EP3989976A1 - Lemborexant zur behandlung von schlafstörungen - Google Patents

Lemborexant zur behandlung von schlafstörungen

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Publication number
EP3989976A1
EP3989976A1 EP20832928.4A EP20832928A EP3989976A1 EP 3989976 A1 EP3989976 A1 EP 3989976A1 EP 20832928 A EP20832928 A EP 20832928A EP 3989976 A1 EP3989976 A1 EP 3989976A1
Authority
EP
European Patent Office
Prior art keywords
minutes
relative
reduced
baseline
lemborexant
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP20832928.4A
Other languages
English (en)
French (fr)
Other versions
EP3989976A4 (de
Inventor
Margaret MOLINE
Lynn Kramer
Shobha DHADDA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eisai R&D Management Co Ltd
Original Assignee
Eisai R&D Management Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/US2019/039333 external-priority patent/WO2020263253A1/en
Application filed by Eisai R&D Management Co Ltd filed Critical Eisai R&D Management Co Ltd
Priority claimed from PCT/US2020/039674 external-priority patent/WO2020264201A1/en
Publication of EP3989976A1 publication Critical patent/EP3989976A1/de
Publication of EP3989976A4 publication Critical patent/EP3989976A4/de
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • insomnia sleep disorders such as insomnia are characterized by difficulties with sleep onset, sleep maintenance, or early morning awakening, in association with a complaint of impairment during the daytime.
  • sleep disorders such as insomnia are characterized by difficulties with sleep onset, sleep maintenance, or early morning awakening, in association with a complaint of impairment during the daytime.
  • pharmacological treatments include benzodiazepines, non-benzodiazepine y- aminobutyric acid receptor agonists, suvorexant, a recently approved dual orexin receptor antagonist (DORA), sedating antidepressants, melatonin and melatonin agonists, antihistamines, and other prescription and non-prescription
  • DORA dual orexin receptor antagonist
  • Orexin neuropeptides (orexin-A and orexin-B) have been recognized as critical upstream controllers of most wake-promoting neurotransmitters via 2 G protein-coupled receptors, the orexin-1 receptor and the orexin-2 receptor.
  • Lemborexant also known as E2006, is a dual orexin receptor antagonist. It has been studied in clinical trials and found to possess advantageous properties, for example, reducing wake after sleep onset, sleep onset latency, and/or improving sleep efficiency.
  • a method of reducing subjective sleep onset latency (sSOL) in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a
  • 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
  • sWASO subjective wake after sleep onset
  • a method of identifying a subject responsive to treatment with lemborexant or a pharmaceutically acceptable salt thereof comprising: (a) determining a pre-treatment period subjective wake after sleep onset (sWASO) of the subject; (b) administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is achievable on maintaining reduction a time to sleep onset in Subjective Sleep Onset Latency (sSOL) compared to placebo during the treatment for at least one month.
  • sSOL Subjective Sleep Onset Latency
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is achievable on maintaining reduction a time to sleep onset in Subjective Sleep Onset Latency (sSOL) compared to placebo during the treatment through six months.
  • sSOL Subjective Sleep Onset Latency
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form may be administered to a patient for at least one month, and wherein the dosage form is achievable on maintaining reduction a time to sleep onset in Subjective Sleep Onset Latency (sSOL) compared to placebo during the treatment for at least one month.
  • SOL Subjective Sleep Onset Latency
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form may be administered to a patient for six months, and wherein the dosage form is achievable on maintaining reduction a time to sleep onset in Subjective Sleep Onset Latency (sSOL) compared to placebo during the treatment through six months.
  • SLS Subjective Sleep Onset Latency
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is achievable on maintaining improvement of sleep efficiency in Subjective Sleep Efficiency (sSE) compared to placebo during the treatment for at least one month.
  • sSE Subjective Sleep Efficiency
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is achievable on maintaining improvement of sleep efficiency in Subjective Sleep Efficiency (sSE) compared to placebo during the treatment through six months.
