved by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21%, at least 22%, at least 23%, at least 24%, or at least 25% relative to placebo.

[0300] In some embodiments, SE is improved by at least 1% versus placebo. In some embodiments, SE is improved by at least 2% versus placebo. In some embodiments, SE is improved by at least 3% versus placebo. In some embodiments, SE is improved by at least 4% versus placebo. In some embodiments, SE is improved by at least 5% versus placebo.

[0301] In some embodiments, SE is improved by at least 6% versus placebo. In some embodiments, SE is improved by at least 7% versus placebo. In some embodiments, SE is improved by at least 8% versus placebo. In some embodiments, SE is improved by at least 9% versus placebo. In some embodiments, SE is improved by at least 10% versus placebo.

[0302] In some embodiments, SE is improved by at least 11% versus placebo. In some embodiments, SE is improved by at least 12% versus placebo. In some embodiments, SE is improved by at least 13% versus placebo. In some embodiments, SE is improved by at least 14% versus placebo. In some embodiments, SE is improved by at least 15% versus placebo.

[0303] In some embodiments, SE is improved by at least 16% versus placebo. In some embodiments, SE is improved by at least 17% versus placebo. In some embodiments, SE is improved by at least 18% versus placebo. In some embodiments, SE is improved by at least 19% versus placebo. In some embodiments, SE is improved by at least 20% versus placebo.

[0304] In some embodiments, SE is improved by at least 21% versus placebo. In some embodiments, SE is improved by at least 22% versus placebo. In some embodiments, SE is improved by at least 23% versus placebo. In some embodiments, SE is improved by at least 24% versus placebo. In some embodiments, SE is improved by at least 25% versus placebo.

[0305] In some embodiments, SE is improved by about 1% versus placebo. In some embodiments, SE is improved by about 2% versus placebo. In some embodiments, SE is improved by about 3% versus placebo. In some embodiments, SE is improved by about 4% versus placebo. In some embodiments, SE is improved by about 5% versus placebo.

[0306] In some embodiments, SE is improved by about 6% versus placebo. In some embodiments, SE is improved by about 7% versus placebo. In some embodiments, SE is improved by about 8% versus placebo. In some embodiments, SE is improved by about 9% versus placebo. In some embodiments, SE is improved by about 10% versus placebo.

[0307] In some embodiments, SE is improved by about 11% versus placebo. In some embodiments, SE is improved by about 12% versus placebo. In some embodiments, SE is improved by about 13% versus placebo. In some embodiments, SE is improved by about 14% versus placebo. In some embodiments, SE is improved by about 15% versus placebo.

[0308] In some embodiments, SE is improved by about 16% versus placebo. In some embodiments, SE is improved by about 17% versus placebo. In some embodiments, SE is improved by about 18% versus placebo. In some embodiments, SE is improved by about 19% versus placebo. In some embodiments, SE is improved by about 20% versus placebo.

[0309] In some embodiments, SE is improved by about 21% versus placebo. In some embodiments, SE is improved by about 22% versus placebo. In some embodiments, SE is improved by about 23% versus placebo. In some embodiments, SE is improved by about 24% versus placebo. In some embodiments, SE is improved by about 25% versus placebo.

[0310] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and SE is improved by at least 7% versus placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and SE is improved by at least 9% versus placebo.

[0311] In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and has an SE improvement of about 7% versus placebo. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and has an SE improvement of about 9% versus placebo.

[0312] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and SE is improved by at least 8% versus placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and SE is improved by at least 8% versus placebo.

[0313] In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and there is about an 8% improvement in SE versus placebo. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and there is about an 11% improvement in SE versus placebo.

[0314] In some embodiments, the SE is improved by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, or at least 50% relative to zolpidem. In some embodiments, the SE is improved by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, or at least 15% relative to zolpidem.

[0315] In some embodiments, the SE is improved by at least 1% relative to zolpidem. In some embodiments, the SE is improved by at least 2% relative to zolpidem. In some embodiments, the SE is improved by at least 3% relative to zolpidem. In some embodiments, the SE is improved by at least 4% relative to zolpidem. In some embodiments, the SE is improved by at least 5% relative to zolpidem.

[0316] In some embodiments, the SE is improved by at least 6% relative to zolpidem. In some embodiments, the SE is improved by at least 7% relative to zolpidem. In some embodiments, the SE is improved by at least 8% relative to zolpidem. In some embodiments, the SE is improved by at least 9% relative to zolpidem. In some embodiments, the SE is improved by at least 10% relative to zolpidem.

[0317] In some embodiments, the SE is improved by at least 11% relative to zolpidem. In some embodiments, the SE is improved by at least 12% relative to zolpidem. In some embodiments, the SE is improved by at least 13% relative to zolpidem. In some embodiments, the SE is improved by at least 14% relative to zolpidem. In some embodiments, the SE is improved by at least 15% relative to zolpidem.

[0318] In some embodiments, the SE is improved by about 1% relative to zolpidem. In some embodiments, the SE is improved by about 2% relative to zolpidem. In some embodiments, the SE is improved by about 3% relative to zolpidem. In some embodiments, the SE is improved by about 4% relative to zolpidem. In some embodiments, the SE is improved by about 5% relative to zolpidem.

[0319] In some embodiments, the SE is improved by about 6% relative to zolpidem. In some embodiments, the SE is improved by about 7% relative to zolpidem. In some embodiments, the SE is improved by about 8% relative to zolpidem. In some embodiments, the SE is improved by about 9% relative to zolpidem. In some embodiments, the SE is improved by about 10% relative to zolpidem.

[0320] In some embodiments, the SE is improved by about 11% relative to zolpidem. In some embodiments, the SE is improved by about 12% relative to zolpidem. In some embodiments, the SE is improved by about 13% relative to zolpidem. In some embodiments, the SE is improved by about 14% relative to zolpidem. In some embodiments, the SE is improved by about 15% relative to zolpidem.

[0321] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and SE is improved by at least 2% relative to zolpidem. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and SE is improved by at least 3% relative to zolpidem.

[0322] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 2% relative to zolpidem. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 4% relative to zolpidem.

[0323] In some embodiments, 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, is administered to a subject, and SE is improved by at least 4% relative to zolpidem.

[0324] In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 4% relative to zolpidem. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 5% relative to zolpidem.

[0325] Other embodiments Embodiment 1. A method of reducing subjective sleep onset latency (sSOL) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein sSOL is reduced relative to baseline for at least 1 month.

[0326] Embodiment 2. The method of embodiment 1, wherein sSOL is decreased relative to baseline for at least 6 months.

[0327] Embodiment 3 The method of embodiment 1, wherein lemborexant or a salt thereof is administered to the subject for at least 1 month.

[0328] Embodiment 4 The method of embodiment 2, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

[0329] Embodiment 5. The method of embodiment 1, wherein the sSOL is reduced by at least 20 minutes.

[0330] Embodiment 6. The method of embodiment 1, wherein the sSOL is 40 minutes or less.

[0331] Embodiment 7. The method of embodiment 6, wherein the sSOL is 25 minutes or less.

[0332] Embodiment 8. The method of embodiment 1, wherein the subject has insomnia.

[0333] Embodiment 9. A method of improving subjective sleep efficiency (sSE) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein sSE is increased relative to baseline for at least 1 month.

[0334] Embodiment 10. The method of embodiment 9, wherein sSE is increased over at least 6 months relative to baseline.

[0335] Embodiment 11 The method of embodiment 9, wherein lemborexant or a salt thereof is administered to the subject for at least 1 month.

[0336] Embodiment 12 The method of embodiment 10, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

[0337] Embodiment 13. The method of embodiment 9, wherein sSE is improved by at least 13%.

[0338] Embodiment 14. The method of embodiment 9, wherein the subject has insomnia.

[0339] Embodiment 15. A method of reducing subjective wakefulness after onset (sWASO) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein sWASO is reduced relative to baseline for at least 1 month.

[0340] Embodiment 16. The method of embodiment 15, wherein sWASO is reduced relative to baseline for at least 6 months.

[0341] Embodiment 17 The method of embodiment 15, wherein lemborexant or a salt thereof is administered to the subject for at least 1 month.

[0342] Embodiment 18. The method of embodiment 16, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

[0343] Embodiment 19. The method of embodiment 15, wherein the sWASO is reduced by at least 40 minutes.

[0344] Embodiment 20. The method of embodiment 15, wherein the subject has insomnia.

[0345] Embodiment 21. Lemborexant or a pharmaceutically acceptable salt thereof for use in reducing subjective sleep onset latency (sSOL) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein sSOL is reduced relative to baseline for at least 1 month.

[0346] Embodiment 22. The use of embodiment 21, wherein sSOL is reduced relative to baseline for at least 6 months.

[0347] Embodiment 23. The use of embodiment 21, wherein lemborexant or a salt thereof is administered to the subject for at least 1 month.

[0348] Embodiment 24. The use of embodiment 22, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

[0349] Embodiment 25. The use of embodiment 21, wherein sSOL is reduced by at least 20 minutes.

