JP2022538170A - Lemborexant for treating sleep problems - Google Patents

Abstract

A method of improving subjective sleep efficiency, reducing subjective sleep onset latency and/or reducing subjective nocturnal awakenings in a subject, wherein the subject is administered 5 mg or 10 mg lemborexant or an equivalent dose thereof. Disclosed herein are methods comprising administering a biologically acceptable salt. As used herein, improving a subject's subjective sleep efficiency comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, reducing subjective sleep onset latency to Also disclosed is lemborexant or a pharmaceutically acceptable salt thereof for use in reducing and/or reducing subjective wakefulness. [Selection figure] None

Description

Disclosed herein are novel methods and uses of lemborexant to improve sleep parameters such as subjective sleep efficiency, decrease subjective sleep onset latency, and/or decrease subjective nocturnal awakenings.

Sleep disorders such as insomnia are characterized by difficulty falling asleep, staying asleep or waking early in the morning, with 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 melatonergic agents, antihistamines and other prescription and non-prescription drugs with sedative properties.

The orexin neuropeptides (orexin A and orexin B) are recognized as critical upstream regulators of many wake-promoting neurotransmitters through two G protein-coupled receptors, the orexin-1 and orexin-2 receptors. ing. More recently, antagonizing orexin receptors, particularly both orexin receptors, by small molecules has emerged as an alternative approach to treating sleep problems. There remains an unmet medical need for safe and effective therapeutics that are conveniently administered to combat insomnia.

Lemborexant, also known as E2006, is a dual orexin receptor antagonist. It has been studied in clinical trials and found to have advantageous properties, such as wakefulness, reduced sleep onset latency and/or improved sleep efficiency.

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

In some embodiments, provided herein is a method of improving subjective sleep efficiency (sSE) in a subject, comprising administering to the subject 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof. wherein the sSE is increased over baseline for at least 1 month.

In some embodiments, provided herein is a method of reducing subjective wakefulness (sWASO) in a subject, comprising administering to the subject 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof. wherein sWASO is reduced over baseline for at least 1 month.

In some embodiments, provided herein is a method of identifying a subject responsive to treatment with lemborexant or a pharmaceutically acceptable salt thereof, comprising: (a) subjectively midway through the subject's treatment period; Determining wakefulness (sWASO); (b) if the sWASO prior to the treatment period is greater than or equal to 60 minutes, administer 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof over the treatment period to the subject. (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 at least 10 minutes less than the pre-treatment period sWASO, A method is disclosed comprising administering to a subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof.

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg orally administering the dosage form, wherein the dosage form achieved in terms of maintaining a reduction in time to sleep onset in subjective sleep latency (sSOL) compared to placebo during treatment for at least 1 month A method is disclosed that is possible.

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg orally administering the dosage form, wherein the dosage form achieved in terms of maintaining a reduction in time to sleep onset in subjective sleep latency (sSOL) compared to placebo during treatment through 6 months A method is disclosed that is possible.

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg comprising orally administering the dosage form, wherein the dosage form can be administered to the patient for at least one month, wherein the dosage form improves subjective sleep onset latency ( Methods are disclosed that are achievable with respect to maintaining a reduction in time to sleep onset in sSOL).

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg comprising administering the dosage form orally, the dosage form can be administered to the patient over a period of 6 months, the dosage form improving subjective sleep onset latency (sSOL ) is achievable with respect to maintaining a reduction in time to sleep onset.

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg comprising orally administering the dosage form, wherein the dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) compared to placebo during treatment for at least one month. , a method is disclosed.

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg comprising orally administering the dosage form, wherein the dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) compared to placebo during treatment through 6 months , a method is disclosed.

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg comprising orally administering the dosage form, wherein the dosage form can be administered to the patient for at least one month, wherein the dosage form improves subjective sleep efficiency (sSE A method is disclosed that is achievable with respect to maintaining improved sleep efficiency in ).

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg comprising administering the dosage form orally, wherein the dosage form can be administered to the patient over a period of 6 months, wherein the dosage form improves subjective sleep efficiency (sSE) compared to placebo during treatment through 6 months A method is disclosed that is achievable with respect to maintaining improved sleep efficiency in

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg Disclosed are methods comprising orally administering a dosage form, wherein the dosage form is achievable with respect to maintaining improvement in wakefulness after sleep disturbance (sWASO) compared to placebo during treatment for at least one month. be.

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg A method is disclosed comprising orally administering a dosage form, wherein the dosage form is achievable with respect to maintaining improvement in wake on wakefulness (sWASO) compared to placebo during treatment through 6 months. be.

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg comprising orally administering the dosage form, wherein the dosage form can be administered to the patient for at least one month, and wherein the dosage form has an increase in wakefulness after sleep disturbance (sWASO) compared to placebo during treatment for at least one month; Methods are disclosed that are achievable with respect to sustaining improvements.

In some embodiments, provided herein are methods of treating insomnia, comprising lemborexant, or a pharmaceutically acceptable salt thereof, in a single daily dose in the range of about 5-10 mg comprising administering the dosage form orally, wherein the dosage form can be administered to a patient over a period of 6 months, wherein the dosage form improves wake after awakening (sWASO) compared to placebo during treatment through 6 months A method is disclosed that is achievable with respect to maintaining .

In some embodiments, provided herein are methods 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. A method is disclosed, comprising: subjective sleep onset latency is decreased relative to baseline for at least one month.

In some embodiments, provided herein are methods 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. A method is disclosed, comprising: subjective sleep efficiency increases relative to baseline for at least one month.

In some embodiments, provided herein are methods 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. Disclosed are methods comprising: subjective mid-arousal is reduced relative to baseline for at least one month.

In some embodiments, described herein, a method of treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof wherein the method involves administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to the patient no more than once per night and several minutes before bedtime, with at least 7 hours remaining until the scheduled wake-up time. If the 5 mg dose is well tolerated but is not effective, then the dose can be increased to 10 mg once daily and the dosage form maintained for at least 1 month. Achievable during treatment with respect to maintaining a reduction in time to sleep onset in subjective sleep onset latency (sSOL), where sSOL is reduced by at least 15 minutes relative to baseline.

In some embodiments, described herein, a method of treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof wherein the method includes administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to the patient orally no more than once per night, immediately prior to bedtime, with at least 7 hours remaining until the scheduled wake-up time. The daily dose may be increased to 10 mg based on clinical response and tolerability, and the dosage form is maintained until sleep onset at subjective sleep onset latency (sSOL) during treatment for at least 1 month. , and sSOL is reduced by at least 15 minutes relative to baseline.

In some embodiments, described herein, a method of treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof wherein the method involves administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to the patient no more than once per night and several minutes before bedtime, with at least 7 hours remaining until the scheduled wake-up time. If the 5 mg dose is well tolerated but is not effective, then the dose can be increased to 10 mg once daily and the dosage form maintained for at least 1 month. Achievable in terms of maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) during treatment, where sSE is improved by at least 4% over baseline.

In some embodiments, described herein, a method of treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof wherein the method includes administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to the patient orally no more than once per night, immediately prior to bedtime, with at least 7 hours remaining until the scheduled wake-up time. The daily dose may be increased to 10 mg based on clinical response and tolerability, and the dosage form is expected to improve sleep efficiency in subjective sleep efficiency (sSE) during treatment for at least one month. Achievable in terms of sustaining improvement, sSE is improved by at least 4% over baseline.

In some embodiments, described herein, a method of treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof wherein the method involves administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to the patient no more than once per night and several minutes before bedtime, with at least 7 hours remaining until the scheduled wake-up time. If the 5 mg dose is well tolerated but is not effective, then the dose can be increased to 10 mg once daily and the dosage form maintained for at least 1 month. Maintaining improvement in subjective wakefulness (sWASO) during treatment is achievable, with sWASO decreasing by at least 29 minutes versus baseline.

In some embodiments, described herein, a method of treating insomnia comprising orally administering a dosage form comprising 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof wherein the method includes administering a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to the patient orally no more than once per night, immediately prior to bedtime, with at least 7 hours remaining until the scheduled wake-up time. The daily dose may be increased to 10 mg based on clinical response and tolerability, and the dosage form maintains improvement in subjective wakefulness after treatment (sWASO) for at least 1 month and sWASO is reduced by at least 29 minutes versus baseline.

In some embodiments, provided herein is a method of treating insomnia characterized by difficulty falling asleep and/or staying asleep, with or without concomitant impairment of daily functioning, comprising administering 5 mg or A method is disclosed comprising administering 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof.

In some embodiments, administration of lemborexant or a pharmaceutically acceptable salt thereof does not significantly affect postural stability of subjects relative to placebo.

Figure 3 shows the change from baseline in the median first and third quartile of time as a function of treatment duration for subjective sleep onset latency in patients treated with placebo, 5 mg lemborexant or 10 mg lemborexant. . Median time first and third quartiles are presented as a function of treatment duration for subjective sleep onset latency in patients treated with placebo, 5 mg lemborexant or 10 mg lemborexant. Figure 2 shows the change from baseline in sleep efficiency percentage (least squares mean) as a function of treatment duration for subjective sleep efficiency in patients treated with placebo, 5 mg lemborexant or 10 mg lemborexant. Mean sleep efficiency percentages are presented as a function of treatment duration for subjective sleep efficiency in patients treated with placebo, 5 mg lemborexant, or 10 mg lemborexant. FIG. 1 shows the change from baseline in median time (least squares mean) for subjective nocturnal awakening in patients treated with placebo, 5 mg lemborexant or 10 mg lemborexant as a function of treatment duration. Mean time for subjective nocturnal awakening in patients treated with placebo, 5 mg lemborexant or 10 mg lemborexant is shown as a function of treatment duration. Treatment change from baseline in median time 1st and 3rd quartile for sustained sleep latency in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant or 10 mg lemborexant Shown as a function of time. Shown are model estimates of the 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. Model estimates of the change from baseline in time to wake after waking in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant are shown as a function of treatment duration. Model estimates of the change from baseline in late night nocturnal wake times as a function of treatment duration are shown for patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant. Change from baseline in the four domains of the Cognitive Performance Assessment Battery on Days 2/3 and 30/31 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant ( least squares mean). Change from baseline in the four domains of the Cognitive Performance Assessment Battery on Days 2/3 and 30/31 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant ( least squares mean). Change from baseline in the four domains of the Cognitive Performance Assessment Battery on Days 2/3 and 30/31 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant ( least squares mean). Change from baseline in the four domains of the Cognitive Performance Assessment Battery on Days 2/3 and 30/31 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant ( least squares mean). Prolonged wakefulness duration (≥5 minutes while trying to sleep) on days 2/3 and 30/31 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant or 10 mg lemborexant (defined as the duration of wakefulness following) fractional change from baseline (least squares mean). Stage N1, Stage N2 and Stage N3 on nights of Day 1/2 and Days 29/30 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant or 10 mg lemborexant, respectively Shows the change (least squares mean) from baseline in fractions in sleep during sleep. Stage N1, Stage N2 and Stage N3 on nights of Day 1/2 and Days 29/30 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant or 10 mg lemborexant, respectively Shows the change (least squares mean) from baseline in fractions in sleep during sleep. Stage N1, Stage N2 and Stage N3 on nights of Day 1/2 and Days 29/30 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant or 10 mg lemborexant, respectively Shows the change (least squares mean) from baseline in fractions in sleep during sleep. During non-rapid eye movement (NREM) sleep on the nights of days 1/2 and 29/30 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant Shows the change from baseline in fractions in sleep (least squares mean). Number of sleepy minutes during non-REM sleep on nights 1/2 and 29/30 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant Changes from baseline (least squares means) are shown. Fractions of REM latency from baseline on nights of Days 1/2 and 29/30 in patients treated with placebo, 6.25 mg zolpidem, 5 mg lemborexant, or 10 mg lemborexant Mean change value is shown.

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

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

を有する化合物を指し、これは、（１Ｒ，２Ｓ）－２－（（（２，４－ジメチルピリミジン－５－イル）オキシ）メチル）－２－（３－フルオロフェニル）－Ｎ－（５－フルオロピリジン－２－イル）シクロプロパンカルボキサミド又は（１Ｒ，２Ｓ）－２－（（（２，４－ジメチルピリミジン－５－イル）オキシ）メチル）－２－（３－フルオロフェニル）－Ｎ－（５－フルオロピリジン－２－イル）シクロプロパン－１－カルボキサミドとしても知られる。 As used herein, the term "lemborexant" has the structure:

(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-( Also known as 5-fluoropyridin-2-yl)cyclopropane-1-carboxamide.

As used herein, the term "therapeutically effective amount" includes, but is not limited to, reduction in subjective sleep onset latency, improvement in subjective sleep efficiency, reduction in subjective sleep onset, or improvement in insomnia. , means an amount sufficient to produce the intended result. The present disclosure involves administering a therapeutically effective amount of lemborexant or a pharmaceutically acceptable salt thereof to a subject. 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.

As used herein, the term "pharmaceutically acceptable salt" is 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, hydrobromic, sulfuric, phosphoric, nitric; 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, naphthalene (b) salts formed from elemental anions such as chlorine, bromine and iodine; 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.

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

In some embodiments, the composition further comprises at least one additional pharmaceutically acceptable component. In some embodiments, the at least one additional pharmaceutically acceptable component is selected from pharmaceutically acceptable carriers, pharmaceutically acceptable vehicles and pharmaceutically acceptable excipients. be.

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

As used herein, the term "pharmaceutically acceptable excipient" refers to a vehicle (e.g., water, capsules, shells, etc.), diluents or inert ingredients used as constituents. The term may include aggregating functions (e.g., binders), disintegrating functions (e.g., disintegrants), lubricating functions (e.g., lubricants) and/or other functions (e.g., solvents, surfactants, etc.). It also includes inert ingredients that are applied to the product.

As used herein, the term "subject" means a mammalian subject, eg, an animal subject such as a human. As used herein, a subject can be of any age. In some embodiments, the subject may be 18 years of age or older. In some embodiments, the subject may be 55 years of age or older.

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

As used herein, the term "subjective sleep onset latency" is abbreviated "sSOL" and means an estimate of the number of minutes from when a subject attempts to fall asleep to sleep onset. In some embodiments, sSOL is derived from data entered in the subject's sleep diary.

As used herein, the term “subjective nocturnal awakening” is abbreviated “sWASO” and is operationalized as the time at which the subject leaves the bed for the day after the initial sleep onset, whether the subject attempts to sleep that night. Means the sum of nocturnal wakefulness minute estimates up to the point of ceasing. In some embodiments, sWASO is derived from data entered in the subject's sleep diary. As used herein, "sWASO improvement" means a decrease in sWASO.