  • sSE Subjective Sleep Efficiency
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form may be administered to a patient for at least one month, and wherein the dosage form is achievable on maintaining improvement of sleep efficiency in Subjective Sleep Efficiency (sSE) compared to placebo during the treatment for at least one month.
  • sSE Subjective Sleep Efficiency
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form may be administered to a patient for six months, and wherein the dosage form is achievable on maintaining improvement of sleep efficiency in Subjective Sleep Efficiency (sSE) compared to placebo during the treatment through six months.
  • sSE Subjective Sleep Efficiency
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is achievable on maintaining improvement of Wake After Sleep Onset (sWASO) compared to placebo during the treatment for at least one month.
  • sWASO Wake After Sleep Onset
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form is achievable on maintaining improvement of Wake After Sleep Onset (sWASO) compared to placebo during the treatment through six months.
  • sWASO Wake After Sleep Onset
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form may be administered to a patient for at least one month, and wherein the dosage form is achievable on maintaining improvement of Wake After Sleep Onset (sWASO) compared to placebo during the treatment for at least one month.
  • sWASO Wake After Sleep Onset
  • a method for treating insomnia comprising administering orally a dosage form comprising
  • lemborexant or a pharmaceutically acceptable salt thereof at a single daily dose ranging from about 5 to 10 mg, wherein the dosage form may be administered to a patient for six months, and wherein the dosage form is achievable on maintaining improvement of Wake After Sleep Onset (sWASO) compared to placebo during the treatment through six months.
  • sWASO Wake After Sleep Onset
  • a method for treating insomnia in a subject comprising administering to the subject 5 mg or 10 mg of
  • lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep onset latency is reduced, relative to baseline, for at least one month.
  • a method for treating insomnia in a subject comprising administering to the subject 5 mg or 10 mg of
  • lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep efficiency is increased, relative to baseline, for at least one month.
  • a method for treating insomnia in a subject comprising administering to the subject 5 mg or 10 mg of
  • lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective wake after sleep onset is reduced, relative to baseline, for at least one month.
  • a method for treating insomnia comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the method comprises orally administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein if the 5 mg dose is well tolerated but not effective, then the dose can be increased to 10 mg once daily, wherein the dosage form is achievable on maintaining reduction a time to sleep onset in subjective Sleep Onset Latency (sSOL) during a treatment for at least one month, and wherein the sSOL is reduced by at least 15 minutes relative to baseline.
  • sSOL subjective Sleep Onset Latency
  • a method for treating insomnia comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the method comprises orally administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night, immediately before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein the daily dose can be increased to 10 mg based on clinical response and tolerability, wherein the dosage form is achievable on maintaining reduction a time to sleep onset in subjective Sleep Onset Latency (sSOL) during a treatment for at least one month, and wherein the sSOL is reduced by at least 15 minutes relative to baseline.
  • sSOL subjective Sleep Onset Latency
  • a method for treating insomnia comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the method comprises orally administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein if the 5 mg dose is well tolerated but not effective, then the dose can be increased to 10 mg once daily, wherein the dosage form is achievable on maintaining improvement of sleep efficiency in subjective Sleep Efficiency (sSE) during a treatment for at least one month, and wherein the sSE is improved by at least 4% relative to baseline.
  • sSE subjective Sleep Efficiency
  • a method for treating insomnia comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the method comprises administering orally the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night, immediately before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein the daily dose may be increased to 10 mg based on clinical response and tolerability, wherein the dosage form is achievable on maintaining improvement of sleep efficiency in subjective Sleep Efficiency (sSE) during a treatment for at least one month, and wherein the sSE is improved by at least 4%, relative to baseline.
  • sSE subjective Sleep Efficiency
  • a method for treating insomnia comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the method comprising orally administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein if the 5 mg dose is well tolerated but not effective, then the dose can be increased to 10 mg once daily, wherein the dosage form is achievable on maintaining improvement of subjective Wake After Sleep Onset (sWASO) during a treatment for at least one month, and wherein the sWASO is reduced by at least 29 minutes relative to baseline.