[0350] Embodiment 26. The use of embodiment 21, wherein the subject has insomnia.

[0351] Embodiment 27. Lemborexant or a pharmaceutically acceptable salt thereof for improving subjective sleep efficiency (sSE) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein sSE is increased relative to baseline for at least 1 month.

[0352] Embodiment 28. The use of embodiment 27, wherein sSE is increased over at least 6 months relative to baseline.

[0353] Embodiment 29. The use of embodiment 27, wherein lemborexant or a salt thereof is administered to the subject for at least 1 month.

[0354] Embodiment 30. The use of embodiment 28, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

[0355] Embodiment 31. The use according to embodiment 27, wherein sSE is improved by at least 13%.

[0356] Embodiment 32. The use of embodiment 27, wherein the subject has insomnia.

[0357] Embodiment 33. Lemborexant or a pharmaceutically acceptable salt thereof for reducing subjective wakefulness after onset (sWASO) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein sWASO is reduced relative to baseline for at least 1 month.

[0358] Embodiment 34. The use of embodiment 33, wherein sWASO is reduced relative to baseline for at least 6 months.

[0359] Embodiment 35. The use of embodiment 33, wherein lemborexant or a salt thereof is administered to the subject for at least 1 month.

[0360] Embodiment 36. The use of embodiment 34, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

[0361] Embodiment 37. The use according to embodiment 33, wherein the sWASO is reduced by at least 40 minutes.

[0362] Embodiment 38. The use of embodiment 33, wherein the subject has insomnia.

[0363] Embodiment 39. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of maintaining a reduction in the time to fall asleep as measured by subjective sleep onset latency (sSOL) compared to placebo over at least one month of treatment.

[0364] Embodiment 40. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving a sustained reduction in time to fall asleep as measured by subjective sleep onset latency (sSOL) compared to placebo through 6 months of treatment.

[0365] Embodiment 41. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for at least one month, and wherein the dosage form is achievable in terms of maintaining a reduction in time to fall asleep as measured by subjective sleep onset latency (sSOL) compared to placebo during at least one month of treatment.

[0366] Embodiment 42. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form may be administered to a patient for 6 months, and wherein the dosage form is achievable in terms of maintaining a reduction in time to fall asleep as measured by subjective sleep onset latency (sSOL) compared to placebo throughout the 6 months of treatment.

[0367] Embodiment 43. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of maintaining an improvement in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo over at least one month of treatment.

[0368] Embodiment 44. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvements in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo through 6 months of treatment.

[0369] Embodiment 45. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for at least one month, and wherein the dosage form is achievable in terms of maintaining an improvement in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo over at least one month of treatment.

[0370] Embodiment 46. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for 6 months, and wherein the dosage form is capable of maintaining an improvement in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo throughout the 6 months of treatment.

[0371] Embodiment 47. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvement in wake after sleep onset (sWASO) compared to placebo over at least one month of treatment.

[0372] Embodiment 48. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvement in wake after sleep onset (sWASO) compared to placebo through 6 months of treatment.

[0373] Embodiment 49. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for at least one month, and wherein the dosage form is achievable in terms of sustained improvement in wake after sleep onset (sWASO) compared to placebo over at least one month of treatment.

[0374] Embodiment 50. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for 6 months, and wherein the dosage form is achievable in terms of sustained improvement in wake after sleep onset (sWASO) compared to placebo throughout the 6 months of treatment.

[0375] Embodiment 51. A method of treating insomnia in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep onset latency is reduced relative to baseline for at least 1 month.

[0376] Embodiment 52. A method of treating insomnia in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep efficiency is increased relative to baseline for at least 1 month.

[0377] Embodiment 53. A method of treating insomnia in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective awakenings after sleep are reduced relative to baseline for at least 1 month.

[0378] Embodiment 54. A method of identifying a subject responsive to treatment with lemborexant or a pharmaceutically acceptable salt thereof, comprising: a) To determine the subject's pre-treatment subjective wake-onset score (sWASO); b) if the pre-treatment period sWASO is 60 minutes or greater, administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof for the treatment period; c) To determine the subjects' sWASO after the treatment period; d) If the post-treatment sWASO is less than 60 minutes and the post-treatment sWASO is at least 10 minutes shorter than the pre-treatment sWASO, administer 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof to the subject. A method comprising:

[0379] Embodiment 55. The method of embodiment 54, wherein the post-treatment period sWASO is at least 20 minutes shorter than the pre-treatment period sWASO.

[0380] Embodiment 56. The method of embodiment 54, wherein the post-treatment period sWASO is at least 30 minutes shorter than the pre-treatment period sWASO.

[0381] Embodiment 57. The method of embodiment 54, wherein pre-treatment period subjective sleep efficiency (sSE) is determined prior to administering lemborexant or a pharmaceutically acceptable salt thereof.

[0382] Embodiment 58. The method of embodiment 57, wherein sSE is determined after a treatment period following administration of lemborexant or a pharmaceutically acceptable salt thereof.

[0383] Embodiment 59. The method of embodiment 55, wherein the post-treatment period sSE is improved by at least 10% relative to the pre-treatment period sSE.

[0384] Embodiment 60. The method of embodiment 55, wherein the post-treatment period sSE is improved by at least 14% relative to the pre-treatment period sSE.

[0385] Embodiment 61 The method of embodiment 54, wherein a pre-treatment period subjective sleep onset latency (sSOL) is determined prior to administering lemborexant or a pharmaceutically acceptable salt thereof.

[0386] Embodiment 62. The method of embodiment 61, wherein sSOL is determined after a treatment period following administration of lemborexant or a pharmaceutically acceptable salt thereof.

[0387] Embodiment 63. The method of embodiment 62, wherein the post-treatment period sSOL is at least 15 minutes shorter than the pre-treatment period sSOL.

[0388] Embodiment 64. The method of embodiment 62, wherein the post-treatment period sSOL is at least 20 minutes shorter than the pre-treatment period sSOL.

[0389] Embodiment 65. A method of treating insomnia in a subject in need thereof, comprising: a) To determine the subject's pre-treatment subjective sleep onset latency (sSOL); b) administering to the subject an oral dosage form containing 5 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, within 15 minutes before the subject's bedtime, wherein the subject remains in bed for at least 7 hours; c) To determine the subject's sSOL after the treatment period; d) administering to the subject an oral dosage form containing 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, within 15 minutes before the subject's bedtime, wherein the subject remains in bed for at least 7 hours, if post-treatment sSOL is not reduced relative to pre-treatment sSOL and the subject does not experience serious adverse reactions. Includes; Post-treatment sSOL decreased over at least one month compared to pre-treatment sSOL. The method involves a decrease in sSOL after the treatment period of 15 minutes or more relative to the sSOL before the treatment period.

[0390] Embodiment 66. The method of embodiment 65, wherein the sSOL after the treatment period is reduced relative to the sSOL before the treatment period by 20 minutes or more.

[0391] Embodiment 67. The method of embodiment 65, wherein the sSOL after the treatment period is 40 minutes or less.

[0392] Embodiment 68. The method of embodiment 67, wherein the sSOL after the treatment period is 25 minutes or less.

[0393] Embodiment 69. A method of treating insomnia in a subject in need thereof, comprising: a) To determine the subject's pre-treatment subjective sleep efficiency (sSE); b) administering to the subject an oral dosage form containing 5 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, within 15 minutes before the subject's bedtime, wherein the subject remains in bed for at least 7 hours; c) determining the subject's sSE after the treatment period; d) administering to the subject an oral dosage form containing 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, within 15 minutes before the subject's bedtime, wherein the subject remains in bed for at least 7 hours, if post-treatment sSOL is not increased relative to pre-treatment sSE and the subject does not experience serious adverse reactions. Includes; The post-treatment sSE increased over the pre-treatment sSE for at least 1 month. The post-treatment sSE is increased by 8% or more relative to the pre-treatment sSE.

[0394] Embodiment 70. The method of embodiment 69, wherein the sSE after the treatment period is increased by 13% or more relative to the sSE before the treatment period.

[0395] Embodiment 71. A method of treating insomnia in a subject in need thereof, comprising: a) To determine the subject's pre-treatment subjective wake-onset score (sWASO); b) administering to the subject an oral dosage form containing 5 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, within 15 minutes before the subject's bedtime, wherein the subject remains in bed for at least 7 hours; c) To determine the subjects' sWASO after the treatment period; d) If post-treatment sSOL is not reduced relative to pre-treatment sWASO and the subject does not experience serious adverse reactions, administering to the subject an oral dosage form containing 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, within 15 minutes before the subject's bedtime, wherein the subject remains in bed for at least 7 hours. Includes; Post-treatment sWASO was reduced for at least 1 month compared to pre-treatment sWASO. The method wherein the post-treatment period sWASO is reduced by at least 29 minutes relative to the pre-treatment period sWASO.

[0396] Embodiment 72. The method of embodiment 71, wherein the post-treatment period sWASO is reduced by at least 40 minutes relative to the pre-treatment period sWASO.