As used herein, the term "subjective total sleep time" is abbreviated "sTST" and is the derived number of sleep minutes from sleep onset to the time the subject stopped trying to sleep that night. means. In some embodiments, the sTST is derived from data entered in the subject's sleep diary.

As used herein, the term "subjective sleep efficiency" is abbreviated "sSE" and is from the time the subject reports that they attempted to sleep that night. The ratio of sTST per subjective time in bed calculated as the interval to the time point (operated as the time the subject left the bed for the day) and sleep state derived by subtracting sWASO from subjective time in bed. It means time. As used herein, "improved sleep efficiency in subjective sleep efficiency (sSE)" means an increase in sleep efficiency in subjective sleep efficiency (sSE).

Subjective determination of the aforementioned sleep parameters are known in the art. In some embodiments, sleep parameters are, for example, subject interviews, sleep diaries, or standardized questionnaires on how restorative and restful sleep was (e.g., Pittsburgh Sleep Quality Index). (Buysse et al., Psychiatry Research (1989), 28(2), 193-213)).

In some embodiments, a sleep diary is used to include subjective sleep onset latency (sSOL), subjective sleep efficiency (sSE), subjective WASO (sWASO) and subjective total sleep time (sTST). Sleep parameters reported by the subjects were assessed (ie, subjective ratings). Subjects are 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 feeling of sleep quality the previous night by asking: "How would you rate the quality of your sleep last night?" mosquito?". Subjects rated their sleep quality on a scale of 1 to 9, with 1 if they slept very little and 9 if they slept very well. In some embodiments, a sleep diary was used to assess subjective scores for morning sleepiness with the following question: "How alert/sleepy are you this morning?" Subjects rated their sleepiness/arousal level on a Likert scale from 1 to 9, with 1 being very sleepy and 9 being very alert.

As used herein, the term "Insomnia Severity Index" is abbreviated as "ISI" and is calculated using a 7-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). (2) sleep maintenance; (3) early morning awakening problems; (4) sleep dissatisfaction; and (7) the distress caused by sleep difficulties. Each item is scored using a 5-point scale (0=no problem to 4=very serious problem), yielding a total score of 0-28. Total ISI scores (items (1)-(7)) and daytime functioning (items (4)-(7)) are analyzed separately.

As used herein, the term "insomnia" means a disorder defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (2013; "DSM-V") with the following diagnostic criteria: :
A. The subject's predominant complaint is dissatisfaction with sleep quantity or quality with one (or more) of the following symptoms:
1. Difficulty falling asleep (in children this can manifest as difficulty falling asleep in the absence of a carer).
2. It is characterized by difficulty maintaining sleep, frequent awakenings or problems re-entering sleep after awakening (in children this can manifest as difficulty re-entering sleep in the absence of a carer).
3. Waking up early in the morning when you can't go back to sleep.
B. Sleep disorders cause clinically significant distress or impairment in social, occupational, educational, academic, behavioral or other important areas of functioning.
C. Difficulty sleeping occurs at least 3 nights a week.
D. Difficulty sleeping has persisted for at least 3 months.
E. Difficulty sleeping occurs despite adequate sleep opportunities.
F. Insomnia is poorly explained by, and does not occur exclusively in the course of, other sleep-wake disorders (eg, narcolepsy, respiratory-related sleep disorders, circadian rhythm sleep-wake disorders, parasomnias).
G. Insomnia is not due to the physiological effects of substances (eg, drugs of abuse, medications).
H. The coexistence of psychiatric disorders and medical conditions does not fully explain the predominant complaint of insomnia.

The term "insomnia" also means sleep disorders characterized by symptoms including, but not limited to, difficulty falling asleep, difficulty falling asleep, intermittent awakening and/or waking up too early. The term also includes 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.

As used herein, the term “sustained sleep latency” is abbreviated “LPS” and means the number of minutes from lights out to the first of 20 consecutive epochs (10 minutes) of non-awake state.

In some embodiments, sleep parameters are objectively determined using overnight polysomnography. Overnight polysomnography is the monitoring of multiple electrophysiological parameters during sleep, generally including measurement of EEG, electrooculographic and electromyographic activity, as well as other measurements. Using these results in conjunction with observations, the following can be objectively measured: continuous sleep latency (LPS), wake after sleep (WASO), wake after sleep during the second half of the night (WASO2H), sleep efficiency (SE). and total sleep time (TST).

As used herein, the term "about" means ±10% of the stated value. For example, for an embodiment directed to a method in which subjective sleep latency is reduced by about 10 minutes, then subjective sleep latency is reduced by an amount of time in the range of 9 minutes to 11 minutes.

As used herein, the term "immediately before going to bed" means within 5 minutes of starting to get ready for bed or going to bed. In some embodiments, the patient takes lemborexant or a pharmaceutically acceptable salt thereof within 5 minutes of starting to go to bed. In some embodiments, the patient takes lemborexant or a pharmaceutically acceptable salt thereof within 2 minutes of starting to go to bed. In some embodiments, the patient takes lemborexant or a pharmaceutically acceptable salt thereof within 5 minutes of going to bed. In some embodiments, the patient takes lemborexant or a pharmaceutically acceptable salt thereof within 2 minutes of going to bed. In some embodiments, the patient takes lemborexant or a pharmaceutically acceptable salt thereof immediately after going to bed.

Method of Reducing Subjective Sleep Latency (sSOL) Provided herein is a method of reducing subjective sleep latency (sSOL) in a subject, comprising administering to the subject 5 mg or 10 mg lemborexant or an equivalent dose thereof. A method is provided comprising administering a pharmaceutically acceptable salt. As used herein, lemborexant or lemborexant for use in reducing sSOL in a subject comprising administering 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof to the subject. Pharmaceutically acceptable salts are also disclosed.

In some embodiments, sSOL decreases for at least one week. In some embodiments, sSOL decreases for at least one month. In some embodiments, sSOL decreases for at least 2 months. In some embodiments, sSOL decreases for at least 3 months. In some embodiments, sSOL decreases for at least 6 months. In some embodiments, sSOL decreases for at least 9 months. In some embodiments, sSOL decreases for at least 12 months. In some embodiments, sSOL decreases for at least 18 months. In some embodiments, sSOL decreases over 2 years.

In some embodiments, sSOL decreases relative to baseline for at least one week. In some embodiments, sSOL decreases over baseline for at least one month. In some embodiments, sSOL decreases over baseline for at least 2 months. In some embodiments, sSOL decreases over baseline for at least 3 months. In some embodiments, sSOL decreases over baseline for at least 6 months. In some embodiments, sSOL decreases over baseline for at least 9 months. In some embodiments, sSOL decreases over baseline for at least 12 months. In some embodiments, sSOL decreases over baseline for at least 18 months. In some embodiments, sSOL decreases over baseline for 2 years or more.

In some embodiments, lemborexant or a salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for two years or longer.

In some embodiments, sSOL is 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 relative to baseline , at least 150 minutes or at least 180 minutes. In some embodiments, sSOL is 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 relative to baseline , 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.

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.

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.

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 over baseline. In some embodiments, sSOL is decreased by at least 23 minutes over 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 over 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.

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.

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.

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 over baseline. In some embodiments, sSOL is decreased by about 15 minutes relative to baseline. In some embodiments, sSOL is decreased by about 16 minutes over baseline. In some embodiments, sSOL is decreased by about 17 minutes relative to baseline. In some embodiments, sSOL is decreased by about 18 minutes over baseline. In some embodiments, sSOL is decreased by about 19 minutes over baseline. In some embodiments, sSOL is decreased by about 20 minutes relative to baseline.

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

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 over 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.

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

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

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

In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the 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 the 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 the subject and sSOL is reduced by about 32 minutes.

In some embodiments, 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 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.

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.

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.

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, 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.

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.

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, sSOL is 45 minutes or less.

In some embodiments, the sSOL is 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 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.

In some embodiments, sSOL is about 1 minute or less. In some embodiments, sSOL is about 2 minutes or less. In some embodiments, sSOL is about 3 minutes or less. In some embodiments, sSOL is about 4 minutes or less. In some embodiments, sSOL is about 5 minutes or less. In some embodiments, the sSOL is about 6 minutes or less. In some embodiments, 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, sSOL is about 10 minutes or less.

In some embodiments, the sSOL is about 11 minutes or less. In some embodiments, 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, sSOL is about 15 minutes or less. In some embodiments, 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.

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

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

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

In some embodiments, the subject has insomnia.

Method of Reducing Subjective Suspension (sWASO) Provided herein is a method of reducing Subjective Suspension (sWASO) in a subject, comprising: Methods are provided that include administering an acceptable salt. As used herein, lemborexant or lemborexant for use in reducing sWASO in a subject comprising administering 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof to the subject. Pharmaceutically acceptable salts are also disclosed.

In some embodiments, sWASO decreases over at least one month. In some embodiments, sWASO decreases for at least 2 months. In some embodiments, sWASO decreases for at least 3 months. In some embodiments, sWASO decreases for at least 6 months. In some embodiments, sWASO decreases for at least 9 months. In some embodiments, sWASO decreases over at least 12 months. In some embodiments, sWASO decreases for at least 18 months. In some embodiments, sWASO decreases over 2 years.

In some embodiments, sWASO decreases over baseline for at least one month. In some embodiments, sWASO decreases over baseline for at least 2 months. In some embodiments, sWASO decreases over baseline for at least 3 months. In some embodiments, sWASO decreases over baseline for at least 6 months. In some embodiments, sWASO decreases over baseline for at least 9 months. In some embodiments, sWASO decreases over baseline for at least 12 months. In some embodiments, sWASO decreases over baseline for at least 18 months. In some embodiments, sWASO decreases over baseline over 2 years.

In some embodiments, lemborexant or a salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for two years or more.

In some embodiments, sWASO is 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 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 relative to baseline , 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, 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 less.

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.

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

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

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

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

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

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.

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.

In some embodiments, sWASO is decreased by about 21 minutes relative to baseline. In some embodiments, sWASO is decreased by about 22 minutes over 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 over 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.

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.

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 over 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.

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.

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

In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the sWASO decreases by at least 20 minutes relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the sWASO decreases by at least 23 minutes over baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the sWASO decreases by at least 42 minutes over baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the sWASO decreases by at least 51 minutes over baseline.

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

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

In some embodiments, sWASO is 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, Reduce by at least 150 minutes or at least 180 minutes. In some embodiments, sWASO is 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 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.

In some embodiments, sWASO is decreased by at least 1 minute relative to placebo. In some embodiments, sWASO is decreased by at least 2 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 3 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 4 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 5 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 6 minutes relative to placebo. In some embodiments, sWASO is decreased 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 decreased by at least 9 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 10 minutes relative to placebo.

In some embodiments, sWASO is decreased by at least 11 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 12 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 13 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 14 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 15 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 16 minutes relative to placebo. In some embodiments, sWASO is decreased 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 decreased by at least 19 minutes relative to placebo. In some embodiments, sWASO is reduced by at least 20 minutes relative to placebo.

In some embodiments, sWASO is decreased by at least 21 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 22 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 23 minutes relative to placebo. In some embodiments, sWASO is decreased 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 decreased by at least 26 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 27 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 28 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 29 minutes relative to placebo. In some embodiments, sWASO is decreased by at least 30 minutes relative to placebo.

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 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 reduced by about 10 minutes relative to placebo.

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 decreased 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.

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.

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

In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the sWASO is reduced by at least 5 minutes relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the sWASO is reduced by at least 13 minutes relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the sWASO is reduced by at least 14 minutes relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the sWASO 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 the subject and the 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 the subject and the 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 the subject and the sWASO is reduced by about 15 minutes relative to placebo.

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

In some embodiments, the subject has insomnia.

Method of Improving Subjective Sleep Efficiency (sSE) Provided herein is a method of improving subjective sleep efficiency (sSE) in a subject, comprising: Methods are provided that include administering an acceptable salt. As used herein, lemborexant or lemborexant for use in improving sSE in a subject comprising administering 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof to the subject. Pharmaceutically acceptable salts are also disclosed.

In some embodiments, the sSE is improved for at least 1 month. In some embodiments, the sSE is improved for at least 2 months. In some embodiments, the sSE is improved for at least 3 months. In some embodiments, the 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 over 2 years or more.

In some embodiments, the sSE improves over baseline for at least one month. In some embodiments, the sSE is improved over baseline for at least 2 months. In some embodiments, the sSE is improved over baseline for at least 3 months. In some embodiments, sSE is improved over baseline for at least 6 months. In some embodiments, the sSE is improved over baseline for at least 9 months. In some embodiments, sSE is improved over baseline for at least 12 months. In some embodiments, sSE is improved over baseline for at least 18 months. In some embodiments, sSE improves over baseline over two years.

In some embodiments, lemborexant or a salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for two years or longer.

In some embodiments, sSE is 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% of baseline be improved. In some embodiments, sSE is 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% relative to baseline , 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% improvement.

In some embodiments, sSE is improved by at least 1% over baseline. In some embodiments, sSE is improved by at least 2% over baseline. In some embodiments, sSE is improved by at least 3% over baseline. In some embodiments, sSE is improved by at least 4% over baseline. In some embodiments, sSE is improved by at least 5% over baseline. In some embodiments, sSE is improved by at least 6% over baseline. In some embodiments, sSE is improved by at least 7% over baseline. In some embodiments, sSE is improved by at least 8% over baseline. In some embodiments, sSE is improved by at least 9% over baseline.

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

In some embodiments, sSE is improved by at least 20% over baseline. In some embodiments, sSE is improved by at least 21% over baseline. In some embodiments, sSE is improved by at least 22% over baseline. In some embodiments, sSE is improved by at least 23% over baseline. In some embodiments, sSE is improved by at least 24% over baseline. In some embodiments, sSE is improved by at least 25% over baseline.

In some embodiments, sSE is improved by about 1% over baseline. In some embodiments, sSE is improved by about 2% over baseline. In some embodiments, sSE is improved by about 3% over baseline. In some embodiments, sSE is improved by about 4% over baseline. In some embodiments, sSE is improved by about 5% over baseline. In some embodiments, sSE is improved by about 6% over baseline. In some embodiments, sSE is improved by about 7% over baseline. In some embodiments, sSE is improved by about 8% over baseline. In some embodiments, sSE is improved by about 9% over baseline.