  • sWASO subjective Wake After Sleep Onset
  • a method for treating insomnia comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the method comprises administering orally the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night, immediately before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein the daily dose may be increased to 10 mg based on clinical response and tolerability, wherein the dosage form is achievable on maintaining improvement of subjective Wake After Sleep Onset (sWASO) during a treatment for at least one month, and wherein the sWASO is reduced by at least 29 minutes relative to baseline.
  • sWASO subjective Wake After Sleep Onset
  • insomnia characterized by difficulties with sleep onset and/or sleep
  • administering comprises administering lemborexant or a
  • FIG. 1 shows the change from baseline in the 1 st and 3 rd quartile median time, as a function of treatment duration, for subjective sleep onset latency in patients treated with placebo, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 2 shows the 1 st and 3 rd quartile median time, as a function of treatment duration, for subjective sleep onset latency in patients treated with placebo, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 3 shows the change from baseline (least squares mean) in sleep efficiency percentage, as a function of treatment duration, for subjective sleep efficiency in patients treated with placebo, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 4 shows the mean sleep efficiency percentage, as a function of treatment duration, for subjective sleep efficiency in patients treated with placebo, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 5 shows the change from baseline (least squares mean) in median time, as a function of treatment duration, for subjective wake after sleep onset in patients treated with placebo, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 6 shows the mean time, as a function of treatment duration, for subjective wake after sleep onset in patients treated with placebo, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 7 shows the change from baseline in the 1 st and 3 rd quartile median time, as a function of treatment duration, for latency to persistent sleep in patients treated with placebo, 6.25 mg of zolpidem, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 8 shows the model estimate for change from baseline, as a function of treatment duration, for sleep efficiency percentage in patients treated with placebo, 6.25 mg of zolpidem, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 9 shows the model estimate for change from baseline, as a function of treatment duration, for wake after sleep onset time in patients treated with placebo, 6.25 mg of zolpidem, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 10 shows the model estimate for change from baseline, as a function of treatment duration, for wake after sleep onset time in the second half of the night in patients treated with placebo, 6.25 mg of zolpidem, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 11 A - FIG. 11 D show the change from baseline (least squares mean) in the four domains of the Cognitive Performance Assessment Battery at Days 2/3 and Days 30/31 in patients treated with placebo, 6.25 mg of zolpidem, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 12 shows the change from baseline (least squares mean) in minutes of duration of long awakenings (defined as a period of wakefulness lasting 5 or more minutes, while trying to sleep) at Days 2/3 and Days 30/31 in patients treated with placebo, 6.25 mg of zolpidem, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 13A, FIG. 13B, and FIG. 13C show the change from baseline (least squares mean) in the minutes asleep during Stage N1 , Stage N2, and Stage N3 sleep, respectively, at Nights 1/2 and Nights 29/30 in patients treated with placebo, 6.25 mg of zolpidem, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 14 shows the change from baseline (least squares mean) in the minutes asleep during non-rapid eye movement (REM) sleep at Nights 1/2 and Nights 29/30 in patients treated with placebo, 6.25 mg of zolpidem, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 15 shows the change from baseline (least squares mean) in the minutes asleep during non-REM sleep at Nights 1/2 and Nights 29/30 in patients treated with placebo, 6.25 mg of zolpidem, 5 mg of lemborexant, or 10 mg of lemborexant.
  • FIG. 16 shows the mean change from baseline in minutes of REM latency at Nights 1/2 and Nights 29/30 in patients treated with placebo, 6.25 mg of zolpidem, 5 mg of lemborexant, or 10 mg of lemborexant.
  • the term“a” refers to one or more.
  • the term“lemborexant” refers to a compound having the structure:
  • the term“therapeutically effective amount” means an amount sufficient to effect an intended result including, but not limited to, a reduction in subjective sleep onset latency, an improvement in subjective sleep efficiency, a reduction in subjective wake after sleep onset, or improvement in insomnia.
  • the present disclosures involve administration to a subject of a therapeutically effective amount of lemborexant or a pharmaceutically
  • 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.