[0397] Embodiment 7 A method of treating insomnia comprising orally administering a dosage form containing 3.5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to a patient no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining until the planned wake-up time, where if the 5 mg dose is well tolerated but not effective, the dose may thereafter be increased to 10 mg once daily; The dosage form is achievable in maintaining a reduction in the time to fall asleep as measured by subjective sleep onset latency (sSOL) for at least one month of treatment; sSOL decreases by at least 15 minutes relative to baseline.

[0398] Embodiment 7 A method of treating insomnia comprising orally administering a dosage form containing 4.5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to a patient no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining until the planned wake-up time, where if the 5 mg dose is well tolerated but not effective, the dose may thereafter be increased to 10 mg once daily; The dosage form is achievable in terms of maintaining improvements in sleep efficiency in subjective sleep efficiency (sSE) over at least one month of treatment; sSE is improved by at least 4% over the baseline.

[0399] Embodiment 7 A method of treating insomnia comprising orally administering a dosage form containing 5.5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to a patient no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining until the planned wake-up time, where if the 5 mg dose is well tolerated but not effective, the dose may thereafter be increased to 10 mg once daily; The dosage form is achievable in maintaining improvement in subjective wakefulness after onset (sWASO) for at least one month of treatment; sWASO decreases by at least 29 minutes relative to baseline.

[0400] Embodiment 7 A method of treating insomnia comprising orally administering a dosage form containing 6.5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to a patient not more than once per night immediately prior to going to bed with at least 7 hours remaining until the patient's planned wake-up time; The daily dose may be increased to 10 mg based on clinical response and tolerability, and the dosage form is achievable in maintaining a reduction in time to sleep onset in subjective sleep onset latency (sSOL) for at least one month of treatment.

[0401] Embodiment 77. The method of embodiment 76, wherein the dosage form is achievable with respect to maintaining a reduction in the time to fall asleep as measured by subjective sleep onset latency (sSOL) over at least 6 months of treatment.

[0402] Embodiment 78. The method of embodiment 76, wherein the dosage form can be administered to the patient for at least one month.

[0403] Embodiment 79. The method of embodiment 76, wherein the dosage form can be administered to the patient for at least 6 months.

[0404] Embodiment 80. The method of embodiment 76, wherein sSOL is decreased relative to baseline by at least 15 minutes.

[0405] Embodiment 8 A method of treating insomnia comprising orally administering a dosage form containing 1.5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to a patient not more than once per night immediately prior to going to bed with at least 7 hours remaining until the patient's planned wake-up time; The daily dose may be increased to 10 mg based on clinical response and tolerability. The method, wherein the dosage form is achievable with respect to maintaining improvements in sleep efficiency in subjective sleep efficiency (sSE) over at least one month of treatment.

[0406] Embodiment 82. The method of embodiment 81, wherein the dosage form is achievable with respect to maintaining improvements in sleep efficiency in subjective sleep efficiency (sSE) over at least one month of treatment.

[0407] Embodiment 83. The method of embodiment 81, wherein the dosage form can be administered to the patient for at least one month.

[0408] Embodiment 84. The method of embodiment 81, wherein the dosage form can be administered to the patient for at least 6 months.

[0409] Embodiment 85. The method of embodiment 81, wherein sSE is improved by at least 4% over baseline.

[0410] Embodiment 8 A method of treating insomnia comprising orally administering a dosage form containing 6.5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to a patient not more than once per night immediately prior to going to bed with at least 7 hours remaining until the patient's planned wake-up time; The daily dose may be increased to 10 mg based on clinical response and tolerability. The dosage form is achievable in terms of maintaining improvement in subjective wakefulness after onset (sWASO) for at least one month of treatment.

[0411] Embodiment 87. The method of embodiment 86, wherein the dosage form is achievable with respect to maintaining improvements in sleep efficiency in subjective sleep efficiency (sSE) over at least one month of treatment.

[0412] Embodiment 88. The method of embodiment 86, wherein the dosage form can be administered to the patient for at least one month.

[0413] Embodiment 89. The method of embodiment 86, wherein the dosage form can be administered to the patient for at least 6 months.

[0414] Embodiment 90. The method of embodiment 86, wherein sWASO is reduced by at least 29 minutes relative to baseline.

[0415] In order that the disclosure described herein may be more fully understood, the following examples are set forth. It should be understood that these examples are for illustrative purposes only and are not to be construed as limiting the disclosure in any way. [Example]

[0416] Abbreviations and Definitions As used herein, the following abbreviations and definitions shall apply unless otherwise indicated.

[0417] eC-SSRS - Electronic Columbia-Suicide Severity Rating Scale: A self-rating suicidality scale that assesses an individual's degree of suicidality, including both suicidal ideation and suicidal behavior.

[0418] EQ-5D-3L - Health-Related Quality of Life Assessment: An instrument that can be used in clinical and economic decisions about health care and to collect data on quality of life and preferences / utilities. This instrument includes questions about mobility, self-care, daily activities, pain / discomfort, and anxiety / depression, and a visual analog scale ranging from 0 ("worst imaginable health") to 100 ("best imaginable health").

[0419] LPS - Latency of sustained sleep: minutes from lights out to the first of 20 consecutive epochs of non-wakefulness.

[0420] PGI-Insomnia - Patient Global Impression Insomnia: A self-report assessment asking subjects how they felt about the effect of the study medication on their sleep compared to their sleep before entering the study. The PGI-Insomnia has three items regarding the effect of the study medication (a: improved / worsened sleep, b: decreased / increased time to fall asleep, and c: increased / decreased TST) and one item with a different 3-point scale (1 = good medication effect, 2 = neutral medication effect, 3 = poor medication effect) and a final item (medication: 1 = too strong, 2 = just right, 3 = too weak). Each item was reported separately.

[0421] SAE - Serious Adverse Event

[0422] SDSB - Sleep Disorders Screening Battery

[0423] SE - Sleep efficiency: TST / proportion of time asleep per total time in bed calculated as lights off to lights on interval.

[0424] sSE - Subjective Sleep Efficiency: The ratio of sTST per subjective time in bed calculated as the interval from when the subject reports attempting to sleep to when the subject stops trying to sleep that night (operationalized as when the subject gets out of bed that day) and time spent asleep derived by subtracting sWASO from subjective time in bed.

[0425] sSOL - Subjective Sleep Onset Latency: An estimate in minutes from when the subject attempts to fall asleep to when they fall asleep.

[0426] sTST - Subjective Total Sleep Time: Derived minutes of sleep from sleep onset to the point when the subject stopped trying to sleep that night.

[0427] sWASO - Subjective Awake on Sleep: The sum of estimated minutes of wakefulness during the night after initial sleep onset to the point at which the subject stopped trying to sleep that night, operationalized as the point at which the subject got out of bed that day.

[0428] T-BWSQ - Tyrer Benzodiazepine Withdrawal Symptom Questionnaire: A questionnaire designed to assess withdrawal symptoms following discontinuation of a study drug. Tyrer, P. et al. "The benzodiazepine withdrawal symptom questionnaire." J. Affect. Disord. 1990;19(1):53-61.

[0429] TEAE - Treatment-emergent adverse events

[0430] TST - Total Sleep Time: minutes of sleep from sleep onset to end of wakefulness.

[0431] WASO - Awake onset: minutes of wakefulness from the onset of continuous sleep to light on.

[0432] WASO2H: Second half of the night wakefulness: minutes awake during the interval from 240 minutes after lights out to lights on.

[0433] WPAI-GH - Work Productivity and Activity Impairment Questionnaire-General Health: Collects data on absenteeism and presenteeism. This scale contains six items that result in four scores. Results are expressed as a disability rate, with higher numbers indicating greater disability and lower productivity. The four scores include: (1) percent work-hour absence due to health reasons; (2) percent work-related disability due to health reasons; (3) percent overall work-related disability due to health reasons; and (4) percent activity-related disability due to health reasons.

[0434] Example 1. Treatment of a subject with an insomnia disorder Subjects of both sexes aged 18 years and older, with approximately 40% of the population aged 65 years and older, were screened for eligibility for treatment. 971 subjects were randomized to treatment; however, only 949 subjects were in the full analysis set. Demographic information for the subject population is shown in Table 1.

[0435] The study consisted of a pre-randomization phase and a randomization phase.

[0436] Pre-randomization phase The pre-randomization phase consisted of three periods: a screening period, a run-in period, and a baseline period.

[0437] Screening Period The screening period begins within 35 days before the randomization of the subject.The subject is assessed based on the eligibility criteria and other assessments (for example, sleep disorder screening battery), and if the subject is deemed eligible, the subject is instructed on how to keep a sleep diary and report the measurements of the sleep parameters discussed herein.Subsequently, the subject proceeds to the run-in period.

[0438] Implementation period The run-in period began when eligible subjects received a placebo tablet each night immediately before bedtime for at least 13 nights. During the run-in period, subjects were required to remain in bed for at least 7 hours each night and maintain a regular bedtime.

[0439] Baseline period After treatment with placebo during the run-in period, subjects were assessed (e.g., Insomnia Severity Index, clinical blood and urine tests, vital signs, weight, and electrocardiogram) and, if still eligible, proceeded to the randomization phase.