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

In some embodiments, sSE is improved by about 20% over baseline. In some embodiments, sSE is improved by about 21% over baseline. In some embodiments, sSE is improved by about 22% over baseline. In some embodiments, sSE is improved by about 23% over baseline. In some embodiments, sSE is improved by about 24% over baseline. In some embodiments, sSE is improved by about 25% over baseline.

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

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

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

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

In some embodiments, sSE is 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% improvement over placebo be done. In some embodiments, the sSE is 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% improvement.

In some embodiments, sSE is improved by at least 1% over placebo. In some embodiments, sSE is improved by at least 2% over placebo. In some embodiments, sSE is improved by at least 3% over placebo. In some embodiments, sSE is improved by at least 4% over placebo. In some embodiments, sSE is improved by at least 5% over placebo.

In some embodiments, sSE is improved by at least 6% over placebo. In some embodiments, sSE is improved by at least 7% over placebo. In some embodiments, sSE is improved by at least 8% over placebo. In some embodiments, sSE is improved by at least 9% over placebo. In some embodiments, sSE is improved by at least 10% over placebo.

In some embodiments, sSE is improved by about 1% over placebo. In some embodiments, sSE is improved by about 2% over placebo. In some embodiments, sSE is improved by about 3% over placebo. In some embodiments, sSE is improved by about 4% over placebo. In some embodiments, sSE is improved by about 5% over placebo.

In some embodiments, sSE is improved by about 6% over placebo. In some embodiments, sSE is improved by about 7% over placebo. In some embodiments, sSE is improved by about 8% over placebo. In some embodiments, sSE is improved by about 9% over placebo. In some embodiments, sSE is improved by about 10% over placebo.

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

In some embodiments, the subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the sSE improves by at least 2% over baseline. In some embodiments, the subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, and the sSE improves by at least 4% over baseline.

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

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

Method of Reducing Long-Term Sleep Latency (LPS) Provided herein is a method of reducing long-term sleep latency (LPS) in a subject, comprising administering to the subject 5 mg or 10 mg lemborexant or a pharmaceutically equivalent dose thereof. Methods are provided that include administering an acceptable salt. As used herein, lemborexant or lemborexant for use in reducing LPS in a subject comprising administering 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof to the subject. Pharmaceutically acceptable salts are also disclosed.

In some embodiments, LPS is administered 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 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, LPS decreases for at least 1 day. In some embodiments, LPS decreases for at least 2 days. In some embodiments, LPS decreases for at least 3 days. In some embodiments, LPS decreases for at least 4 days. In some embodiments, LPS decreases for at least 5 days. In some embodiments, LPS decreases for at least 6 days. In some embodiments, LPS decreases for at least 7 days. In some embodiments, LPS decreases for at least 8 days. In some embodiments, LPS decreases for at least 9 days. In some embodiments, LPS decreases for at least 10 days.

In some embodiments, LPS decreases for at least 11 days. In some embodiments, LPS decreases for at least 12 days. In some embodiments, LPS decreases for at least 13 days. In some embodiments, LPS decreases for at least 14 days. In some embodiments, LPS decreases for at least 15 days. In some embodiments, LPS decreases for at least 16 days. In some embodiments, LPS decreases for at least 17 days. In some embodiments, LPS decreases for at least 18 days. In some embodiments, LPS decreases for at least 19 days.

In some embodiments, LPS decreases for at least 20 days. In some embodiments, LPS decreases for at least 21 days. In some embodiments, LPS decreases for at least 22 days. In some embodiments, LPS decreases for at least 23 days. In some embodiments, LPS decreases for at least 24 days. In some embodiments, LPS decreases for at least 25 days. In some embodiments, LPS decreases for at least 26 days. In some embodiments, LPS decreases for at least 27 days. In some embodiments, LPS decreases for at least 28 days. In some embodiments, LPS decreases for at least 29 days. In some embodiments, LPS decreases for at least 30 days.

In some embodiments, LPS decreases for at least one month. In some embodiments, LPS decreases for at least 2 months. In some embodiments, LPS decreases for at least 3 months. In some embodiments, LPS decreases for at least 6 months. In some embodiments, LPS decreases for at least 9 months. In some embodiments, LPS decreases for at least 12 months. In some embodiments, LPS decreases for at least 18 months. In some embodiments, LPS decreases over 2 years.

In some embodiments, LPS decreases for at least one month. In some embodiments, LPS decreases over baseline for at least 2 months. In some embodiments, LPS decreases over baseline for at least 3 months. In some embodiments, LPS decreases over baseline for at least 6 months. In some embodiments, LPS decreases over baseline for at least 9 months. In some embodiments, LPS decreases over baseline for at least 12 months. In some embodiments, LPS decreases over baseline for at least 18 months. In some embodiments, LPS decreases over baseline for 2 years or more.

In some embodiments, lemborexant or a salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for two years or longer.

In some embodiments, LPS is 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 relative to baseline , at least 150 minutes or at least 180 minutes. In some embodiments, LPS is 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 relative to baseline , 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.

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

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.

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.

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.

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

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

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.

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

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

In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and LPS is reduced for at least 16 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the 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 the 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 the subject and the LPS is reduced by about 21 minutes.

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

In some embodiments, 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 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.

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.

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.

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.

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.

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.

In some embodiments, the LPS is 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 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.

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.

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.

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.

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.

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.

In some embodiments, the subject has insomnia.

Method of reducing wake after wakefulness (WASO) Provided herein is a method of reducing wake after awakening (WASO) in a subject comprising: 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof A method is provided comprising administering a As used herein, lemborexant or lemborexant for use in reducing WASO in a subject comprising administering 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof to the subject. Pharmaceutically acceptable salts are also disclosed.

In some embodiments, WASO is administered 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 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, WASO decreases for at least 1 day. In some embodiments, WASO decreases over at least 2 days. In some embodiments, WASO decreases over at least 3 days. In some embodiments, WASO decreases for at least 4 days. In some embodiments, WASO decreases for at least 5 days. In some embodiments, WASO decreases for at least 6 days. In some embodiments, WASO decreases for at least 7 days. In some embodiments, WASO decreases for at least 8 days. In some embodiments, WASO decreases for at least 9 days. In some embodiments, WASO decreases for at least 10 days.

In some embodiments, WASO decreases for at least 11 days. In some embodiments, WASO decreases for at least 12 days. In some embodiments, WASO decreases for at least 13 days. In some embodiments, WASO decreases for at least 14 days. In some embodiments, WASO decreases for at least 15 days. In some embodiments, WASO decreases for at least 16 days. In some embodiments, WASO decreases for at least 17 days. In some embodiments, WASO decreases for at least 18 days. In some embodiments, WASO decreases for at least 19 days.

In some embodiments, WASO decreases for at least 20 days. In some embodiments, WASO decreases for at least 21 days. In some embodiments, WASO decreases for at least 22 days. In some embodiments, WASO decreases for at least 23 days. In some embodiments, WASO decreases for at least 24 days. In some embodiments, WASO decreases for at least 25 days. In some embodiments, WASO decreases for at least 26 days. In some embodiments, WASO decreases for at least 27 days. In some embodiments, WASO decreases for at least 28 days. In some embodiments, WASO decreases for at least 29 days. In some embodiments, WASO decreases for at least 30 days.

In some embodiments, WASO is 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, relative to baseline 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, Decrease for 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, WASO decreases over baseline for at least 1 day. In some embodiments, WASO decreases over baseline for at least 2 days. In some embodiments, WASO decreases over baseline for at least 3 days. In some embodiments, WASO decreases over baseline for at least 4 days. In some embodiments, WASO decreases over baseline for at least 5 days. In some embodiments, WASO decreases over baseline for at least 6 days. In some embodiments, WASO decreases over baseline for at least 7 days. In some embodiments, WASO decreases over baseline for at least 8 days. In some embodiments, WASO decreases over baseline for at least 9 days. In some embodiments, WASO decreases over baseline for at least 10 days.

In some embodiments, WASO decreases over baseline for at least 11 days. In some embodiments, WASO decreases over baseline for at least 12 days. In some embodiments, WASO decreases over baseline for at least 13 days. In some embodiments, WASO decreases over baseline for at least 14 days. In some embodiments, WASO decreases over baseline for at least 15 days. In some embodiments, WASO decreases over baseline for at least 16 days. In some embodiments, WASO decreases over baseline for at least 17 days. In some embodiments, WASO decreases over baseline for at least 18 days. In some embodiments, WASO decreases over baseline for at least 19 days.

In some embodiments, WASO decreases over baseline for at least 20 days. In some embodiments, WASO decreases over baseline for at least 21 days. In some embodiments, WASO decreases over baseline for at least 22 days. In some embodiments, WASO decreases over baseline for at least 23 days. In some embodiments, WASO decreases over baseline for at least 24 days. In some embodiments, WASO decreases over baseline for at least 25 days. In some embodiments, WASO decreases over baseline for at least 26 days. In some embodiments, WASO decreases over baseline for at least 27 days. In some embodiments, WASO decreases relative to baseline for at least 28 days. In some embodiments, WASO decreases over baseline for at least 29 days. In some embodiments, WASO decreases over baseline for at least 30 days.

In some embodiments, WASO decreases for at least one month. In some embodiments, WASO decreases for at least 2 months. In some embodiments, WASO decreases for at least 3 months. In some embodiments, WASO decreases for at least 6 months. In some embodiments, WASO decreases for at least 9 months. In some embodiments, WASO decreases for at least 12 months. In some embodiments, WASO decreases for at least 18 months. In some embodiments, WASO decreases over 2 years.

In some embodiments, WASO decreases over baseline for at least one month. In some embodiments, WASO decreases over baseline for at least 2 months. In some embodiments, WASO decreases over baseline for at least 3 months. In some embodiments, WASO decreases over baseline for at least 6 months. In some embodiments, WASO decreases over baseline for at least 9 months. In some embodiments, WASO decreases over baseline for at least 12 months. In some embodiments, WASO decreases over baseline for at least 18 months. In some embodiments, WASO decreases over baseline over 2 years.

In some embodiments, lemborexant or a salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for two years or more.

In some embodiments, WASO is 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 relative to baseline , at least 150 minutes or at least 180 minutes. In some embodiments, WASO is 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, 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.

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

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

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

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

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

In some embodiments, WASO is decreased by at least 52 minutes relative to baseline. In some embodiments, WASO is decreased by at least 53 minutes relative to baseline. In some embodiments, WASO is decreased by at least 54 minutes relative to baseline. In some embodiments, WASO is decreased by at least 55 minutes relative to baseline. In some embodiments, WASO is decreased by at least 56 minutes relative to baseline. In some embodiments, WASO is decreased by at least 57 minutes relative to baseline. In some embodiments, WASO is decreased by at least 58 minutes relative to baseline. In some embodiments, WASO is decreased by at least 59 minutes relative to baseline. In some embodiments, WASO is decreased by at least 60 minutes relative to baseline.

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

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

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

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

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

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

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

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

In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the WASO decreases by about 44 minutes relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the WASO decreases by about 50 minutes relative to baseline.

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

In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the WASO decreases by about 46 minutes relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and the WASO decreases by about 60 minutes relative to baseline.

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

In some embodiments, WASO is 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, Reduce by at least 150 minutes or at least 180 minutes. In some embodiments, WASO is 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 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 Decrease for at least 35 minutes.

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

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

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

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

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 decreased by about 8 minutes relative to baseline. In some embodiments, WASO is decreased by about 9 minutes relative to baseline. In some embodiments, WASO is reduced by about 10 minutes relative to placebo.

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

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

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

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

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

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

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

In some embodiments, WASO is administered to Zolpidem for 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, Reduce by at least 150 minutes or at least 180 minutes. In some embodiments, WASO is administered to Zolpidem for 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 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes.

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

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

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

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

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

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

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

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

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

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

In some embodiments, the subject has insomnia.

Methods of reducing wake up after awakening during the late night (WASO2H) Provided herein is a method of reducing wake up after awakening during the late night (WASO2H) in a subject, comprising administering 5 mg or 10 mg lemborexant or an equivalent dose to the subject A method is provided comprising administering a pharmaceutically acceptable salt thereof. As used herein, lemborexant or lemborexant for use in reducing WASO2H in a subject comprising administering 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof to the subject. Pharmaceutically acceptable salts are also disclosed.

In some embodiments, WASO2H is administered 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 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 decreases for at least 1 day. In some embodiments, WASO2H decreases for at least 2 days. In some embodiments, WASO2H decreases for at least 3 days. In some embodiments, WASO2H decreases for at least 4 days. In some embodiments, WASO2H decreases for at least 5 days. In some embodiments, WASO2H decreases for at least 6 days. In some embodiments, WASO2H decreases for at least 7 days. In some embodiments, WASO2H decreases for at least 8 days. In some embodiments, WASO2H decreases for at least 9 days. In some embodiments, WASO2H decreases for at least 10 days.

In some embodiments, WASO2H decreases for at least 11 days. In some embodiments, WASO2H decreases for at least 12 days. In some embodiments, WASO2H decreases for at least 13 days. In some embodiments, WASO2H decreases for at least 14 days. In some embodiments, WASO2H decreases for at least 15 days. In some embodiments, WASO2H decreases for at least 16 days. In some embodiments, WASO2H decreases for at least 17 days. In some embodiments, WASO2H decreases for at least 18 days. In some embodiments, WASO2H decreases for at least 19 days.

In some embodiments, WASO2H decreases for at least 20 days. In some embodiments, WASO2H decreases for at least 21 days. In some embodiments, WASO2H decreases for at least 22 days. In some embodiments, WASO2H decreases for at least 23 days. In some embodiments, WASO2H decreases for at least 24 days. In some embodiments, WASO2H decreases for at least 25 days. In some embodiments, WASO2H decreases for at least 26 days. In some embodiments, WASO2H decreases for at least 27 days. In some embodiments, WASO2H decreases for at least 28 days. In some embodiments, WASO2H decreases for at least 29 days. In some embodiments, WASO2H decreases for at least 30 days.

In some embodiments, WASO2H is 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, relative to baseline 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, Decrease for 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 decreases relative to baseline for at least 1 day. In some embodiments, WASO2H decreases relative to baseline for at least 2 days. In some embodiments, WASO2H decreases relative to baseline for at least 3 days. In some embodiments, WASO2H decreases relative to baseline for at least 4 days. In some embodiments, WASO2H decreases relative to baseline for at least 5 days. In some embodiments, WASO2H decreases relative to baseline for at least 6 days. In some embodiments, WASO2H decreases relative to baseline for at least 7 days. In some embodiments, WASO2H decreases relative to baseline for at least 8 days. In some embodiments, WASO2H decreases over baseline for at least 9 days. In some embodiments, WASO2H decreases over baseline for at least 10 days.