  • 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, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid and the like; and salts formed with organic acids, for example, acetic acid, oxalic acid, tartaric acid, succinic acid, maleic acid, fumaric acid, gluconic acid, citric acid, malic acid, ascorbic acid, benzoic acid, tannic acid, palmitic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, methanesulfonic acid, p- toluenesulfonic acid, naphthalenedisulfonic acid, polygalacturonic acid, and the like; and (b)
  • lemborexant or the pharmaceutically acceptable salt thereof is administered in the form of a composition.
  • the compositions may be in any suitable dosage form.
  • lemborexant or the pharmaceutically acceptable salt thereof is in a solid dosage form, such as, for example, capsules, granules, lozenges, pellets, pills, powders, suspensions, and tablets.
  • the composition further comprises at least one additional pharmaceutically acceptable component.
  • the at least one additional pharmaceutically acceptable component is chosen from pharmaceutically acceptable carriers, pharmaceutically acceptable vehicles, and pharmaceutically acceptable excipients.
  • the term“pharmaceutically acceptable” means that a carrier, diluent, excipient, or vehicle is compatible with other components of a composition and is nontoxic non-toxic to a subject.
  • the term“pharmaceutically acceptable excipient” means an inactive ingredient used as a vehicle (e.g., water, capsule shell, etc.), a diluent, or a component to constitute a dosage form or pharmaceutical composition comprising a drug such as a therapeutic agent.
  • a vehicle e.g., water, capsule shell, etc.
  • a diluent e.g., a component to constitute a dosage form or pharmaceutical composition comprising a drug such as a therapeutic agent.
  • the term also encompasses an inactive ingredient that imparts cohesive function (e.g., binder), disintegrating function (e.g., disintegrator), lubricant function (e.g., lubricating agent), and/or the other function (e.g., solvent, surfactant, etc.) to the
  • the term“subject” means an animal subject, such as a mammalian subject, and for example, a human being. As used herein, the subject may be of any age. In some embodiments, the subject may be 18 years or older. In some embodiments, the subject may be 55 years or older. [0058] As used herein, the terms“treatment” and“treating” refer to an approach for obtaining beneficial or desired results including, but not limited to, therapeutic benefit and/or prophylactic benefit.
  • sSOL subjective sleep onset latency
  • sSOL means the estimated number of minutes from the time that the subject attempted to sleep until sleep onset.
  • sSOL is derived from data entered in a subject’s Sleep Diary.
  • sWASO means the sum of estimated minutes of wake during the night after initial sleep onset until the time the subject stopped trying to sleep for the night, operationalized as the time the subject got out of bed for the day.
  • sWASO is derived from data entered in a subject’s Sleep Diary.
  • an“improvement of sWASO” means a reduction in sWASO.
  • sTST subjective total sleep time
  • sTST means the derived minutes of sleep from sleep onset until the time the subject stopped trying to sleep for the night.
  • sTST is derived from data entered in a subject’s Sleep Diary.
  • sSE subjective sleep efficiency
  • an“improvement of sleep efficiency in Subjective Sleep Efficiency (sSE)” means an increase in sleep efficiency in Subjective Sleep Efficiency (sSE).
  • the sleep parameter is determined by subjective measurements, such as, for example, asking the subject, maintaining a sleep diary, or assessment via a standardized questionnaire regarding how restorative and undisturbed sleep has been (e.g Pittsburgh Sleep Quality Index (Buysse et al., Psychiatry Research (1989), 28(2), 193-213)).
  • sleep diaries were used to assess sleep parameters reported by subjects (i.e. , subjective assessments) including subjective sleep onset latency (sSOL), subjective sleep efficiency (sSE), subjective WASO (sWASO), and subjective total sleep time (sTST). Subjects were instructed to complete the Sleep Diary developed based on the consensus Sleep Diary as described in Carney et al.,“The consensus sleep diary:
  • the Sleep Diary was used to assess the subject’s global perception of quality of sleep on the previous night with the following question: “How would you rate the quality of your sleep last night?” Subjects rated the quality of their sleep on a scale from 1 to 9, with 1 being extremely poor and 9 being extremely good. In some embodiments, the Sleep Diary was used to assess subjective ratings of morning sleepiness with the following question: “How alert/sleepy do you feel this morning?” Subjects rated their
  • ISI Insomnia Severity Index
  • the term“insomnia” means a disorder defined by the Diagnostic and Statistical Manual of Mental Disorders, 5 th Edition (2013;“DSM- V”) having the following diagnostic criteria:
  • a predominant complaint of the subject is dissatisfaction with sleep quantity or quality, associated with one (or more) of the following symptoms:
  • the sleep difficulty occurs at least 3 nights per week.