[0440] Randomization Phase The randomized phase consisted of two periods: Treatment Period 1 and Treatment Period 2. The randomized phase lasted for 12 months.

[0441] Subjects were randomized in a double-blind manner to receive placebo, 5 mg lemborexant, or 10 mg lemborexant (approximately 1:1:1 randomization). All subjects underwent routine safety monitoring throughout the study, including evaluation of treatment-emergent adverse events, 12-lead electrocardiograms, vital signs, weight, and clinical hematology and blood chemistry tests. Suicidality was assessed using the eC-SSRS.

[0442] Treatment period 1 Treatment Period 1 began with the first dose of randomized study medication (placebo, 5 mg lemborexant, or 10 mg lemborexant). Subjects completed a sleep diary each morning within 1 hour of awakening. Subjects were evaluated by a clinician 1, 2, 3, and 6 months after the start of Treatment Period 1. The following assessments were performed:

[0443] Month 1 Assessment: Subjects underwent standard safety assessments. Blood samples were collected to determine plasma concentrations of lemborexant and its metabolites, and the ISI, FSS, PGI-Insomnia, EQ-5D-3L, and eC-SSR were completed.

[0444] Month 2 Assessment: Standard safety assessments were performed on subjects.

[0445] Month 3 Assessment: All assessments performed at the month 1 assessment were repeated.

[0446] Six-month assessment: All assessments performed at the one-month assessment were repeated and subjects completed the WPAI-GH.

[0447] After the 6-month evaluation was completed, treatment period 1 ended and treatment period 2 began.

[0448] Treatment period 2 At the end of the second-month assessment in Treatment Period 1 (Treatment Period 2 Baseline), subjects who received placebo in Treatment Period 1 underwent a second randomization to receive either 5 mg or 10 mg of lemborexant. Subjects who received lemborexant during Treatment Period 1 continued to receive the same dose of lemborexant.

[0449] During Treatment Period 2, subjects continued to complete sleep diaries as they did during Treatment Period 1. Subjects were evaluated during the 9-month and 12-month evaluations. At Months 7, 8, 10, and 11, clinicians discussed treatment by phone (e.g., sleep diaries, concomitant medications, adverse events).

[0450] During the 9- and 12-month evaluations, the safety and tolerability of lemborexant were assessed, the ec-SSR was completed, urine drug testing was performed, and subjects also completed the ISI, FSS, EQ-5D-3L, PGI-Insomnia, and WPAI-GH. Blood samples (for pharmacokinetic analysis) were also collected.

[0451] Early drug discontinuation Subjects who prematurely discontinued study medication at any time after the start of the randomization phase were asked to return to their clinician within 7 days of discontinuation and were encouraged to continue completing all study assessments (except for blood sample collection), including the sleep diary.

[0452] Follow-up period The follow-up period began at the end of Treatment Period 2. Subjects stopped taking study medication; however, they continued to complete their sleep diaries each morning until the end-of-study visit.

[0453] End of study visit Subjects were evaluated 14-18 days after completing Treatment Period 2. In addition to standard safety assessments and completion of the eC-SSRS, urine drug screening was performed, the T-BWSQ was administered, and sleep diaries were collected.

[0454] Target population Inclusion criteria Subjects were eligible to participate in the study if they met all of the following inclusion criteria: Men and women aged 18 years or older at the time of providing informed consent. Met the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for insomnia disorder: i. nighttime sleep complaints, manifested as difficulty falling asleep, difficulty staying asleep, and / or waking earlier than desired in the morning despite adequate opportunity to sleep; ii. The frequency of complaints is 3 or more times per week; iii. The complaint is more than three months old; iv. Complaints of daytime dysfunction. At screening: Experienced sSOL for ≥30 minutes at least 3 nights per week in the last 4 weeks and / or sWASO for ≥60 minutes at least 3 nights per week in the last 4 weeks. At screening: reported 7-9 hours of regular bedtime (whether asleep or attempting to sleep). At the first screening visit (Visit 1) and second screening visit (Visit 2a): participants reported a regular bedtime between 21:00 and 01:00 (defined as the time when the subject attempts to fall asleep) and a regular wake-up time between 05:00 and 10:00 (defined as the time when the subject gets out of bed that day). -ISI score ≥ 15 at screening and study baseline. At the second screening visit (Visit 2a): Confirmation of current insomnia symptoms, including sSOL ≥ 30 minutes and / or sWASO ≥ 60 minutes on at least 3 out of 7 nights, as determined by sleep diary responses completed on at least 7 consecutive mornings (minimum 5 mornings out of 7 days for eligibility). Second Screening Visit (Visit 2a): Confirmation of regular bedtime and wake-up times, including that the subject had 7-10 hours of regular bedtime (whether asleep or attempting to sleep) as determined by sleep diary responses completed on at least 7 consecutive mornings between the first and second screening visits. Second Screening Visit (Visit 2a): Confirmation of adequate bedtime, such as <7 hours in bed or ≤2 nights longer than 10 hours in bed, as determined by sleep diary responses completed on the mornings of the 7 days between the first and second screening visits. Baseline (Visit 3a): Reconfirmation of insomnia symptoms, including sSOL ≥ 30 minutes on at least 3 of the 7 nights and / or sWASO ≥ 60 minutes on at least 3 of the 7 nights, as determined by sleep diary responses for the last 7 nights of the run-in period. Baseline (Visit 3a): Confirmation of regular bedtime and wake-up times, including that the subject had 7-10 hours of regular bedtime (whether asleep or attempting to sleep) for the last 7 nights of the run-in period. Baseline (Visit 3a): Reconfirmation of regular bedtime (defined as the time the subject attempted to fall asleep) between 21:00 and 01:00 and regular wake-up time (defined as the time the subject got out of bed that day) between 05:00 and 10:00 for the last 7 nights of the run-in period. · Willing and able to comply with all aspects of the protocol, including staying in bed for at least seven hours each night. Subject is unwilling to begin behavioral therapy or other treatment programs for insomnia while participating in this study.

[0455] Exclusion criteria Subjects were not eligible to participate in the study if they met any of the following exclusion criteria: A current diagnosis of sleep-related breathing disorders, including obstructive sleep apnea (with or without continuous positive airway pressure (CPAP) treatment), periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or narcolepsy, or an exclusion score on the SDSB as follows: i. STOPBang score of 5 or greater; ii. an IRLS score of 16 or greater; and iii. ESS score higher than 15 had. -Reported symptoms possibly related to narcolepsy that, in the investigator's clinical opinion, indicated referral for diagnostic evaluation for the presence of narcolepsy. Reported sleep-related violent behavior or sleepwalking or any other complex related behavior, such as making phone calls or preparing and eating meals while asleep. For subjects who have undergone diagnostic polysomnography within one year prior to informed consent: i. Ages 18-64 years: Apnea-hypopnea index greater than 10 or periodic limb movement index with arousal greater than 10. ii. Age 65 or older: Apnea-hypopnea index greater than 15 or periodic limb movements with arousal index greater than 15. Beck Depression Inventory-II (BDI-II) score greater than 19 at screening. Beck Anxiety Inventory (BAI) score greater than 15 at screening. Habitually napped more than three times a week. Women who were nursing or pregnant (as documented by a positive serum beta-human chorionic gonadotropin [β-hCG]) at screening or study baseline. If a negative pregnancy screening test was obtained more than 72 hours before the first dose of study drug, a separate baseline assessment was required. Women who may be pregnant, i. Have had unprotected intercourse within 30 days prior to study enrollment or have not agreed to use highly effective contraceptive methods (e.g., total abstinence, intrauterine device, contraceptive implant, injectable contraceptives, oral contraceptives, or having a vasectomized partner who is documented to be azoospermic) throughout the entire study or for 28 days after discontinuing study drug. Cyclic abstinence methods (e.g., calendar, ovulation, symptomatic temperature, postovulation) and pull-out are not acceptable methods of contraception. ii. Currently abstinent and did not agree to use highly effective methods (as described above) or abstain from sexual activity during the study and for 28 days after discontinuing study drug. iii. Individuals who are currently using hormonal contraception but have not continued a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and who have not agreed to continue using the same contraceptive throughout the study and for 28 days after discontinuing study drug. iv. Note: All women were considered to be of childbearing potential unless they were postmenopausal (defined as having been amenorrheic for at least 12 consecutive months, of the appropriate age group, and were postmenopausal for no other known or suspected cause) or surgically sterilized (i.e., bilateral tubal ligation, hysterectomy, or bilateral oophorectomy, all occurring at least 1 month prior to dosing). In the investigator's opinion, excessive caffeine use or habitual consumption of caffeinated beverages after 6:00 PM contributed to the subject's insomnia and the subject had no intention of stopping caffeine after 6:00 PM during their study participation. Subjects were excluded if, within the previous three months, they had consumed high doses of caffeine (significantly exceeding 250 mg) and had symptoms that would have met the DSM-5 criteria for caffeine intoxication, including five or more of the following symptoms: restlessness, irritability, agitation, insomnia, facial flushing, diuresis, gastrointestinal disturbances, muscle spasms, disorganized thought and speech, tachycardia or cardiac arrhythmia, periods of high energy, or psychomotor agitation. Symptoms that caused distress or impairment in social, occupational, and other forms of functioning and that were not associated with other substances, psychiatric disorders, or medical conditions were excluded. - History of drug or alcohol dependence or abuse within the past two years. Reported a habitual intake of more than 14 alcoholic drinks per week (women) or more than 21 alcoholic drinks per week (men), or were not willing to limit their alcohol intake to two drinks or less per day or to stop drinking within three hours of bedtime during their study participation. -Known to be human immunodeficiency virus (HIV) positive Active viral hepatitis (B or C) as documented by positive serology at screening. Prolongation of the QT / QT interval (QTcF) interval (QTcF>450 milliseconds) corrected by the Fridericia formula, as documented by a repeat ECG at screening (repeated only if the initial ECG showed a QTcF interval>450 milliseconds). At that time, had evidence of clinically significant illness (e.g., cardiac disease; respiratory disease, including chronic obstructive pulmonary disease, acute and / or severe respiratory depression; severe hepatic failure; gastrointestinal disease; renal disease, including severe renal impairment; neurological disease [including subjects lacking capacity and / or whose cognitive decline indicates disorientation to person / place / time and / or situation] or psychiatric disease or malignancy within the past 5 years [excluding adequately treated basal cell carcinoma]) or chronic pain that, in the investigator's opinion, could affect the subject's safety or interfere with study evaluations. Subjects were also excluded if sedatives would have been contraindicated for safety reasons due to their occupation or activity. Concomitant nocturia, which causes frequent need to get out of bed to go to the toilet at night. Any history of medical or psychiatric condition that, in the opinion of the investigator, may have affected the subject's safety or interfered with study evaluations. Any suicidal ideation with intent, with or without a plan, at screening or study baseline or within 6 months of study baseline (i.e., answering "yes" to questions 4 or 5 in the suicidal ideation section of the eC-SSRS). Any suicidal behavior in the past 10 years (according to the suicidal behavior section of the eCSSRS). - Major surgery was scheduled during the study. Use of any prohibited prescription or over-the-counter concomitant medication for 1 week or 5 half-lives, whichever is longer (run-in period), prior to the first dose of study drug. Use of any modality of insomnia treatment, including cognitive behavioral therapy or marijuana, for 1 week or 5 half-lives, whichever is longer (run-in period), prior to the first dose of study medication. Failure of treatment (efficacy or safety) with suvorexant after an adequate dose and sufficient duration of treatment, in the opinion of the investigator. Transmeridian travel across more than three time zones in the 2 weeks prior to screening or between screening and baseline. Positive drug test at screening, induction, or baseline, or unwillingness to abstain from recreational drug use during the study. Hypersensitivity to the study drug or any of the excipients. Currently enrolled in another clinical trial or used any investigational drug or device for 30 days or five half-lives, whichever is longer, prior to informed consent. -Participated in any previous clinical trial of lemborexant.