In some embodiments, WASO2H decreases over baseline for at least 11 days. In some embodiments, WASO2H decreases relative to baseline for at least 12 days. In some embodiments, WASO2H decreases relative to baseline for at least 13 days. In some embodiments, WASO2H decreases relative to baseline for at least 14 days. In some embodiments, WASO2H decreases relative to baseline for at least 15 days. In some embodiments, WASO2H decreases relative to baseline for at least 16 days. In some embodiments, WASO2H decreases relative to baseline for at least 17 days. In some embodiments, WASO2H decreases relative to baseline for at least 18 days. In some embodiments, WASO2H decreases relative to baseline for at least 19 days.

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

In some embodiments, WASO2H decreases for at least 1 month. In some embodiments, WASO2H decreases for at least 2 months. In some embodiments, WASO2H decreases for at least 3 months. In some embodiments, WASO2H decreases for at least 6 months. In some embodiments, WASO2H decreases for at least 9 months. In some embodiments, WASO2H decreases for at least 12 months. In some embodiments, WASO2H decreases for at least 18 months. In some embodiments, WASO2H declines over 2 years.

In some embodiments, WASO2H decreases over baseline for at least one month. In some embodiments, WASO2H decreases over baseline for at least 2 months. In some embodiments, WASO2H decreases over baseline for at least 3 months. In some embodiments, WASO2H decreases over baseline for at least 6 months. In some embodiments, WASO2H decreases over baseline for at least 9 months. In some embodiments, WASO2H decreases over baseline for at least 12 months. In some embodiments, WASO2H decreases over baseline for at least 18 months. In some embodiments, WASO2H decreases over baseline for 2 years or more.

In some embodiments, lemborexant or a salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for two years or longer.

In some embodiments, WASO2H is 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 relative to baseline , at least 150 minutes or at least 180 minutes. In some embodiments, WASO2H is 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 relative to baseline , 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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and WASO2H decreases by about 27 minutes relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject, and WASO2H decreases by about 30 minutes relative to baseline.

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

In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and WASO2H decreases by about 28 minutes relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to the subject and WASO2H decreases by about 37 minutes relative to baseline.

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

In some embodiments, WASO2H is 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, Reduce by at least 150 minutes or at least 180 minutes. In some embodiments, WASO2H is 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 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 Decrease for at least 35 minutes.

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.

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.

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.

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.

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.

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 decreases by about 20 minutes relative to placebo.

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 decreases by about 30 minutes relative to placebo.

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 decreases by about 35 minutes relative to placebo.

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

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

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

In some embodiments, WASO2H is administered to Zolpidem for 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, Reduce by at least 150 minutes or at least 180 minutes. In some embodiments, WASO2H is administered to Zolpidem for 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 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes.

In some embodiments, WASO2H is decreased relative to zolpidem by at least 1 minute. In some embodiments, WASO2H is decreased by at least 2 min 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 min relative to zolpidem. In some embodiments, WASO2H is reduced relative to zolpidem by at least 5 minutes. In some embodiments, WASO2H is decreased by at least 6 minutes relative to zolpidem. In some embodiments, WASO2H is reduced relative to zolpidem by at least 7 minutes. In some embodiments, WASO2H is decreased by at least 8 minutes relative to zolpidem. In some embodiments, WASO2H is decreased by at least 9 min relative to zolpidem. In some embodiments, WASO2H is reduced relative to zolpidem by at least 10 minutes.

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

In some embodiments, WASO2H decreases relative to zolpidem by at least 21 minutes. In some embodiments, WASO2H decreases relative to zolpidem by at least 22 minutes. In some embodiments, WASO2H decreases relative to zolpidem by at least 23 minutes. In some embodiments, WASO2H decreases relative to zolpidem by at least 24 minutes. In some embodiments, WASO2H decreases relative to zolpidem by at least 25 minutes.

In some embodiments, WASO2H is decreased relative to zolpidem by about 1 minute. In some embodiments, WASO2H is decreased by about 2 minutes relative to Zolpidem. In some embodiments, WASO2H is reduced by about 3 minutes relative to zolpidem. In some embodiments, WASO2H is reduced by about 4 minutes relative to zolpidem. In some embodiments, WASO2H is decreased relative to zolpidem by about 5 minutes. In some embodiments, WASO2H is reduced by about 6 minutes relative to zolpidem. In some embodiments, WASO2H is reduced relative to zolpidem by about 7 minutes. 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 relative to zolpidem by about 10 minutes.

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

In some embodiments, WASO2H decreases relative to zolpidem by about 21 minutes. In some embodiments, WASO2H is reduced relative to zolpidem by about 22 minutes. In some embodiments, WASO2H is reduced relative to zolpidem by about 23 minutes. In some embodiments, WASO2H decreases relative to zolpidem by about 24 minutes. In some embodiments, WASO2H decreases relative to zolpidem by about 25 minutes.

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

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

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

In some embodiments, the subject has insomnia.

Method of Improving Sleep Efficiency (SE) Provided herein is a method of improving sleep efficiency (SE) in a subject, comprising administering to the subject 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof. A method is provided comprising administering a

In some embodiments, the SE is 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 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 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.

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.

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.

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 improves for at least 3 months. In some embodiments, SE improves for at least 6 months. In some embodiments, SE improves for at least 9 months. In some embodiments, SE improves for at least 12 months. In some embodiments, SE improves for at least 18 months. In some embodiments, SE is improved over 2 years.

In some embodiments, SE is improved for at least 1 month. In some embodiments, SE improves over baseline for at least 2 months. In some embodiments, SE improves over baseline for at least 3 months. In some embodiments, SE improves over baseline for at least 6 months. In some embodiments, SE improves over baseline for at least 9 months. In some embodiments, SE improves over baseline for at least 12 months. In some embodiments, SE improves over baseline for at least 18 months. In some embodiments, SE improves over baseline over 2 years.

In some embodiments, lemborexant or a salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 3 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 9 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or a salt thereof is administered to the subject for two years or longer.

In some embodiments, SE is 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% of baseline be improved. In some embodiments, SE is 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% of baseline , 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% improvement.

In some embodiments, SE is improved by at least 1% over baseline. In some embodiments, SE is improved by at least 2% over baseline. In some embodiments, SE is improved by at least 3% over baseline. In some embodiments, SE is improved by at least 4% over baseline. In some embodiments, SE is improved by at least 5% over baseline. In some embodiments, SE is improved by at least 6% over baseline. In some embodiments, SE is improved by at least 7% over baseline. In some embodiments, SE is improved by at least 8% over baseline. In some embodiments, SE is improved by at least 9% over baseline.

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

In some embodiments, SE is improved by at least 20% over baseline. In some embodiments, SE is improved by at least 21% over baseline. In some embodiments, SE is improved by at least 22% over baseline. In some embodiments, SE is improved by at least 23% over baseline. In some embodiments, SE is improved by at least 24% over baseline. In some embodiments, SE is improved by at least 25% over baseline.

In some embodiments, SE is improved by about 1% over baseline. In some embodiments, SE is improved by about 2% over baseline. In some embodiments, SE is improved by about 3% over baseline. In some embodiments, SE is improved by about 4% over baseline. In some embodiments, SE is improved by about 5% over baseline. In some embodiments, SE is improved by about 6% over baseline. In some embodiments, SE is improved by about 7% over baseline. In some embodiments, SE is improved by about 8% over baseline. In some embodiments, SE is improved by about 9% over baseline.

In some embodiments, SE is improved by about 10% over baseline. In some embodiments, SE is improved by about 11% over baseline. In some embodiments, SE is improved by about 12% over baseline. In some embodiments, SE is improved by about 13% over baseline. In some embodiments, SE is improved by about 14% over baseline. In some embodiments, SE is improved by about 15% over baseline. In some embodiments, SE is improved by about 16% over baseline. In some embodiments, SE is improved by about 17% over baseline. In some embodiments, SE is improved by about 18% over baseline. In some embodiments, SE is improved by about 19% over baseline.

In some embodiments, SE is improved by about 20% over baseline. In some embodiments, SE is improved by about 21% over baseline. In some embodiments, SE is improved by about 22% over baseline. In some embodiments, SE is improved by about 23% over baseline. In some embodiments, SE is improved by about 24% over baseline. In some embodiments, SE is improved by about 25% over baseline.

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

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

In some embodiments, the subject is administered 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by at least 14% over baseline. In some embodiments, the subject is administered 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by at least 15% over baseline.

In some embodiments, the subject is administered 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by about 14% over baseline. In some embodiments, the subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by about 15% over baseline.

In some embodiments, the SE is 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% improvement over placebo be done. In some embodiments, the SE is 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% improvement.

In some embodiments, SE is improved by at least 1% over placebo. In some embodiments, SE is improved by at least 2% over placebo. In some embodiments, SE is improved by at least 3% over placebo. In some embodiments, SE is improved by at least 4% over placebo. In some embodiments, SE is improved by at least 5% over placebo.

In some embodiments, SE is improved by at least 6% over placebo. In some embodiments, SE is improved by at least 7% over placebo. In some embodiments, SE is improved by at least 8% over placebo. In some embodiments, SE is improved by at least 9% over placebo. In some embodiments, SE is improved by at least 10% over placebo.

In some embodiments, SE is improved by at least 11% over placebo. In some embodiments, SE is improved by at least 12% over placebo. In some embodiments, SE is improved by at least 13% over placebo. In some embodiments, SE is improved by at least 14% over placebo. In some embodiments, SE is improved by at least 15% over placebo.

In some embodiments, SE is improved by at least 16% over placebo. In some embodiments, SE is improved by at least 17% over placebo. In some embodiments, SE is improved by at least 18% over placebo. In some embodiments, SE is improved by at least 19% over placebo. In some embodiments, SE is improved by at least 20% over placebo.

In some embodiments, SE is improved by at least 21% over placebo. In some embodiments, SE is improved by at least 22% over placebo. In some embodiments, SE is improved by at least 23% over placebo. In some embodiments, SE is improved by at least 24% over placebo. In some embodiments, SE is improved by at least 25% over placebo.

In some embodiments, SE is improved by about 1% over placebo. In some embodiments, SE is improved by about 2% over placebo. In some embodiments, SE is improved by about 3% over placebo. In some embodiments, SE is improved by about 4% over placebo. In some embodiments, SE is improved by about 5% over placebo.

In some embodiments, SE is improved by about 6% over placebo. In some embodiments, SE is improved by about 7% over placebo. In some embodiments, SE is improved by about 8% over placebo. In some embodiments, SE is improved by about 9% over placebo. In some embodiments, SE is improved by about 10% over placebo.

In some embodiments, SE is improved by about 11% over placebo. In some embodiments, SE is improved by about 12% over placebo. In some embodiments, SE is improved by about 13% over placebo. In some embodiments, SE is improved by about 14% over placebo. In some embodiments, SE is improved by about 15% over placebo.

In some embodiments, SE is improved by about 16% over placebo. In some embodiments, SE is improved by about 17% over placebo. In some embodiments, SE is improved by about 18% over placebo. In some embodiments, SE is improved by about 19% over placebo. In some embodiments, SE is improved by about 20% over placebo.

In some embodiments, SE is improved by about 21% over placebo. In some embodiments, SE is improved by about 22% over placebo. In some embodiments, SE is improved by about 23% over placebo. In some embodiments, SE is improved by about 24% over placebo. In some embodiments, SE is improved by about 25% over placebo.

In some embodiments, the subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by at least 7% over placebo. In some embodiments, the subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by at least 9% over placebo.

In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by about 7% over placebo. In some embodiments, a subject is administered 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by about 9% over placebo.

In some embodiments, the subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by at least 8% over placebo. In some embodiments, the subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by at least 8% over placebo.

In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by about 8% over placebo. In some embodiments, a subject is administered 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof and the SE improves by about 11% over placebo.

In some embodiments, SE is 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% improved over zolpidem be done. In some embodiments, the SE is 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%, improved by at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, or at least 15%.

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

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

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

In some embodiments, SE is improved by about 1% over zolpidem. In some embodiments, SE is improved by about 2% over zolpidem. In some embodiments, SE is improved by about 3% over zolpidem. In some embodiments, SE is improved by about 4% over zolpidem. In some embodiments, SE is improved by about 5% over zolpidem.

In some embodiments, SE is improved by about 6% over zolpidem. In some embodiments, SE is improved by about 7% over zolpidem. In some embodiments, SE is improved by about 8% over zolpidem. In some embodiments, SE is improved by about 9% over zolpidem. In some embodiments, SE is improved by about 10% over zolpidem.

In some embodiments, SE is improved by about 11% over zolpidem. In some embodiments, SE is improved by about 12% over zolpidem. In some embodiments, SE is improved by about 13% over zolpidem. In some embodiments, SE is improved by about 14% over zolpidem. In some embodiments, SE is improved by about 15% relative to zolpidem.

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

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

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

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

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 lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein sSOL is A method that reduces over at least one month to a line.

Embodiment 2. 2. The method of embodiment 1, wherein sSOL decreases over baseline for at least 6 months.

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

Embodiment 4. 3. The method of embodiment 2, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

Embodiment 5. 2. The method of embodiment 1, wherein sSOL is decreased for at least 20 minutes.

Embodiment 6. 2. The method of embodiment 1, wherein sSOL is 40 minutes or less.

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

Embodiment 8. 2. The method of embodiment 1, wherein the subject has insomnia.

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 at baseline for at least one month.

Embodiment 10. 10. The method of embodiment 9, wherein sSE is increased over baseline for at least 6 months.

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

Embodiment 12. 11. The method of embodiment 10, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

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

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

Embodiment 15. A method of reducing subjective wakefulness after awakening (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 less than or equal to baseline for at least one month.

Embodiment 16. 16. The method of embodiment 15, wherein sWASO decreases over baseline for at least 6 months.

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

Embodiment 18. 17. The method of embodiment 16, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

Embodiment 19. 16. The method of embodiment 15, wherein sWASO is decreased for at least 40 minutes.

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

Embodiment 21. Lemborexant or a pharmaceutically acceptable salt thereof for use in reducing subjective sleep latency (sSOL) in a subject, wherein the subject is administered 5 mg or 10 mg of lemborexant or a pharmaceutical equivalent dose thereof lemborexant, or a pharmaceutically acceptable salt thereof, wherein sSOL decreases relative to baseline for at least one month.

Embodiment 22. 22. Use according to embodiment 21, wherein sSOL decreases over baseline for at least 6 months.

Embodiment 23. 22. Use according to embodiment 21, wherein lemborexant or a salt thereof is administered to the subject for at least one month.

Embodiment 24. 23. Use according to embodiment 22, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

Embodiment 25. 22. Use according to embodiment 21, wherein sSOL is decreased by at least 20 minutes.

Embodiment 26. 22. Use according to embodiment 21, wherein the subject has insomnia.

Embodiment 27. Lemborexant or a pharmaceutically acceptable salt thereof for improving a subject's subjective sleep efficiency (sSE), wherein the subject receives 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof lemborexant, or a pharmaceutically acceptable salt thereof, comprising administering a salt wherein the sSE is increased over baseline for at least 1 month.

Embodiment 28. 28. Use according to embodiment 27, wherein the sSE is increased over baseline for at least 6 months.

Embodiment 29. 28. Use according to embodiment 27, wherein lemborexant or a salt thereof is administered to the subject for at least one month.

Embodiment 30. 29. Use according to embodiment 28, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

Embodiment 31. 28. Use according to embodiment 27, wherein sSE is improved by at least 13%.

Embodiment 32. 28. Use according to embodiment 27, wherein the subject has insomnia.

Embodiment 33. lemborexant or a pharmaceutically acceptable salt thereof for reducing subjective wakefulness (sWASO) in a subject, wherein the subject is given 5 mg or 10 mg of lemborexant or an equivalent dose thereof of a pharmaceutically acceptable lemborexant, or a pharmaceutically acceptable salt thereof, comprising administering the salt, wherein sWASO decreases relative to baseline for at least one month.

Embodiment 34. 34. Use according to embodiment 33, wherein sWASO decreases over baseline for at least 6 months.

Embodiment 35. 34. Use according to embodiment 33, wherein lemborexant or a salt thereof is administered to the subject for at least one month.

Embodiment 36. 35. Use according to embodiment 34, wherein lemborexant or a salt thereof is administered to the subject for at least 6 months.

Embodiment 37. 34. Use according to embodiment 33, wherein sWASO is reduced by at least 40 minutes.

Embodiment 38. 34. Use according to embodiment 33, wherein the subject has insomnia.

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 in the range of about 5-10 mg, The method wherein the dosage form is achievable with respect to maintaining a reduction in time to sleep onset in subjective sleep latency (sSOL) compared to placebo during treatment for at least one month.

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 in the range of about 5-10 mg, A method wherein the dosage form is achievable with respect to maintaining a reduction in time to sleep onset in subjective sleep latency (sSOL) compared to placebo during treatment through 6 months.

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 in the range of about 5-10 mg, The dosage form can be administered to the patient for at least one month, and the dosage form maintains a reduction in time to sleep onset in subjective sleep onset latency (sSOL) compared to placebo during treatment for at least one month. A method that is achievable with respect to

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 in the range of about 5-10 mg, The dosage form can be administered to the patient for 6 months, and the dosage form maintains a reduction in time to sleep onset in subjective sleep latency (sSOL) compared to placebo during treatment through 6 months. A method that is achievable with respect to

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 in the range of about 5-10 mg, A method wherein the dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) compared to placebo during treatment for at least one month.

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 in the range of about 5-10 mg, A method wherein the dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) compared to placebo during treatment through 6 months.

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 in the range of about 5-10 mg, The dosage form can be administered to the patient for at least one month, and the dosage form achieves in maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) compared to placebo during treatment for at least one month possible, how.

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 in the range of about 5-10 mg, The dosage form can be administered to the patient for 6 months, and the dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) compared to placebo during treatment through 6 months. is a method.

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 in the range of about 5-10 mg, The method wherein the dosage form is achievable with respect to maintaining improvement in wakefulness after wakefulness (sWASO) compared to placebo during treatment for at least one month.

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 in the range of about 5-10 mg, A method wherein the dosage form is achievable with respect to maintaining improvement in wake on wakefulness (sWASO) compared to placebo during treatment through 6 months.

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 in the range of about 5-10 mg, The dosage form can be administered to the patient for at least one month, and the dosage form is achievable with respect to maintaining improvement in wake on wakefulness (sWASO) compared to placebo during treatment for at least one month. .

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 in the range of about 5-10 mg, A method wherein the dosage form can be administered to a patient for 6 months and the dosage form is achievable with respect to maintaining improvement in wake on wakefulness (sWASO) compared to placebo during treatment through 6 months.

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 less than or equal to baseline versus decreasing over at least one month.

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 reduced relative to baseline and increasing over at least one month.

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 nocturnal awakening is less than or equal to baseline and decreases over at least one month.

Embodiment 54. A method of identifying a subject responsive to treatment with lemborexant or a pharmaceutically acceptable salt thereof, comprising:
a) determining a subject's pre-treatment period subjective wakefulness (sWASO);
b) if the pre-treatment period sWASO is greater than or equal to 60 minutes, administering 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof to the subject over the treatment period;
c) determining the subject's post-treatment sWASO;
d) If the post-treatment period sWASO is less than 60 minutes and the post-treatment period sWASO is at least 10 minutes less than the pre-treatment period sWASO, the subject is given 5 mg or 10 mg lemborexant or its pharmaceutically acceptable dose. administering a salt.

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

Embodiment 56. 55. The method of embodiment 54, wherein the post-treatment period sWASO is at least 30 minutes shorter than the pre-treatment period sWASO.

Embodiment 57. 55. The method of embodiment 54, wherein a pre-treatment period subjective sleep efficiency (sSE) is determined prior to administering lemborexant or a pharmaceutically acceptable salt thereof.

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

Embodiment 59. 56. The method of embodiment 55, wherein the post-treatment period sSE is improved by at least 10% relative to the pre-treatment period sSE.

Embodiment 60. 56. The method of embodiment 55, wherein the post-treatment period sSE is improved by at least 14% relative to the pre-treatment period sSE.

Embodiment 61. 55. The method of embodiment 54, wherein a pre-treatment period subjective sleep latency (sSOL) is determined prior to administering lemborexant or a pharmaceutically acceptable salt thereof.

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

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

Embodiment 64. 63. The method of embodiment 62, wherein the post-treatment period sSOL is at least 20 minutes less than the pre-treatment period sSOL.

Embodiment 65. A method of treating insomnia in a subject in need thereof, comprising:
a) determining a subject's subjective sleep onset latency (sSOL) prior to the treatment period;
b) administering to the subject an oral dosage form comprising 5 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof within 15 minutes before the subject's bedtime, wherein the subject has been at least 7 staying in bed over time, dosing;
c) determining a subject's post-treatment sSOL;
d) If post-treatment sSOL does not decrease relative to pre-treatment sSOL and the subject does not experience a serious adverse reaction, 10 mg lemborexant or an equivalent dose thereof within 15 minutes before bedtime of the subject. administering an oral dosage form comprising a pharmaceutically acceptable salt to a subject, wherein the subject remains in bed for at least 7 hours;
post-treatment period sSOL is reduced relative to pre-treatment period sSOL for at least 1 month;
The method, wherein the post-treatment period sSOL is decreased relative to the pre-treatment period sSOL by 15 minutes or more.

Embodiment 66. 66. The method of embodiment 65, wherein the post-treatment period sSOL is decreased relative to the pre-treatment period sSOL by 20 minutes or more.

Embodiment 67. 66. The method of embodiment 65, wherein the sSOL after the treatment period is 40 minutes or less.

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

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

Embodiment 70. 70. The method of embodiment 69, wherein the post-treatment period sSE is increased by 13% or more relative to the pre-treatment period sSE.

Embodiment 71. A method of treating insomnia in a subject in need thereof, comprising:
a) determining a subject's pre-treatment period subjective wakefulness (sWASO);
b) administering to the subject an oral dosage form comprising 5 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof within 15 minutes before the subject's bedtime, wherein the subject has been at least 7 staying in bed over time, dosing;
c) determining the subject's post-treatment sWASO;
d) If post-treatment sSOL does not decrease relative to pre-treatment sWASO and the subject does not experience a serious adverse reaction, 10 mg lemborexant or an equivalent dose thereof within 15 minutes prior to bedtime for the subject. administering an oral dosage form comprising a pharmaceutically acceptable salt to a subject, wherein the subject remains in bed for at least 7 hours;
post-treatment period sWASO decreased relative to pre-treatment period sWASO for at least 1 month;
The method, wherein the post-treatment period sWASO is reduced relative to the pre-treatment period sWASO by at least 29 minutes.

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

Embodiment 7. A method of treating insomnia comprising orally administering a dosage form comprising 3.5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, comprising:
Oral administration of a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to the patient no more than once per night and within a few minutes before bedtime, with at least 7 hours remaining until the scheduled wake-up time. , if the 5 mg dose is well tolerated but is not effective, then the dose can 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 latency (sSOL) during treatment for at least one month;
Method, wherein sSOL is decreased by at least 15 minutes relative to baseline.

Embodiment 7 A method of treating insomnia comprising orally administering a dosage form comprising 4.5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, comprising:
Oral administration of a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to the patient no more than once per night and within a few minutes before bedtime, with at least 7 hours remaining until the scheduled wake-up time. , if the 5 mg dose is well tolerated but is not effective, then the dose can be increased to 10 mg once daily;
the dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) during treatment for at least one month;
Method, wherein sSE is improved by at least 4% over baseline.

Embodiment 7 A method of 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, comprising:
Oral administration of a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to the patient no more than once per night and within a few minutes before bedtime, with at least 7 hours remaining until the scheduled wake-up time. , if the 5 mg dose is well tolerated but is not effective, then the dose can be increased to 10 mg once daily;
the dosage form is achievable with respect to maintaining improvement in subjective wakefulness after treatment (sWASO) for at least one month;
Method, wherein sWASO is decreased by at least 29 minutes relative to baseline.

Embodiment 76. A method of 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, comprising:
orally administering to the patient no more than once per night, immediately prior to bedtime, a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof with at least 7 hours remaining until the scheduled wake-up time;
The daily dose may be increased to 10 mg based on clinical response and tolerability, and the dosage form maintains a reduction in time to sleep onset in subjective sleep latency (sSOL) during treatment for at least 1 month. A method that is achievable for doing.

Embodiment 77. 77. The method of embodiment 76, wherein the dosage form is achievable with respect to maintaining a reduction in time to sleep onset in subjective sleep latency (sSOL) during treatment for at least 6 months.

Embodiment 78. 77. The method of embodiment 76, wherein the dosage form can be administered to the patient for at least one month.

Embodiment 79. 77. The method of embodiment 76, wherein the dosage form can be administered to the patient for at least 6 months.

Embodiment 80. 77. The method of embodiment 76, wherein sSOL is decreased by at least 15 minutes relative to baseline.

Embodiment 8 A method of treating insomnia comprising orally administering a dosage form comprising 1.5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, comprising:
orally administering to the patient no more than once per night, immediately prior to bedtime, a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof with at least 7 hours remaining until the scheduled 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 sleep efficiency improvement in subjective sleep efficiency (sSE) during treatment for at least one month.

Embodiment 82. 82. The method of embodiment 81, wherein the dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) during treatment for at least one month.

Embodiment 83. 82. The method of embodiment 81, wherein the dosage form can be administered to the patient for at least one month.

Embodiment 84. 82. The method of embodiment 81, wherein the dosage form can be administered to the patient for at least 6 months.

Embodiment 85. 82. The method of embodiment 81, wherein sSE is improved by at least 4% over baseline.

Embodiment 8 A method of treating insomnia comprising orally administering a dosage form comprising 6.5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, comprising:
orally administering to the patient no more than once per night, immediately prior to bedtime, a 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof with at least 7 hours remaining until the scheduled 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 improvement in subjective wakefulness after treatment (sWASO) for at least one month.

Embodiment 87. 87. The method of embodiment 86, wherein the dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) during treatment for at least one month.

Embodiment 88. 87. The method of embodiment 86, wherein the dosage form can be administered to the patient for at least one month.

Embodiment 89. 87. The method of embodiment 86, wherein the dosage form can be administered to the patient for at least 6 months.

Embodiment 90. 87. The method of embodiment 86, wherein sWASO is decreased by at least 29 minutes relative to baseline.

The following examples are provided so that the disclosure provided herein may be more fully understood. It should be understood that these examples are for illustrative purposes only and should not be construed as limiting this disclosure in any way.

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

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

EQ-5D-3L - Health-Related Quality of Life Assessment: An instrument that can be used in clinical and economic judgments of health care and to collect data on quality of life and preferences/availability. The instrument includes questions regarding mobility, self-care, daily activities, pain/discomfort and anxiety/depression and scores from 0 (“worst health imaginable”) to 100 (“best health imaginable”). Includes a visual analogue scale of up to.

LPS-sustained sleep latency: minutes from lights out to the first of 20 consecutive epochs of non-awake state.

PGI-Insomnia-Patient Global Impression Rating-Insomnia: A self-report rating asking how the subject feels about the effect of study medication on their sleep compared to their sleep prior to entering the study. PGI-Insomnia included 3 items (a: improved/worse sleep, b: decreased/increased time to fall asleep, and c: increased/decreased TST) and different 3-point scales of study drug effect. 1 item (1=good pharmacotherapeutic effect, 2=neither good nor bad pharmacotherapeutic effect, 3=bad pharmacotherapeutic effect) and the last item (medication: 1=too strong, 2=just right, 3 = too weak). Each item was reported separately.

SAE - Serious Adverse Event

SDSB - Sleep Disorder Screening Battery

SE-Sleep Efficiency: Ratio of time spent asleep per total bedtime, calculated as TST/distance from lights off to lights on.

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

sSOL - subjective sleep onset latency: an estimate of the number of minutes from when the subject attempted to fall asleep to sleep onset.

sTST - Subjective Total Sleep Time: Derived number of sleep minutes from sleep onset to the time the subject stopped trying to sleep for the night.

sWASO—Subjective Nocturnal Awakening: The sum of estimated nocturnal wakefulness minutes after the first sleep onset until the time the subject stopped trying to sleep that night, operationalized as the time the subject left the bed for the day.

T-BWSQ - Tyrer's Benzodiazepine Withdrawal Symptom Questionnaire: A questionnaire designed to assess withdrawal symptoms associated with study drug discontinuation. Tyrer, P.; et al. "The benzodiazepine withdrawal symptom questionnaire."J. Affect. Disord. 1990; 19(1):53-61.