[0456] Test drug Subjects were administered 5 mg lemborexant tablets, 10 mg lemborexant tablets, or lemborexant-matching placebo tablets.

[0457] [Table 1]

[0458] Study endpoints Primary endpoint The primary endpoint was the mean change from study baseline in subjective sleep onset latency at 6 months.

[0459] Key Secondary Endpoints This study had two key secondary endpoints. The first key secondary endpoint was the mean change from study baseline in subjective sleep efficiency at 6 months. The second key secondary endpoint was the mean change from study baseline in subjective awakenings at 6 months.

[0460] Additional secondary endpoints In addition to the aforementioned study endpoints, the study included several additional secondary endpoints: Mean changes from study baseline in subjective sleep onset latency, subjective sleep efficiency, subjective wake-after-sleep, and subjective total sleep time at treatment initiation (mean of the 7 nights after the first dose in Period 1), 1 month, and 3 months. Mean change from study baseline in subjective total sleep time at 6 months. Change from study baseline in daytime functioning, assessed as the sum score of the four daytime functioning items on the Insomnia Severity Index, at months 1, 3, and 6.

[0461] Safety Endpoints Safety endpoints of the study included (1) the safety and tolerability of lemborexant compared to placebo (during Treatment Period 1) and (2) in subjects exposed to lemborexant for 3, 6, 9, and 12 months.

[0462] result

[0463] [Table 2]

[0464] [Table 3]

[0465] The primary efficacy endpoint was the change from study baseline in mean subjective sleep onset latency (an estimate of the number of minutes it takes a subject to fall asleep from the time they attempt to fall asleep). As shown in Table 2, mean subjective sleep onset was shorter than study baseline for all treatment groups, and subjects treated with lemborexant had shorter subjective sleep onset latency than subjects treated with placebo at equivalent time points. See also Figures 1 and 2.

[0466] [Table 4]

[0467] [Table 5]

[0468] As shown in Table 3, mean subjective sleep efficiency increased relative to study baseline for all treatment groups, with subjects treated with lemborexant experiencing greater increases in subjective sleep efficiency than subjects treated with placebo at equivalent time points. See also Figures 3 and 4.

[0469] [Table 6]

[0470] [Table 7]

[0471] As shown in Table 4, mean subjective awakening onset decreased relative to study baseline in all treatment groups, with subjects treated with lemborexant experiencing greater decreases in mean subjective awakening onset than subjects treated with placebo at equivalent time points. See also Figures 5 and 6.

[0472] [Table 8]

[0473] [Table 9]

[0474] As shown in Table 5, mean subjective total sleep time increased relative to study baseline in all treatment groups, with subjects treated with lemborexant experiencing greater increases in subjective total sleep time than subjects treated with placebo at equivalent time points.

[0475] [Table 10]

[0476] [Table 11]

[0477] [Table 12]

[0478] [Table 13]

[0479] As shown in Tables 6 and 7, mean Insomnia Severity Index scores decreased relative to study baseline for all treatment groups, with subjects treated with lemborexant experiencing greater decreases in Insomnia Severity Index scores than subjects treated with placebo at equivalent time points.

[0480] [Table 14]

[0481] As shown in Table 8, mean scores for items related to sleep quality and morning sleepiness (Insomnia Severity Index) were significantly improved in subjects treated with lemborexant compared to subjects treated with placebo at 6 months.

[0482] [Table 15]

[0483] [Table 16]

[0484] [Table 17]

[0485] Table 11 demonstrates that lemborexant is a safe and well-tolerated drug, as evidenced by the low incidence of adverse events. No deaths were reported during the study.

[0486] Example 2. Treatment of a subject with an insomnia disorder Subjects of both sexes aged 55 years and older were screened for eligibility for treatment. 1006 subjects were randomized to treatment. Demographic information for the subject population is shown in Table 12.

[0487] [Table 18]

[0488] The study consisted of a pre-randomization phase and a randomization phase.

[0489] Pre-randomization phase The pre-randomization phase consisted of three periods: a screening period, a run-in period, and a baseline period.

[0490] Screening Period The screening period began within 35 days prior to randomization. After informed consent was obtained, medical, psychiatric, and sleep history interviews were conducted, including confirmation that the subject met diagnostic criteria for insomnia disorder and reported difficulty staying asleep, early morning awakening, or both. Screening assessments administered included the Insomnia Sleep Index (ISI), Epworth Sleepiness Scale (ESS), STOPBang Sleep Apnea Questionnaire, International Restless Legs Scale (IRLS), and Munich Parasomnia Scale (MUPS). These assessments are collectively referred to as the Sleep Disorder Screening Battery.

[0491] Subjects were given a sleep diary and instructed on how to complete it. After subjects completed the sleep diary every morning for 7 consecutive days, if they were still eligible to participate in the study, they attended a second clinical meeting 10 to 17 days before the randomization phase. Subjects then wore a polysomnograph and received instructions on how to complete the postural stability assessment and cognitive performance assessment battery. Subjects then underwent an 8-hour polysomnography recording. Within 5 minutes of awakening, subjects completed the postural stability assessment and cognitive performance assessment battery.

[0492] If the subject was still eligible to participate, the subject was dispensed a placebo tablet and the run-in period began.

[0493] Implementation period The run-in period began when eligible subjects were dispensed placebo tablets and continued through baseline day 1. During the run-in period, subjects took the placebo within 5 minutes of bedtime each night and remained in bed for at least 7 hours.

[0494] Once the subject had completed the sleep diary entries for at least one consecutive morning during this period, their eligibility was reviewed again. If eligible, the subject returned for the first of two nights during which an overnight polysomnography test would be performed. The Insomnia Severity Index, FSS, and EQ-5D-3L were also assessed. The subject was then administered the study medication within five minutes of their intended bedtime. The subject then underwent an 8-hour polysomnogram. After awakening, a postural and cognitive battery assessment was performed, and a sleep diary was completed. The subject was then free to leave the room for the rest of the day and returned later to repeat the test for another night.

[0495] Subjects were then allowed to go home and take the study medication according to clinic protocols. After a minimum of two nights, the run-in period ended.