TEAEs - treatment-emergent adverse events

TST - total sleep time: number of minutes of sleep from sleep onset to end of wakefulness.

WASO - Mid-Awakening: Awakening minutes from onset of sustained sleep to lighting.

WASO2H: Late Night Awakening: Awakening minutes during the interval from 240 minutes after lights out to lights on.

WPAI-GH - Work Productivity and Disability Questionnaire - General Health: Collects data on absenteeism and presenteeism. This scale contains 6 items, which are used to calculate 4 scores. The results are expressed as failure rates, with higher numbers implying greater failure and lower productivity. The four scores include: (1) percent absenteeism for health reasons; (2) percent rate of disability at work for health reasons; (3) percent overall disability rate for health reasons; 4) Includes percent disability rate for health reasons.

Example 1. Treatment of Subjects with Insomnia Disorders Subjects, both male and female, aged 18 and older, approximately 40% of the population aged 65 and older, were screened for treatment eligibility. 971 subjects were randomized to treatment, however, only 949 subjects are in the full analysis set population. Demographic information of the subject population is presented in Table 1.

The study consisted of a pre-randomization phase and a randomization phase.

Pre-randomization Phase The pre-randomization phase consisted of three periods: screening period, run-in period and baseline period.

Screening Period The Screening Period began within 35 days prior to subject randomization. If a subject is evaluated based on the eligibility criteria and other assessments (e.g., the Sleep Disorders Screening Battery) and is deemed eligible, how will the subject keep a sleep diary, discussed herein? I was instructed as to whether I should report measurements of sleep parameters that Subjects then proceeded to the run-in period.

Run-in Period The run-in period began when eligible subjects received a placebo tablet each night just prior to bedtime for at least 13 nights. During the run-in period, subjects were required to stay in bed for at least 7 hours each night and maintain a regular bedtime.

Baseline Period After treatment with placebo during the run-in period, subjects will be evaluated (e.g., insomnia severity index, clinical blood and urine tests, vital signs, weight and electrocardiogram) and, if still eligible, the randomization phase. proceeded to

Randomization Phase The randomization phase consisted of two periods: Treatment Period 1 and Treatment Period 2. The randomization phase lasted 12 months.

Subjects were randomized in a double-blind fashion to receive either placebo, 5 mg lemborexant or 10 mg lemborexant (approximately 1:1:1 randomization). All subjects underwent routine safety monitoring during the study, including evaluation of treatment-emergent adverse events, 12-lead electrocardiogram, vital signs, body weight, and clinical hematology and blood chemistries. Suicidality was assessed using the eC-SSRS.

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 waking up. Subjects underwent clinician evaluations at 1 month, 2 months, 3 months and 6 months after the start of Treatment Period 1. The following evaluations were made.

Month 1 Evaluation: A standard safety evaluation was performed on the subject. Blood samples were taken to determine plasma concentrations of lemborexant and its metabolites and ISI, FSS, PGI-Insomnia, EQ-5D-3L and eC-SSR were completed.

Month 2 Evaluation: A standard safety evaluation was performed on the subject.

Month 3 Assessment: All assessments performed at the Month 1 assessment were repeated.

Month 6 Assessment: All assessments performed at the Month 1 Assessment were repeated and subject completed the WPAI-GH.

After completion of the 6-month evaluation, treatment period 1 ended and treatment period 2 began.

Treatment period 2
At the end of the Treatment Period 1 Month 2 Evaluation (Treatment Period 2 Baseline), subjects who received placebo in Treatment Period 1 underwent a second randomization to receive either 5 mg or 10 mg lemborexant. was to be administered. Subjects who received lemborexant during Treatment Period 1 continued to receive the same dose of lemborexant.

During Treatment Period 2, subjects continued to complete sleep diaries as during Treatment Period 1. Subjects were evaluated during the 9-month and 12-month evaluations. At 7, 8, 10 and 11 months, the clinician discussed treatment by telephone (eg, sleep diary, concomitant medications, adverse events).

During the 9 and 12-month evaluations, the safety and tolerability of lemborexant were evaluated, the ec-SSR was completed, urine drug tests were performed, and subjects were enrolled in ISI, FSS, EQ-5D-3L, PGI - Insomnia and WPAI-GH were also completed. A blood sample (for pharmacokinetic analysis) was also collected.

Early Medication Discontinuation Subjects who prematurely discontinued study drug at any time after the start of the randomization phase were asked to return to the clinician within 7 days of discontinuation. These subjects were encouraged to continue to complete all study evaluations (except blood sample collection), including sleep diaries.

Follow-up period The follow-up period began at the end of treatment period 2. The subject discontinued taking study medication, however, entry into their sleep diary each morning continued until the end of study visit.

End of Study Visit Subjects were evaluated 14-18 days after completion of Treatment Period 2. In addition to standard safety assessments and completion of the eC-SSRS, a urine drug test was performed, a T-BWSQ was administered, and a sleep diary was collected.

Subject Population Inclusion Criteria Subjects were eligible to participate in the study if they met all of the following inclusion criteria:
- Males and females 18 years of age or older at the time of submission of informed consent.
• Met the criteria for Insomnia Disorders of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM 5):
i. Complains of nocturnal sleep in the form of difficulty falling asleep, difficulty staying asleep, and/or waking up earlier than desired despite having a good opportunity to sleep;
ii. frequency of complaints 3 or more times a week;
iii. the duration of the complaint is 3 months or more;
iv. with complaints of daytime dysfunction.
• At Screening: Experiencing sSOL of 30 minutes or longer for at least 3 nights/week in the last 4 weeks and/or sWASO of 60 minutes or longer for at least 3 nights/week in the last 4 weeks.
• At Screening: Reported a regular bedtime of 7-9 hours (whether sleeping or trying to sleep).
At first screening visit (Visit 1) and second screening visit (Visit 2a): Regular bedtime from 21:00 to 01:00 (defined as the time the subject attempts to sleep) and from 05:00 to 10:00: 00 regular wake-up time (defined as the time the subject left the bed for the day) was reported.
- ISI score ≥ 15 at screening and study baseline.
At Second Screening Visit (Visit 2a): 7 nights as determined from sleep diary responses completed on at least 7 consecutive mornings (minimum 5 mornings out of 7 for eligibility) Confirmation of current insomnia, such as sSOL > 30 minutes on at least 3 of the 7 nights and/or sWASO > 60 minutes on at least 3 of the 7 nights.
At Second Screening Visit (Visit 2a): Subject has 7-10 hours, as determined from sleep diary responses completed in the morning for a minimum of 7 consecutive days between the first and second Screening Visits Confirmation of regular bedtime and wake-up time, including having a regular bedtime (whether sleeping or trying to sleep).
At the 2nd Screening Visit (Visit 2a): Staying in bed for less than 7 hours as determined from sleep diary responses completed in the mornings of the 7 days between the 1st and 2nd Screening Visits. Confirmation that the duration of bedtime is sufficient, such as no more than 2 nights longer than 10 hours.
At Baseline (Visit 3a): sSOL > 30 min on at least 3 of the 7 nights and/or 7 nights as determined from sleep diary responses for the last 7 nights of the run-in period Re-examination of insomnia symptoms, such as sWASO greater than 60 minutes on at least 3 of the nights.
At Baseline (Visit 3a): For the last 7 nights of the run-in period, the subjects had a regular bedtime of 7-10 hours (whether they were asleep or trying to sleep). Confirmation of bedtime and wake-up time.
At Baseline (Visit 3a): Regular bedtime from 21:00 to 01:00 (defined as the time the subject attempted to sleep) and from 05:00 to 10:00 for the last 7 nights of the run-in period Reconfirmation of the regular wake-up time (defined as the time the subject left the bed for the day).
• Willingness and ability to comply with all aspects of the protocol, including going to bed for at least 7 hours each night.
• Subject is unwilling to initiate behavioral therapy or other treatment programs for insomnia while participating in this study.

Exclusion Criteria Subjects were not eligible to participate in the study if they met any of the following exclusion criteria:
At that time, sleep-related breathing disorders including obstructive sleep apnea (with or without continuous positive airway pressure (CPAP) therapy), periodic limb movement disorder, restless leg syndrome, circadian rhythm sleep Diagnosis of Disorder or Narcolepsy or SDSB Exclusion Score as follows:
i. STOPBang score of 5 or greater;
ii. an IRLS score of 16 or greater; and iii. had an ESS score greater than 15.
- Reported symptoms that may be associated with narcolepsy that indicated that the investigator's clinical opinion required referral for diagnostic evaluation of whether narcolepsy was present.
• Reported having sleep-related violent behavior or somnambulism or any other compound-related behavior such as making a phone call in sleep or preparing and eating a meal.
For subjects who underwent diagnostic polysomnographic analysis within 1 year prior to informed consent:
i. Age 18-64 years: Apnea hypopnea index greater than 10 or periodic limb movement index with arousal greater than 10.
ii. 65 years and older: Apnea hypopnea index greater than 15 or periodic limb movement index with arousal greater than 15.
- Beck Depression Rating Scale-II (BDI-II) score greater than 19 at screening.
- Beck Anxiety Assessment Scale (BAI) score greater than 15 at Screening.
Habitual napping more than 3 times a week.
• Women who are lactating or pregnant at screening or at study baseline (as documented by positive serum β-human chorionic gonadotropin [β-hCG]). A separate baseline evaluation was required if a negative pregnancy screening test was obtained ≥72 hours prior to the first dose of study drug.
- A woman of childbearing potential,
i. Subjects who had unprotected sexual intercourse within 30 days prior to study entry or highly effective methods of contraception (e.g., total abstinence, intrauterine devices, contraceptive implants, injectable contraceptives) throughout the study period or for 28 days after discontinuation of study drug. , oral contraceptives, or having a vasectomized partner with confirmed azoospermia). Cyclic abstinence (eg, calendar, ovulatory, symptomatic, postovulatory) and extravaginal ejaculation are unacceptable methods of contraception.
ii. Subjects who were abstinent at the time and did not agree to use highly effective methods (as described above) or abstain from sexual activity during the study period and for 28 days after discontinuation of study drug.
iii. Subjects who are using hormonal contraceptives but have not continued on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and who have not consented to use the same contraceptive during the study and for 28 days after discontinuing study drug. person.
iv. Note: All women were postmenopausal (defined as having been amenorrhea for at least 12 consecutive months, of appropriate age, and postmenopausal with no other known or suspected cause) or sterilized. considered fertile unless (ie bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all performed at least 1 month prior to dosing).
Excessive caffeine use or habitual consumption of caffeine-containing beverages after 18:00 and café after 18:00 during their participation in the study that, in the investigator's opinion, contributes to insomnia in the subject I had no intention of stopping the Inn. Ingestion of high doses of caffeine (significantly exceeding 250 mg) in the last 3 months and the following symptoms: restlessness, irritability, irritability, insomnia, hot flushes, diuresis, gastrointestinal disturbances, muscle spasms, ramblings. If there were symptoms that would have met the DSM-5 criteria for caffeine intoxication, including 5 or more of the following: stream of thoughts and speech, tachycardia or cardiac arrhythmia, periods of high energy or psychomotor agitation; Subject excluded. Conditions that cause distress or impairment in social, occupational and other forms of functioning and that have not been linked to other substances, mental disorders or medical conditions are excluded.
- A history of drug or alcohol dependence or abuse within the past approximately two years.
Reported habitual intake of >14 alcohol-containing drinks per week (women) or >21 alcohol-containing drinks per week (men), or reduced alcohol intake to ≤2 drinks per day during their participation in the study There was no intention to limit or stop drinking within 3 hours before bedtime.
• Known to be human immunodeficiency virus (HIV) positive • Active viral hepatitis (B or C) as demonstrated by positive sera at screening.
QT/QT interval (QTcF) interval prolongation (QTcF) corrected by Fridericia's formula as documented by repeat ECG at screening (repeated only if initial ECG showed QTcF interval >450 ms) >450 ms).
Any clinically significant disease at that time (e.g., cardiac disease; respiratory disease, including chronic obstructive pulmonary disease, acute and/or severe respiratory depression; severe liver failure; gastrointestinal disease; severe renal impairment, including neurological disease [including subjects who lack capacity and/or whose cognitive decline indicates disorientation to person/place/time and/or situation] or psychiatric disease or malignancy within the last 5 years [Excluding appropriately treated basal cell carcinoma]) had chronic pain that, in the opinion of the investigator, may affect the subject's safety or interfere with study evaluation. Subjects for whom sedatives would have been contraindicated for safety reasons due to their occupation or activity were also excluded.
Intercurrent nocturnal polyuria requiring frequent getting out of bed to go to the toilet during the night.
Any history of medical or psychiatric conditions that, in the Investigator's opinion, may have affected the subject's safety or interfered with the study evaluation.
Any suicidal ideation with or without planning at Screening or Study Baseline or within 6 months of Study Baseline (i.e., 'Yes' to Question 4 or 5 in the Suicidal Ideation section of the eC-SSRS) answer).
• Voluntary suicidal behavior in the last 10 years (according to the suicidal behavior section of the eCSSRS).
- Major surgery was scheduled during the study.
• Concomitant medication with any prohibited prescription or over-the-counter drug for 1 week prior to the first dose of study drug or for 5 half-lives, whichever is longer (run-in period).
Use any modality of insomnia treatment, including cognitive-behavioral therapy or marijuana, for 1 week prior to the first dose of study drug or for 5 half-lives, whichever is longer (run-in period).
• Treatment failure (efficacy or safety) with suvorexant after adequate dose and adequate duration of treatment, in the investigator's opinion.
• Transmerridional movement across more than 3 time zones in the 2 weeks prior to screening or between screening and baseline.
- Had a positive drug test at screening, induction or baseline, or was unwilling to abstain from recreational drug use during the study.
• Hypersensitivity to study drug or any excipient.
• Was enrolled in another clinical trial at the time or used any investigational drug or device for 30 days prior to informed consent or 5 half-lives, whichever is longer.
Have previously participated in any lemborexant clinical trial.

Study Medication Subjects received a 5 mg lemborexant tablet, a 10 mg lemborexant tablet, or a lemborexant-matched placebo tablet.

Study Endpoints Primary Endpoint The primary endpoint was the mean change from study baseline in subjective sleep latency at 6 months.

Secondary Endpoints of Interest The study had two secondary endpoints of interest. The first key secondary endpoint was the mean change from study baseline in subjective sleep efficiency at 6 months. A second key secondary endpoint was the mean change from study baseline in subjective nocturnal alertness at 6 months.