[0496] Baseline period On Day 1 of the baseline period, subjects were admitted to the clinic and administered the ISI, FSS, and EQ-5D-3L. For routine safety assessments, blood and urine samples were collected, an ECG was performed, vital signs and weight were assessed, and the eC-SSRS was administered. Subjects who completed the baseline period and continued to meet the eligibility criteria were randomized, and the randomization phase began.

[0497] Randomization Phase The randomization phase consisted of a treatment period and a follow-up period.

[0498] Treatment duration The treatment period lasted 31 days. Subjects were randomized in a double-blind manner to receive placebo, tablets containing 5 mg of lemborexant, tablets containing 10 mg of lemborexant, or tablets containing 6.25 mg of zolpidem ER.

[0499] The study drug was administered within 5 minutes of the subject's average habitual bedtime, and overnight polysomnography recording was initiated. The following morning (Day 2), at the completion of recording, postural stability and cognitive performance were assessed. The subject returned on the evening of Day 2, and a blood sample was taken before administration of the study drug, which was then administered within 5 minutes of the subject's average habitual bedtime. Polysomnography recording was again initiated. The following morning (Day 3), postural stability and cognitive performance were assessed. A blood sample was also taken.

[0500] Subjects then completed their own sleep diaries. The eC-SSRS was administered. Within 1.5 hours of waking, subjects rated their level of sleepiness that morning. If clinicians deemed the subject safe to be discharged, they were allowed to leave the hospital.

[0501] After returning home, subjects took the study medication before bedtime each night and completed the sleep diary within one hour of waking up.

[0502] On Day 29, subjects returned to the clinic. Study medication was administered within 5 minutes of the subjects' average habitual bedtime, and polysomnography was performed. The following morning (Day 30), postural stability and cognitive performance were assessed. 1.5 hours after awakening, subjects rated their level of sleepiness that morning.

[0503] Subjects returned to the clinic on the evening of Day 30. A pre-dose blood sample was taken, and the study drug was again administered within 5 minutes of the subject's average habitual bedtime. Polysomnography was initiated. The following morning (Day 31), postural stability and cognitive performance were assessed, and blood samples were taken. The ISI, FSS, EQ-5D-3L, and PGI-Insomnia were administered. Blood and urine samples were taken for routine safety assessments. An electrocardiogram was performed, and vital signs and weight were assessed. Subjects then completed the eC-SSRS. One and a half hours after their wake-up time, subjects rated their level of sleepiness that morning.

[0504] Follow-up period The follow-up period began when subjects were discharged from the hospital at the end of the treatment period. Subjects stopped taking the study medication but continued to complete their sleep diaries each morning until the end of the study visit.

[0505] Fourteen to 18 days after completing the treatment period, subjects returned for an end-of-study visit. The T-BWSQ and eC-SSRS were administered, and routine safety assessments were performed.

[0506] Research interruption Subjects who discontinued study medication prematurely were to return as soon as practicable after discontinuation. If a subject discontinued due to an adverse event, the adverse event had to be followed until resolution or for 2 weeks, whichever occurred first. In addition, subjects who discontinued prematurely underwent a urine drug test.

[0507] Test drug Subjects received two tablets daily according to the treatment group to which they were randomized: 5 mg lemborexant treatment group: One zolpidem ER-matched placebo tablet and one lemborexant 5 mg tablet. 10 mg lemborexant treatment group: One zolpidem ER-matched placebo tablet and one lemborexant 10 mg tablet. Zolpidem ER 6.25 mg: One zolpidem ER 6.25 mg tablet and one lemborexant matching placebo tablet. Placebo: One zolpidem ER matching placebo tablet and one lemborexant matching placebo tablet.

[0508] Study endpoints The study had a primary endpoint, several important secondary endpoints, and several additional secondary endpoints.

[0509] Primary endpoint The primary endpoint was to determine the change from baseline in mean latency to persistent sleep at days 29 and 30 for lemborexant 5 mg or 10 mg compared to placebo.

[0510] Key Secondary Endpoints One key secondary endpoint was to determine the change from baseline in mean sleep efficiency at 29 and 30 days after treatment with 5 mg or 10 mg lemborexant compared to placebo.

[0511] Another key secondary endpoint was to determine the change from baseline in mean wake onset scores at 29 and 30 days after treatment with 5 mg or 10 mg lemborexant compared to placebo.

[0512] Another key secondary endpoint was to determine the change from baseline in mean wake after sleep onset in the second half of the night on days 29 and 30 following treatment with 5 mg or 10 mg lemborexant compared with 6.25 mg zolpidem ER.

[0513] Exemplary additional secondary endpoints are the change from baseline in mean body sway units on the Postural Stability Test on days 2 and 3 following administration of 5 mg or 10 mg of lemborexant compared to zolpidem.

[0514] Inclusion criteria Subjects were eligible to participate in the study if they met all of the following inclusion criteria: Men aged 65 years or older or women aged 55 years or older at the time of informed consent. Met the criteria for insomnia disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: i. Nighttime sleep complaints, manifested as difficulty staying asleep and / or waking earlier than desired in the morning despite ample opportunity to sleep. ii. The frequency of the complaint is 3 or more times per week. iii. The complaint is filed for more than three months. iv. Complaints of daytime dysfunction. At screening: Experienced sWASO, typically lasting 60 minutes or more, at least 3 nights per week in the last 4 weeks. At screening: reported 7-9 hours of regular bedtime (whether asleep or attempting to sleep). At screening, subjects reported a habitual bedtime between 21:00 and 24:00 (defined as the time at which they attempted to fall asleep) and a habitual wake-up time between 05:00 and 09:00. At screening and during the admission procedure before the first polysomnogram during the run-in period: ISI score ≥ 13. Confirmation of current insomnia symptoms, such as sWASO ≥ 60 minutes on at least 3 of the 7 nights, as determined by sleep diary responses for the mornings of the 7 days immediately preceding the second screening visit (minimum 5 of the 7 days required for eligibility). Confirmation of regular bedtimes and wake-up times, such that on no more than two nights, either bedtime (defined as the time the subject attempted to fall asleep) or wake-up time (defined as the time the subject got out of bed that day) deviated by more than one hour from the mean habitual bedtime or median habitual wake-up time, respectively, calculated from the screening sleep diary entries, as determined from morning sleep diary responses during the 7 days immediately preceding the second screening visit. - Confirmation that the patient's bedtime duration is sufficient, such as having no more than 2 nights in bed lasting less than 7 hours or more than 10 hours, as determined from the responses to the morning sleep diary during the 7 days immediately prior to the second screening visit. During the run-in period: Reconfirmation of insomnia symptoms, such as sWASO of 60 minutes or more on at least 3 out of 7 nights, as determined by responses to the morning sleep diary during the 7 days immediately prior to the first polysomnogram during the run-in period. During the induction period: Reaffirmation of regular bedtimes and wake-up times as defined above. During the induction period: Reconfirmation of sufficient bedtime as defined above. During the run-in period: Objective evidence of insomnia by polysomnography as follows: mean WASO on two consecutive polysomnograms of 60 minutes or more, with no less than 45 minutes on either night. · Willing and able to comply with all aspects of the protocol, including staying in bed for at least seven hours each night. Subject is unwilling to begin behavioral therapy or other treatment programs for insomnia while participating in this study.

[0515] Exclusion criteria Subjects were not eligible to participate in the study if they met any of the following exclusion criteria: A current exclusion score on a screening instrument that excludes individuals with a diagnosis of sleep-related breathing disorder (including obstructive sleep apnea with or without continuous positive airway pressure treatment), periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or narcolepsy, or symptoms of certain sleep disorders other than insomnia, as follows: i. STOPBang Sleep Apnea Questionnaire score of 5 or greater ii. IRLS score of 16 or above iii. ESS score higher than 15 (a score of 11-15 requires excessive daytime sleepiness documented in the subject's medical history) had. -Reported symptoms possibly related to narcolepsy that, in the investigator's clinical opinion, indicated referral for diagnostic evaluation for the presence of narcolepsy. An item on the MUPS corresponding to a history of sleepwalking disorder was endorsed, or a history of sleep-related violent behavior, sleepwalking disorder, or another parasomnia condition that, in the investigator's opinion, made the subject unsuitable for the study was reported. Apnea-hypopnea index greater than 15 or periodic limb movements with arousals index greater than 15 as measured by PSG at the second screening visit. Beck Depression Inventory-II (BDI-II) score greater than 19 at screening. Beck Anxiety Inventory (BAI) score greater than 15 at screening. Habitually taking daytime naps more than three times a week. Were female of childbearing potential. (Note: All women were considered of childbearing potential unless they were postmenopausal (defined as amenorrhea for at least 12 consecutive months, of the appropriate age group, and postmenopausal for no other known or suspected cause) or surgically sterilized (i.e., bilateral tubal ligation, hysterectomy, or bilateral oophorectomy, all at least 1 month prior to treatment). In the investigator's opinion, excessive caffeine use or habitual consumption of caffeinated beverages after 6:00 PM contributed to the subject's insomnia, and the subject had no intention of stopping caffeine after 6:00 PM during his or her participation in the study. - History of drug or alcohol dependence or abuse within the past two years. Reported habitual consumption of more than 14 alcohol-containing drinks per week (women) or more than 21 alcohol-containing drinks per week (men), or habitually consumed alcohol within three hours before bedtime and were not willing to limit their alcohol intake to two drinks or less per day or to stop drinking within three hours before bedtime during their study participation. -Known to be human immunodeficiency virus positive. Active viral hepatitis (B or C) as documented by positive serology at screening. Prolongation of the QT / QT interval (QTcF) interval (QTcf>450 msec) corrected for heart rate by the Fridericia formula, as demonstrated by a repeat ECG at screening (repeated only if the initial ECG showed a QTcf interval>450 msec). At that time, the subject had evidence of clinically significant illness (e.g., cardiac disease; respiratory disease, including chronic obstructive pulmonary disease, acute and / or severe respiratory depression; gastrointestinal disease, including severe hepatic dysfunction; renal disease, including severe renal dysfunction; neurological disease, including myasthenia gravis; psychiatric disease; malignancy within the past 5 years other than adequately treated basal cell carcinoma) or chronic pain that, in the investigator's opinion, could have affected the subject's safety or interfered with study assessments, including their ability to perform cognitive PAB tasks. Subjects were also excluded if sedatives would have been contraindicated for safety reasons due to their occupation or activity. Concomitant nocturia, which causes frequent need to get out of bed to go to the toilet at night. Any history of medical or psychiatric condition that, in the opinion of the investigator, could have affected the subject's safety or interfered with study evaluations, including their ability to perform the PAB. Any suicidal ideation with or without a plan at the time of or within 6 months prior to administration of the eC-SSRS in the pre-randomization phase (i.e., answering "yes" to questions 4 or 5 in the suicidal ideation section of the eC-SSRS). Any suicidal behavior in the past 10 years (according to the suicidal behavior section of the eC-SSRS). - Major surgery was scheduled during the study. Use of any prohibited prescription or over-the-counter concomitant medication for 1 week or 5 half-lives, whichever is longer (run-in period), prior to the first dose of study drug. Use of any modality of insomnia treatment, including cognitive behavioral therapy or marijuana, for 1 week or 5 half-lives, whichever is longer (run-in period), prior to the first dose of study medication. Failure of treatment (efficacy or safety) with suvorexant after an adequate dose and sufficient duration of treatment, in the opinion of the investigator. Transmeridian travel across more than three time zones in the two weeks prior to screening or between screening and baseline, or planned travel across more than three time zones during the study. had a positive drug test at screening, induction, or baseline, or was unwilling to abstain from recreational drug use during the study. Hypersensitivity to the study drug (lemborexant or zolpidem) or its excipients. Currently enrolled in another clinical trial or used any investigational drug or device for 30 days or five half-lives, whichever is longer, prior to informed consent. -Participated in any previous clinical trial of lemborexant.

[0516] result

[0517] [Table 19]

[0518] [Table 20]

[0519] As shown in Table 13, mean persistent sleep latency was reduced for all lemborexant treatment groups relative to baseline, placebo, and zolpidem.

[0520] [Table 21]

[0521] [Table 22]

[0522] As shown in Table 14, mean sleep efficiency increased for all lemborexant treatment groups relative to baseline, placebo, and zolpidem treatment groups.

[0523] [Table 23]

[0524] [Table 24]

[0525] As shown in Table 15, mean awakenings after sleep onset were reduced in all lemborexant treatment groups relative to baseline, placebo, and zolpidem treatment groups.

[0526] [Table 25]

[0527] [Table 26]

[0528] As shown in Table 16, mean awakenings during the second half of the night were reduced in all lemborexant treatment groups compared to baseline, placebo, and zolpidem treatment groups.

[0529] [Table 27]

[0530] [Table 28]

[0531] As shown in Table 17, mean total sleep time increased for all lemborexant treatment groups relative to baseline, placebo, and zolpidem treatment groups.

[0532] [Table 29]

[0533] As shown in Table 18, mean subjective sleep onset latency was reduced for all lemborexant treatment groups relative to baseline, placebo, and zolpidem treatment groups.

[0534] [Table 30]

[0535] As shown in Table 19, mean subjective sleep efficiency increased for the 10 mg lemborexant treatment groups relative to baseline, the placebo treatment group, and the zolpidem treatment group.

[0536] [Table 31]

[0537] As shown in Table 20, mean subjective awakening after sleep onset was reduced in the 10 mg lemborexant treatment groups compared to baseline, the placebo treatment group, and the zolpidem treatment group.

[0538] [Table 32]

[0539] As shown in Table 21, mean subjective total wakefulness time increased for the 10 mg lemborexant treatment groups relative to baseline, placebo treatment, and zolpidem treatment groups.

[0540] [Table 33]

[0541] As shown in Table 22, mean Insomnia Severity Index total scores decreased in the lemborexant treatment groups compared to baseline and the placebo treatment groups.

[0542] [Table 34]

[0543] As shown in Table 23, mean Insomnia Severity Index daytime scores decreased in the lemborexant treatment groups compared to baseline and the placebo treatment group.

[0544] [Table 35]

[0545] [Table 36]

[0546] As shown in Table 24, body sway was reduced in all lemborexant treatment groups relative to baseline, placebo, and zolpidem treatment groups. Lemborexant had no significant effect on postural stability compared to placebo.

[0547] [Table 37]

[0548] [Table 38]

[0549] [Table 39]

[0550] As shown in Table 27, administration of lemborexant did not interfere with the subjects' ability to be awakened by external stimuli.

[0551] [Table 40]

[0552] As shown in Table 28, treatment with lemborexant (both doses) resulted in a greater reduction in sleep re-onset latency than treatment with placebo and zolpidem.

[0553] [Table 41]

[0554] Table 29 demonstrates that lemborexant is a safe and well-tolerated drug, as evidenced by the low incidence of adverse events. No deaths were reported during the study.

[0555] Figures 11A-11D show that after the first two nights of treatment, treatment with zolpidem ER significantly worsened performance on 3 of 4 domains of the Cognitive Performance Assessment Battery compared to placebo and 5 mg treatment, and 2 of 4 domains compared to 10 mg lemborexant. In contrast, neither dose of lemborexant was different from placebo at any time point on cognitive testing.

[0556] Figure 12 shows that treatment with lemborexant (both doses) resulted in a greater reduction in the length of prolonged wakefulness compared to placebo than treatment with zolpidem ER.

[0557] Figure 15 shows that treatment with lemborexant (both doses) significantly increased non-REM sleep compared to treatment with placebo and zolpidem ER.

[0558] Figure 16 shows that treatment with lemborexant (both doses) significantly reduced mean REM latency compared to treatment with placebo and zolpidem ER.

[0559] Example 3. Responder Analysis of Treatment of Subjects with Insomnia Disorder The data collected in the studies described in Examples 1 and 2 were pooled and the response of each subject was analyzed.

[0560] Subjective sleep onset latency

[0561] [Table 42]

[0562] As shown in Table 30, at the start of treatment (first 7 days) and at the end of month 1, the proportion of responders (defined as subjects with an sSOL of 20 minutes or less, provided their baseline sSOL was at least 30 minutes) was statistically significantly superior to placebo treatment for both lemborexant doses.

[0563] [Table 43]

[0564] As shown in Table 31, at the start of treatment (first 7 days) and at the end of month 1, the proportion of responders (defined as those with an sWASO of ≤60 minutes and a decrease of at least 10 minutes from baseline, provided that baseline sWASO was >60 minutes) was statistically significantly superior to placebo treatment for both lemborexant doses.

[0565] Insomnia Severity Index

[0566] [Table 44]

[0567] [Table 45]

[0568] Table 32 provides a summary and analysis of responders, defined as subjects whose ISI total score decreased by 7 or more points compared to baseline at the end of Month 1. Table 33 provides a summary and analysis of responders, defined as subjects whose ISI total score decreased compared to baseline and was less than 10 at Month 1. For both doses of lemborexant, the difference in responder rates between the lemborexant and placebo groups was statistically significant.

[0569] As shown in Table 32, at the end of Month 1, the proportion of subjects with a 7-point or greater reduction in ISI total score was 33.6% in the placebo group, compared to 47.3% in the 5 mg lemborexant treatment group and 47.8% in the 10 mg lemborexant treatment group.

[0570] As shown in Table 33, at the end of Month 1, the proportion of subjects whose ISI total score decreased to <10 at Month 1 was 20.3% in the placebo group, compared to 33.0% in the 5 mg lemborexant group and 33.4% in the 10 mg lemborexant group.

Claims

1. 1. A method for reducing subjective sleep onset latency (sSOL) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the sSOL is reduced relative to baseline for at least one month.

2. 10. The method of claim 1, wherein the sSOL is decreased relative to baseline for at least 6 months.

3. 10. The method of claim 1, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least one month.

4. 3. The method of claim 2, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least six months.

5. 10. The method of claim 1, wherein the sSOL is reduced by at least 20 minutes.