Additional Secondary Endpoints In addition to the study endpoints described above, the study included several additional secondary endpoints:
- Subjective sleep onset latency, subjective sleep efficiency, subjective nocturnal awakening, and subjective total sleep time at the start of treatment (mean value for 7 nights after the first dose in period 1), 1 month and 3 months Average change from line.
• Mean change from study baseline in subjective total sleep time at 6 months.
• Change from study baseline in daytime functioning at 1, 3 and 6 months, assessed as a 4-item sum score for daytime functioning on the Insomnia Severity Index.

Safety endpoints The safety endpoints of the study included: (1) compared to placebo (during treatment period 1), and (2) in subjects exposed to lemborexant for 3, 6, 9 and 12 months, The safety and tolerability of lemborexant were included.

result

The primary efficacy endpoint was the change from study baseline in mean subjective sleep onset latency (estimated number of minutes from subject's attempt to fall asleep to sleep onset). As shown in Table 2, the mean subjective sleep onset values for all treatment groups were shorter than study baseline, and subjects treated with lemborexant had higher subjective sleep onset latencies at equivalent time points than subjects treated with placebo. was shortened. See also FIGS. 1 and 2. FIG.

As shown in Table 3, mean subjective sleep efficiency values for all treatment groups increased relative to study baseline, with subjects treated with lemborexant having higher subjective sleep efficiency than placebo-treated subjects at equivalent time points. Greatly increased sleep efficiency. See also FIGS.

As shown in Table 4, the mean subjective nocturnal wakefulness for all treatment groups decreased relative to study baseline, with subjects treated with lemborexant having higher subjective nocturnal alertness at equivalent time points than subjects treated with placebo. Midway awakening average value decreased significantly. See also FIGS.

As shown in Table 5, mean subjective total sleep duration for all treatment groups increased relative to study baseline, with subjects treated with lemborexant having higher subjective sleep duration than placebo-treated subjects at equivalent time points. target total sleep time increased significantly.

As shown in Tables 6 and 7, mean Insomnia Severity Index scores for all treatment groups decreased relative to study baseline, with subjects treated with lemborexant having an equivalent Insomnia Severity Index score at time point decreased significantly.

As shown in Table 8, mean values of items related to sleep quality and morning sleepiness (Insomnia Severity Index) were higher in lemborexant-treated subjects compared to placebo-treated subjects at 6 months. significantly improved.

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

Example 2. Treatment of Subjects with Insomnia Disorders Both male and female subjects 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.

The study consisted of a pre-randomization phase and a randomization phase.

Pre-randomization Phase The pre-randomization phase consisted of three periods: screening period, run-in period and baseline period.

Screening Period The Screening Period began within 35 days prior to subject randomization. Where informed consent was obtained, a medical history, psychiatric history, and sleep history interview was conducted, and this interview required that the subject met the diagnostic criteria for insomnia disorder, and that the subject had difficulty maintaining sleep or Confirmation of complaints of early morning awakening or both was included. Screening assessments performed were the Insomnia Sleep Index (ISI), Epworth Sleepiness Scale (ESS), STOPBang Sleep Apnea Questionnaire, International Restless Leg Scale (IRLS) and Munich Parasomnia Scale (MUPS). rice field. These assessments are collectively referred to as the sleep disorder screening battery.

A sleep diary was distributed to the subjects and instructed how to record the items. After subjects completed a sleep diary each morning for 7 consecutive days, subjects attended a second clinical meeting 10-17 days prior to the randomization phase, if the subject was still eligible to participate in the study. did. Subjects were then fitted with a polysomnograph and instructed on how to complete the Postural Stability Assessment and the Cognitive Performance Assessment Battery. Subjects then underwent 8-hour polysomnographic recordings. Postural stability assessments and cognitive assessment batteries were performed on subjects within 5 minutes of awakening.

If the subject was still eligible to participate, the subject was distributed a placebo tablet and the run-in period began.

Run-in Period The run-in period began when eligible subjects were dispensed placebo tablets and continued through Day 1 of the Baseline Period. During the run-in period, subjects took placebo each night within 5 minutes before bedtime and remained in bed for at least 7 hours.

Subjects' eligibility was reviewed again once they had completed sleep diary entries for at least consecutive mornings during this period. If eligible, subjects returned for the first of two nights on which an overnight polysomnographic examination was to be performed. Insomnia Severity Index, FSS and EQ-5D-3L were also assessed. Subjects were then administered study drug within 5 minutes of their scheduled bedtime. Subjects then underwent an 8-hour polysomnogram. After awakening, postural and cognitive battery assessments were performed and a sleep diary was completed. Subjects were then free to leave the house for the day and returned later for another night.

Subjects were then allowed to go home and took study medication according to clinic procedures. After a minimum of two nights, the run-in period ended.

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

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

Treatment Period The treatment period lasted for 31 days. Subjects were randomized in a double-blind fashion to receive placebo, tablets containing 5 mg lemborexant, tablets containing 10 mg lemborexant, or tablets containing 6.25 mg zolpidem ER. .

Study drug was administered within 5 minutes of the subject's average habitual bedtime and overnight polysomnographic recording was initiated. Postural stability and cognitive performance were assessed the following morning (Day 2) at the completion of the recording. Subjects returned to the clinic on the evening of Day 2, blood samples were taken prior to administration of study drug, and then study drug was administered within 5 minutes of the subject's average habitual bedtime. Again, polysomnographic recording was initiated. Postural stability and cognitive performance were assessed the following morning (Day 3). A blood sample was also taken.

Subjects then completed their own sleep diaries. eC-SSRS was administered. Within 1.5 hours of waking, subjects scored their level of sleepiness for the morning. Subjects were allowed to leave the hospital if the clinician deemed them safe to do so.

After returning home, subjects took study medication each night before bedtime and completed their sleep diary within 1 hour of waking up.

On Day 29, the subject returned to the hospital. Study drug was administered within 5 minutes of the subject's average habitual bedtime and polysomnographic recording was performed. Postural stability and cognitive performance were assessed the following morning (day 30). 1.5 hours after the wake-up time, subjects scored their level of sleepiness for the morning.

The subject returned to the hospital on the evening of Day 30. A pre-dose blood sample was taken and study drug was administered again within 5 minutes of the subject's average habitual bedtime. Polysomnographic recording was initiated. The following morning (day 31), postural stability and cognitive performance were assessed and blood samples were taken. ISI, FSS, EQ-5D-3L and PGI-Insomnia were administered. Blood and urine samples were collected for routine safety evaluation. An electrocardiogram was performed and vital signs and weight were assessed. Subjects then underwent eC-SSRS. At 1.5 hours after the wake-up time, subjects rated their sleepiness level for the morning.

Follow-up Period The follow-up period began when subjects were discharged from the hospital at the end of the treatment period. The subject stopped taking study medication, but continued to complete their sleep diary each morning until the end of the study visit.

14-18 days after completing the treatment period, the subject returned for the end of the study visit. T-BWSQ and eC-SSRS were performed and routine safety assessments were performed.

Study Discontinuation Subjects who discontinued prematurely from study drug should return as soon as feasible after discontinuing study drug. If a subject discontinues due to an adverse event, the adverse event must be followed until resolution or 2 weeks, whichever comes first. In addition, subjects who discontinued early underwent a urine drug test.

Study Medication Subjects received 2 tablets daily according to the treatment arm in which they were randomized:
• 5 mg lemborexant treatment arm: 1 zolpidem ER-matched placebo tablet and 1 lemborexant 5 mg tablet.
• 10 mg lemborexant treatment group: 1 zolpidem ER-matched placebo tablet and 1 lemborexant 10 mg tablet.
• Zolpidem ER 6.25 mg: 1 Zolpidem ER 6.25 mg tablet and 1 placebo tablet corresponding to lemborexant.
- Placebo: 1 placebo tablet corresponding to zolpidem ER and 1 placebo tablet corresponding to lemborexant.

Study Endpoints The study had a primary endpoint, several important secondary endpoints and several additional secondary endpoints.

Primary Endpoint The primary endpoint was to determine the change from baseline in mean sustained sleep latency on Days 29 and 30 for 5 mg or 10 mg lemborexant compared to placebo.

Key Secondary Endpoints One key secondary endpoint was the change from baseline in mean sleep efficiency on days 29 and 30 after administration of 5 mg or 10 mg lemborexant compared to placebo. was to decide

Another key secondary endpoint was to determine the change from baseline in mean nocturnal awakening on days 29 and 30 after administration of 5 mg or 10 mg lemborexant compared to placebo. rice field.

Another key secondary endpoint was the average late-night nocturnal awakening on days 29 and 30 after administration of 5 mg or 10 mg lemborexant compared with administration of 6.25 mg zolpidem ER at baseline It was to determine the change from the line.

An exemplary additional secondary endpoint is the change from baseline in mean sway units on the Postural Stability Test on days 2 and 3 after administration of 5 mg or 10 mg lemborexant compared to zolpidem. be.

Inclusion Criteria Subjects were eligible to participate in the study if they met all of the following inclusion criteria:
• Men aged 65 or older or women aged 55 or older at the time of informed consent.
• Met the criteria for Insomnia Disorders of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition:
i. They have difficulty staying asleep and/or complain of nocturnal sleep in the form of waking up earlier in the morning than they would like, despite having ample opportunity to sleep.
ii. The frequency of complaints is 3 or more times a week.
iii. The period of complaint is more than 3 months.
iv. with complaints of daytime dysfunction.
• At Screening: Experiencing sWASO for at least 3 nights per week, typically more than 60 minutes, in the last 4 weeks.
• At Screening: Reported a regular bedtime of 7-9 hours (whether sleeping or trying to sleep).
• At Screening: Reported habitual bedtime from 21:00 to 24:00 (defined as the time the subject attempted to sleep) and habitual wake up time from 05:00 to 09:00.
• At screening and at admission procedure before first polysomnography during run-in period: ISI score ≥ 13;
- sWASO of 60 on at least 3 of the 7 nights as determined from sleep diary responses for the 7 mornings immediately prior to the second screening visit (minimum of 5 mornings of the 7 days for eligibility) Confirmation of insomnia at the time, e.g.
Bedtime (defined as the time the subject attempted to fall asleep) or wakeup time (defined as the time the subject left the bed that day, as determined from responses on the morning sleep diary for the 7 days immediately prior to the second screening visit regular bedtime, i.e., no more than 2 nights deviated by more than 1 hour from the mean habitual bedtime or median habitual waking time, respectively, calculated from the sleep diary items at screening. And confirmation of wake-up time.
- Staying in bed for less than 7 hours or 2 or fewer nights longer than 10 hours, as determined from answers on the morning sleep diary for the 7 days immediately prior to the second screening visit Make sure you have enough time.
・ During the introduction period: Insomnia symptoms, such as sWASO of 60 minutes or more on at least 3 of the 7 nights, as determined from responses on the morning sleep diary for the 7 days immediately before the first polysomnography during the introduction period reconfirmation.
• During the run-in period: Reconfirm regular bedtime and wake-up times as defined above.
• During the introductory period: reconfirmation of adequate bed duration as defined above.
• During the run-in period: Objective evidence of insomnia by polysomnography as follows: Two consecutive polysomnographic WASO mean values of 60 minutes or more and not less than 45 minutes on any night.
• Willingness and ability to comply with all aspects of the protocol, including going to bed for at least 7 hours each night.
• Subject is unwilling to initiate behavioral therapy or other treatment programs for insomnia while participating in this study.

Exclusion Criteria Subjects were not eligible to participate in the study if they met any of the following exclusion criteria:
At that time, sleep-related breathing disorder (including obstructive sleep apnea with or without continuous positive airway pressure therapy), periodic limb movement disorder, restless leg syndrome, circadian rhythm sleep disorder or narcolepsy Exclusion scores on screening instruments that exclude diagnoses or symptoms of certain sleep disorders other than insomnia, such as:
i. STOPBang Sleep Apnea Questionnaire score of 5 or greater ii. IRLS score of 16 or greater iii. ESS score greater than 15 (scores 11-15 require excessive daytime sleepiness documented in the subject's medical history)
had
- Reported symptoms that may be associated with narcolepsy that indicated that the investigator's clinical opinion required referral for diagnostic evaluation of whether narcolepsy was present.
- On the MUPS, an item corresponding to a history of sleepwalking sickness was approved, or sleep-related violent behavior, sleepwalking sickness or another parasomnia that, in the opinion of the investigator, made the subject unsuitable for the study A history of disease symptoms was reported.
• Apnea hypopnea index greater than 15 or arousal periodic limb movement index greater than 15 as measured by PSG at the 2nd Screening Visit.
- Beck Depression Rating Scale-II (BDI-II) score greater than 19 at screening.
- Beck Anxiety Assessment Scale (BAI) score greater than 15 at Screening.
Habitual daytime naps more than 3 times a week.
・The patient was a woman of childbearing potential. (Note: All women were postmenopausal (defined as having been amenorrhea for at least 12 consecutive months, in the appropriate age group, and postmenopausal with no other known or suspected cause) or contraceptive. Patients were considered fertile unless they had had surgery (ie bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all at least 1 month prior to dosing).
Excessive caffeine use or habitual consumption of caffeine-containing beverages after 18:00 and café after 18:00 during their participation in the study that, in the investigator's opinion, contributes to insomnia in the subject I had no intention of stopping the Inn.
- A history of drug or alcohol dependence or abuse within the past approximately two years.
Reported habitual consumption of >14 alcohol-containing drinks per week (women) or >21 alcohol-containing drinks per week (men), or habitually consumed alcohol within 3 hours before bedtime and voluntarily were unwilling to limit their alcohol intake to no more than 2 drinks per day or to stop drinking within 3 hours before bedtime during their participation in the study.
・The patient was found to be human immunodeficiency virus positive.
• Active viral hepatitis (B or C) as demonstrated by positive sera at screening.
- QT/QT interval (QTcF) interval corrected for heart rate by Fridericia's formula, as demonstrated by repeat ECG at screening (repeated only if initial ECG showed QTCF interval >450 ms) Prolongation (QTcf>450 ms).
- Clinically significant disease at the time (e.g., cardiac disease; respiratory disease, including chronic obstructive pulmonary disease, acute and/or severe respiratory depression; gastrointestinal disease, including severe hepatic impairment; severe renal function) renal disease, including disability; neurological disease, including myasthenia gravis; psychiatric disease; Had chronic pain that may have affected safety or interfered with study evaluations, including ability to perform cognitive PAB tasks. Subjects for whom sedatives would have been contraindicated for safety reasons due to their occupation or activity were also excluded.
Intercurrent nocturnal polyuria requiring frequent getting out of bed to go to the toilet during the night.
Any history of medical or psychiatric conditions that, in the investigator's opinion, might have affected the subject's safety or interfered with the study evaluation, including the ability to perform the PAB .
Any suicidal ideation with or without planning at or within 6 months prior to the eC-SSRS in the pre-randomization phase (i.e., question no. answer “yes”).
• Voluntary suicidal behavior in the last 10 years (according to the suicidal behavior section of the eC-SSRS).
- Major surgery was scheduled during the study.
• Concomitant medication with any prohibited prescription or over-the-counter drug for 1 week prior to the first dose of study drug or for 5 half-lives, whichever is longer (run-in period).
Use any modality of insomnia treatment, including cognitive-behavioral therapy or marijuana, for 1 week prior to the first dose of study drug or for 5 half-lives, whichever is longer (run-in period).
• Treatment failure (efficacy or safety) with suvorexant after adequate dose and adequate duration of treatment, in the investigator's opinion.
• Trans-meridian travel across more than 3 time zones in the 2 weeks prior to screening or between screening and baseline or planned travel across more than 3 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 study drug (lemborexant or zolpidem) or its excipients.
• Was enrolled in another clinical trial at the time or used any investigational drug or device for 30 days prior to informed consent or 5 half-lives, whichever is longer.
Have previously participated in any lemborexant clinical trial.

result

As shown in Table 13, mean sustained sleep latency decreased for all lemborexant-treated groups relative to baseline, placebo, and zolpidem.