6. 10. The method of claim 1, wherein the sSOL is 40 minutes or less.

7. 7. The method of claim 6, wherein the sSOL is 25 minutes or less.

8. The method of claim 1 , wherein the subject has insomnia.

9. 1. A method for improving subjective sleep efficiency (sSE) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the sSE is increased relative to baseline for at least one month.

10. 10. The method of claim 9, wherein the sSE is increased over at least 6 months relative to baseline.

11. 10. The method of claim 9, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least one month.

12. 11. The method of claim 10, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least six months.

13. 10. The method of claim 9, wherein the sSE is improved by at least 13%.

14. 10. The method of claim 9, wherein the subject has insomnia.

15. 1. A method for reducing subjective wakefulness after the first dose of sodium iodide (sWASO) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the sWASO is reduced relative to baseline for at least one month.

16. 16. The method of claim 15, wherein the sWASO is reduced relative to baseline for at least 6 months.

17. 16. The method of claim 15, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least one month.

18. 17. The method of claim 16, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least six months.

19. 16. The method of claim 15, wherein the sWASO is reduced by at least 40 minutes.

20. 16. The method of claim 15, wherein the subject has insomnia.

21. 1. A method for identifying a subject responsive to treatment with lemborexant or a pharmaceutically acceptable salt thereof, comprising: a) determining the subject's pre-treatment subjective wake-after-start score (sWASO); b) if the pre-treatment period sWASO is greater than or equal to 60 minutes, administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, for a treatment period; c) determining the subject's sWASO after the treatment period; d) if the post-treatment period sWASO is less than 60 minutes and is at least 10 minutes shorter than the pre-treatment period sWASO, administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof. A method comprising:

22. 22. The method of claim 21, wherein the post-treatment period sWASO is at least 20 minutes shorter than the pre-treatment period sWASO.

23. 22. The method of claim 21, wherein the post-treatment period sWASO is at least 30 minutes shorter than the pre-treatment period sWASO.

24. 22. The method of claim 21, wherein a pre-treatment period subjective sleep efficiency (sSE) is determined prior to administering lemborexant or a pharmaceutically acceptable salt thereof.

25. 25. The method of claim 24, wherein sSE is determined after a treatment period following administration of lemborexant or a pharmaceutically acceptable salt thereof.

26. 26. The method of claim 25, wherein the post-treatment period sSE is improved by at least 10% relative to the pre-treatment period sSE.

27. 26. The method of claim 25, wherein the post-treatment period sSE is improved by at least 14% relative to the pre-treatment period sSE.

28. 22. The method of claim 21, wherein a pre-treatment period subjective sleep onset latency (sSOL) is determined prior to administering lemborexant or a pharmaceutically acceptable salt thereof.

29. 29. The method of claim 28, wherein sSOL is determined after a treatment period following administration of lemborexant or a pharmaceutically acceptable salt thereof.

30. 30. The method of claim 29, wherein the post-treatment period sSOL is at least 15 minutes shorter than the pre-treatment period sSOL.

31. 30. The method of claim 29, wherein the post-treatment period sSOL is at least 20 minutes shorter than the pre-treatment period sSOL.

32. A method for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving a sustained reduction in time to sleep onset as measured by subjective sleep onset latency (sSOL) compared to placebo over at least one month of treatment.

33. A method for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving a sustained reduction in time to sleep onset as measured by subjective sleep onset latency (sSOL) compared to placebo through six months of treatment.

34. A method for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for at least one month, and wherein the dosage form is achievable in terms of maintaining a reduction in time to sleep onset as measured by subjective sleep onset latency (sSOL) compared to placebo over at least one month of treatment.

35. A method for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form may be administered to a patient for six months, and wherein the dosage form is achievable in terms of maintaining a reduction in time to fall asleep as measured by subjective sleep onset latency (sSOL) compared to placebo throughout six months of treatment.

36. A method for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvement in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo over at least one month of treatment.

37. A method for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvements in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo through six months of treatment.

38. A method for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for at least one month, and wherein the dosage form is capable of maintaining an improvement in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo over at least one month of treatment.

39. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for six months, and wherein the dosage form is capable of maintaining an improvement in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo throughout six months of treatment.

40. A method for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvement in wake after sleep onset (sWASO) compared to placebo over at least one month of treatment.

41. A method for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is capable of achieving sustained improvement in wake after sleep onset (sWASO) compared to placebo through six months of treatment.

42. A method for treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for at least one month, and wherein the dosage form is capable of achieving sustained improvement in wake after sleep onset (sWASO) compared to placebo over at least one month of treatment.

43. A method of treating insomnia, comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose ranging from about 5 to 10 mg, wherein the dosage form can be administered to a patient for six months, and the dosage form is capable of achieving sustained improvement in wake after sleep onset (sWASO) compared to placebo throughout six months of treatment.

44. 1. A method for treating insomnia in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep onset latency is reduced relative to baseline for at least one month.

45. 1. A method of treating insomnia in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant, or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep efficiency is increased relative to baseline for at least one month.

46. 1. A method of treating insomnia in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective awakenings after sleep onset are reduced relative to baseline for at least one month.

47. 1. A method of treating insomnia comprising orally administering a dosage form containing 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to a patient no more than once per night and within minutes of going to bed, with at least 7 hours remaining until the patient's planned wake-up time, wherein if the 5 mg dose is well tolerated but not effective, the dose may thereafter be increased to 10 mg once daily; the dosage form is achievable with respect to maintaining a reduction in time to sleep onset in subjective sleep onset latency (sSOL) over at least one month of treatment; The method wherein said sSOL is decreased relative to baseline by at least 15 minutes.

48. 1. A method of treating insomnia comprising orally administering a dosage form containing 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to a patient no more than once per night and within minutes of going to bed, with at least 7 hours remaining until the patient's planned wake-up time, wherein if the 5 mg dose is well tolerated but not effective, the dose may thereafter be increased to 10 mg once daily; the dosage form is achievable with respect to maintaining an improvement in sleep efficiency in subjective sleep efficiency (sSE) over at least one month of treatment; The method, wherein the sSE is improved by at least 4% over baseline.

49. 1. A method of treating insomnia comprising orally administering a dosage form containing 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to a patient no more than once per night and within minutes of going to bed, with at least 7 hours remaining until the patient's planned wake-up time, wherein if the 5 mg dose is well tolerated but not effective, the dose may thereafter be increased to 10 mg once daily; The dosage form is achievable with respect to maintaining an improvement in subjective wakefulness after onset (sWASO) over at least one month of treatment; wherein the sWASO is reduced by at least 29 minutes relative to baseline.

50. 1. A method of treating insomnia comprising orally administering a dosage form containing 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering orally the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night immediately prior to going to bed with at least 7 hours remaining until the patient's planned wake-up time; The dose may be increased to 10 mg based on clinical response and tolerability; The dosage form is achievable in terms of maintaining a reduction in time to sleep onset as measured by subjective sleep onset latency (sSOL) over at least one month of treatment.

51. 51. The method of claim 50, wherein the dosage form is achievable with respect to maintaining a reduction in time to sleep onset in subjective sleep onset latency (sSOL) over at least six months of treatment.

52. 51. The method of claim 50, wherein the dosage form can be administered to the patient for at least one month.

53. 51. The method of claim 50, wherein the dosage form can be administered to the patient for at least six months.

54. 51. The method of claim 50, wherein the sSOL is decreased relative to baseline by at least 15 minutes.

55. 1. A method of treating insomnia comprising orally administering a dosage form containing 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, administering orally the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night immediately prior to going to bed with at least 7 hours remaining until the patient's planned wake-up time; The dose may be increased to 10 mg based on clinical response and tolerability; The dosage form is achievable in terms of maintaining improvements in sleep efficiency in subjective sleep efficiency (sSE) over at least one month of treatment.

56. 56. The method of claim 55, wherein the dosage form is achievable in terms of maintaining improvements in sleep efficiency in subjective sleep efficiency (sSE) over at least six months of treatment.

57. 56. The method of claim 55, wherein the dosage form can be administered to the patient for at least one month.

58. 56. The method of claim 55, wherein the dosage form can be administered to the patient for at least six months.

59. 56. The method of claim 55, wherein the sSE is improved by at least 4% over baseline.

60. 1. A method of treating insomnia comprising orally administering a dosage form containing 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, orally administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night immediately prior to going to bed with at least 7 hours remaining until the patient's planned wake-up time, which dose may be increased to 10 mg based on clinical response and tolerability; The dosage form is achievable in terms of maintaining an improvement in subjective wakefulness after onset (sWASO) over at least one month of treatment.

61. 61. The method of claim 60, wherein the dosage form is achievable in terms of maintaining an improvement in subjective wakefulness after onset (sWASO) over at least six months of treatment.

62. 61. The method of claim 60, wherein the dosage form can be administered to the patient for at least one month.

63. 61. The method of claim 60, wherein the dosage form can be administered to the patient for at least six months.

64. 61. The method of claim 60, wherein the sWASO is reduced by at least 29 minutes relative to baseline.

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