As shown in Table 14, mean sleep efficiency values increased for all lemborexant-treated groups relative to baseline, placebo-treated groups, and zolpidem-treated groups.

As shown in Table 15, mean nocturnal awakenings decreased for all lemborexant-treated groups relative to baseline, placebo- and zolpidem-treated groups.

As shown in Table 16, mean late-night nocturnal awakenings decreased for all lemborexant-treated groups relative to baseline, placebo- and zolpidem-treated groups.

As shown in Table 17, mean total sleep time increased for all lemborexant-treated groups relative to baseline, placebo-treated groups, and zolpidem-treated groups.

As shown in Table 18, mean subjective sleep onset latency decreased for all lemborexant-treated groups relative to baseline, placebo-treated and zolpidem-treated groups.

As shown in Table 19, mean subjective sleep efficiency values increased for the 10 mg lemborexant-treated group versus baseline, placebo- and zolpidem-treated groups.

As shown in Table 20, mean subjective nocturnal awakenings decreased for the 10 mg lemborexant treatment group versus baseline, placebo and zolpidem treatment groups.

As shown in Table 21, mean subjective total wake time increased for the 10 mg lemborexant-treated group versus baseline, placebo- and zolpidem-treated groups.

As shown in Table 22, mean Insomnia Severity Index total scores decreased for the lemborexant-treated group versus baseline and placebo-treated groups.

As shown in Table 23, mean Insomnia Severity Index daytime scores decreased for the lemborexant-treated group versus baseline and placebo-treated groups.

As shown in Table 24, body sway was reduced for all lemborexant-treated groups relative to baseline, placebo-treated and zolpidem-treated groups. Lemborexant had no significant effect on postural stability when compared to placebo.

As shown in Table 27, administration of lemborexant did not interfere with the subject's ability to be awakened by external stimuli.

As shown in Table 28, treatment with lemborexant (both doses) reduced sleep re-entry latency to a greater extent than treatment with placebo and zolpidem.

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

FIGS. 11A-11D show that after the first two nights of treatment, zolpidem ER treatment outperformed placebo and 5 mg treatment in 3 of 4 domains on the Cognitive Performance Assessment Battery, and 10 mg. It shows a significant deterioration in 2 out of 4 domains relative to lemborexant. In contrast, neither dose of lemborexant differed from placebo at any time point on cognitive tests.

FIG. 12 shows that treatment with lemborexant (both doses) reduced the length of prolonged wakefulness compared to placebo to a greater extent than treatment with zolpidem ER.

Figure 15 shows that treatment with lemborexant (both doses) significantly increased NREM sleep compared to placebo and treatment with zolpidem ER.

FIG. 16 shows that treatment with lemborexant (both doses) significantly decreased mean REM latencies compared to placebo and treatment with zolpidem ER.

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 each subject's response was analyzed.

subjective sleep onset latency

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

As shown in Table 31, at the start of treatment (first 7 days) and at the end of month 1, responders (defined as those with sWASO ≤60 minutes and a decrease of at least 10 minutes from baseline; , where baseline sWASO was greater than 60 minutes) was statistically significantly superior for treatment with both lemborexant doses compared to treatment with placebo.

Insomnia Severity Index

Table 32 provides a summary and analysis of responders, defined as subjects whose total ISI score decreased by 7 points or more 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 proportions between the lemborexant and placebo groups was statistically significant.

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 47.0% in the 5 mg lemborexant-treated group. 47.8% in the 3% and 10 mg lemborexant treated groups.

As shown in Table 33, at the end of Month 1, the percentage of subjects whose ISI total score had decreased and was less than 10 at Month 1 was 20.3% in the placebo-treated group, 33.0% in the 5 mg lemborexant-treated group and 33.4% in the 10 mg lemborexant-treated group.

Claims (64)

A method of reducing subjective sleep onset latency (sSOL) in a subject comprising administering to said subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein said sSOL is , decreases over at least 1 month relative to baseline. 2. The method of claim 1, wherein the sSOL decreases over baseline for at least 6 months. 2. The method of claim 1, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least one month. 3. The method of claim 2, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least 6 months. 2. The method of claim 1, wherein the sSOL is decreased for at least 20 minutes. 2. The method of claim 1, wherein the sSOL is 40 minutes or less. 7. The method of claim 6, wherein the sSOL is 25 minutes or less. 3. The method of claim 1, wherein the subject has insomnia. A method of improving subjective sleep efficiency (sSE) in a subject comprising administering to said subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, said sSE comprising: Method, wherein relative to baseline increases for at least 1 month. 10. The method of claim 9, wherein the sSE increases over baseline for at least 6 months. 10. The method of claim 9, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least one month. 11. The method of claim 10, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least 6 months. 10. The method of claim 9, wherein the sSE is improved by at least 13%. 10. The method of claim 9, wherein the subject has insomnia. A method of reducing subjective wakefulness (sWASO) in a subject comprising administering to said subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, said sWASO comprising: Method, wherein the decrease over baseline is for at least 1 month. 16. The method of claim 15, wherein the sWASO decreases over baseline for at least 6 months. 16. The method of claim 15, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least one month. 17. The method of claim 16, wherein lemborexant or a pharmaceutically acceptable salt thereof is administered to the subject for at least 6 months. 16. The method of claim 15, wherein the sWASO is decreased for at least 40 minutes. 16. The method of claim 15, wherein the subject has insomnia. A method of identifying a subject responsive to treatment with lemborexant or a pharmaceutically acceptable salt thereof, comprising:
a) determining the subject's pre-treatment period subjective wakefulness (sWASO);
b) if said pre-treatment period sWASO is greater than or equal to 60 minutes, administering 5 mg or 10 mg lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof to said subject over a treatment period;
c) determining sWASO after said treatment period of said subject;
d) if said post-treatment period sWASO is less than 60 minutes and said post-treatment period sWASO is at least 10 minutes less than said pre-treatment period sWASO, said subject is given 5 mg or 10 mg lemborexant or an equivalent dose thereof administering a biologically acceptable salt. 22. The method of claim 21, wherein the post-treatment period sWASO is at least 20 minutes less than the pre-treatment period sWASO. 22. The method of claim 21, wherein the post-treatment period sWASO is at least 30 minutes less than the pre-treatment period sWASO. 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. The method of claim 24, wherein sSE is determined after a treatment period after administration of lemborexant or a pharmaceutically acceptable salt thereof. 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. 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. 22. The method of claim 21, wherein a pretreatment period subjective sleep onset latency (sSOL) is determined prior to administering lemborexant or a pharmaceutically acceptable salt thereof. 29. The method of claim 28, wherein sSOL is determined after a treatment period after administration of lemborexant or a pharmaceutically acceptable salt thereof. 30. The method of claim 29, wherein the post-treatment period sSOL is at least 15 minutes less than the pre-treatment period sSOL. 30. The method of claim 29, wherein the post-treatment period sSOL is at least 20 minutes less than the pre-treatment period sSOL. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said A method, wherein the dosage form is achievable with respect to maintaining a reduction in time to sleep onset in subjective sleep latency (sSOL) compared to placebo during treatment for at least one month. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said A method wherein the dosage form is achievable with respect to maintaining a reduction in time to sleep onset in subjective sleep latency (sSOL) compared to placebo during treatment through 6 months. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said The dosage form can be administered to the patient for at least one month, wherein the dosage form exhibits a reduction in time to sleep onset in subjective sleep onset latency (sSOL) compared to placebo during treatment for at least one month. A method that is achievable with respect to maintaining. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said The dosage form can be administered to a patient for 6 months, and the dosage form maintains a reduction in time to sleep onset in subjective sleep latency (sSOL) compared to placebo during treatment through 6 months. A method that is achievable for doing. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said The method wherein the dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) compared to placebo during treatment for at least one month. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said A method wherein the dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) compared to placebo during treatment through 6 months. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said The dosage form can be administered to the patient for at least one month, wherein said dosage form maintains an improvement in sleep efficiency in subjective sleep efficiency (sSE) compared to placebo during treatment for at least one month. A method that is achievable with respect to A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said The dosage form can be administered to the patient for 6 months, said dosage form being associated with maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) compared to placebo during treatment through 6 months. A method that is achievable. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said The method wherein the dosage form is achievable with respect to maintaining improvement in wakefulness after wakefulness (sWASO) compared to placebo during treatment for at least one month. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said A method wherein the dosage form is achievable with respect to maintaining improvement in wake on wakefulness (sWASO) compared to placebo during treatment through 6 months. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said The dosage form can be administered to the patient for at least one month, and the dosage form is achievable with respect to maintaining improvement in wake on wakefulness (sWASO) compared to placebo during treatment for at least one month. ,Method. A method of treating insomnia comprising orally administering a dosage form comprising lemborexant or a pharmaceutically acceptable salt thereof in a single daily dose in the range of about 5-10 mg, said The dosage form can be administered to a patient for 6 months, and the dosage form is achievable with respect to maintaining improvement in wake on wakefulness (sWASO) compared to placebo during treatment through 6 months. Method. A method of treating insomnia in a subject comprising administering to said subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep onset latency is less than or equal to baseline for at least one month. A method of treating insomnia in a subject comprising administering to said subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep efficiency is less than or equal to baseline for at least one month, the method. A method of treating insomnia in a subject comprising administering to said subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective nocturnal awakening is less than or equal to baseline versus decreasing over at least one month. A method of 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, comprising:
with at least 7 hours remaining until the scheduled wake-up time, orally administering the 5 mg dose of lemborexant or its pharmaceutically acceptable salt to the patient no more than once per night and within several minutes before bedtime. if the 5 mg dose is well tolerated but is not effective, then the dose can be increased to 10 mg once daily;
said dosage form is achievable with respect to maintaining a reduction in time to sleep onset in subjective sleep latency (sSOL) during treatment for at least one month;
The method, wherein said sSOL is decreased by at least 15 minutes relative to baseline. A method of 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, comprising:
with at least 7 hours remaining until the scheduled wake-up time, orally administering the 5 mg dose of lemborexant or its pharmaceutically acceptable salt to the patient no more than once per night and within several minutes before bedtime. if the 5 mg dose is well tolerated but is not effective, then the dose can be increased to 10 mg once daily;
said dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) during treatment for at least one month;
The method, wherein said sSE is improved by at least 4% over baseline. A method of 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, comprising:
with at least 7 hours remaining until the scheduled wake-up time, orally administering the 5 mg dose of lemborexant or its pharmaceutically acceptable salt to the patient no more than once per night and within several minutes before bedtime. if the 5 mg dose is well tolerated but is not effective, then the dose can be increased to 10 mg once daily;
said dosage form is achievable with respect to maintaining improvement in subjective wakefulness after treatment (sWASO) for at least one month;
The method, wherein said sWASO is decreased by at least 29 minutes relative to baseline. A method of 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, comprising:
administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to the patient no more than once per night immediately prior to bedtime with at least 7 hours remaining until the scheduled wake-up time;
The dose may be increased to 10 mg based on clinical response and tolerability;
The method, wherein said dosage form is achievable with respect to maintaining a reduction in time to sleep onset in subjective sleep latency (sSOL) during treatment for at least one month. 51. The method of claim 50, wherein said dosage form is achievable with respect to maintaining a reduction in time to sleep onset in subjective sleep latency (sSOL) during treatment for at least 6 months. 51. The method of claim 50, wherein said dosage form can be administered to said patient for at least one month. 51. The method of claim 50, wherein said dosage form can be administered to said patient for at least 6 months. 51. The method of claim 50, wherein the sSOL is decreased by at least 15 minutes relative to baseline. A method of 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, comprising:
administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof orally to the patient no more than once per night immediately prior to bedtime with at least 7 hours remaining until the scheduled wake-up time;
The dose may be increased to 10 mg based on clinical response and tolerability;
The method, wherein said dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) during treatment for at least one month. 56. The method of claim 55, wherein said dosage form is achievable with respect to maintaining sleep efficiency improvement in subjective sleep efficiency (sSE) during treatment for at least 6 months. 56. The method of claim 55, wherein said dosage form can be administered to said patient for at least one month. 56. The method of claim 55, wherein said dosage form can be administered to said patient for at least 6 months. 56. The method of claim 55, wherein the sSE is improved by at least 4% over baseline. A method of 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, comprising:
orally administering to the patient at least 7 hours before the scheduled wake-up time, the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof no more than once per night immediately prior to bed; Dose may be increased to 10 mg based on clinical response and tolerability,
The method, wherein said dosage form is achievable with respect to maintaining subjective wakefulness (sWASO) improvement during treatment for at least one month. 61. The method of claim 60, wherein said dosage form is achievable with respect to maintaining improvement in subjective wakefulness on sleep (sWASO) during treatment for at least 6 months. 61. The method of claim 60, wherein said dosage form can be administered to said patient for at least one month. 61. The method of claim 60, wherein said dosage form can be administered to said patient for at least 6 months. 61. The method of claim 60, wherein the sWASO is decreased by at least 29 minutes relative to baseline.

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