  • the sleep difficulty is present for at least 3 months.
  • the insomnia is not better explained by and does not occur exclusively during the course of another sleep-wake disorder (e.g., narcolepsy, breathing- related sleep disorder, circadian rhythm sleep-wake disorder, a parasomnia).
  • another sleep-wake disorder e.g., narcolepsy, breathing- related sleep disorder, circadian rhythm sleep-wake disorder, a parasomnia.
  • the insomnia is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication).
  • insomnia also means a sleep disorder characterized by symptoms including, but not limited to, difficulty in falling asleep, difficulty in staying asleep, intermittent wakefulness, and/or waking up too early.
  • the term also encompasses daytime symptoms such as sleepiness, anxiety, impaired concentration, impaired memory, and irritability.
  • Types of insomnia suitable for treatment with lemborexant or a pharmaceutically acceptable salt thereof include short-term insomnia and chronic insomnia.
  • LPS latency to persistent sleep
  • a sleep parameter is determined objectively using polysomnography.
  • Polysomnography is the monitoring of multiple electrophysiological parameters during sleep and generally includes
  • the term“about” means ⁇ 10% of the recited value. For example, if an embodiment is directed to a method where subjective sleep onset latency is reduced by about 10 minutes, then the subjective sleep onset latency is reduced by an amount of time ranging from 9 minutes to 11 minutes.
  • the term“immediately before going to bed” means within five minutes of commencing preparations for sleep or getting into bed.
  • a patient takes lemborexant or a pharmaceutically acceptable salt thereof within five minutes of commencing preparations for sleep.
  • a patient takes lemborexant or a pharmaceutically acceptable salt thereof within two minutes of commencing preparations for sleep.
  • a patient takes lemborexant or a pharmaceutically acceptable salt thereof within five minutes of getting into bed.
  • a patient takes lemborexant or a pharmaceutically acceptable salt thereof within two minutes of getting into bed. In some embodiments, a patient takes lemborexant or a pharmaceutically acceptable salt thereof once in bed.
  • a method of reducing subjective sleep onset latency (sSOL) in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof.
  • lemborexant or a pharmaceutically acceptable salt thereof for use in reducing sSOL in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a
  • the sSOL is reduced for at least one week. In some embodiments, the sSOL is reduced for at least one month. In some embodiments, the sSOL is reduced for at least two months. In some
  • the sSOL is reduced for at least three months.
  • the sSOL is reduced for at least 6 months. In some
  • the sSOL is reduced for at least 9 months.
  • the sSOL is reduced for at least 12 months. In some
  • the sSOL is reduced for at least 18 months.
  • the sSOL is reduced for 2 years or more.
  • the sSOL is reduced for at least one week, relative to baseline. In some embodiments, the sSOL is reduced for at least one month, relative to baseline. In some embodiments, the sSOL is reduced for at least two months, relative to baseline. In some embodiments, the sSOL is reduced for at least three months, relative to baseline. In some embodiments, the sSOL is reduced for at least 6 months, relative to baseline. In some embodiments, the sSOL is reduced for at least 9 months, relative to baseline. In some embodiments, the sSOL is reduced for at least 12 months, relative to baseline. In some embodiments, the sSOL is reduced for at least 18 months, relative to baseline.
  • the sSOL is reduced for 2 years or more, relative to baseline.
  • lemborexant or salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or salt thereof is administered to the subject for at least two months. In some
  • lemborexant or salt thereof is administered to the subject for at least three months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 9 months.
  • lemborexant or salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or salt thereof is administered to the subject for two years or more.
  • the sSOL is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes, relative to baseline.
  • the sSOL is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, 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, relative to baseline.
  • the sSOL is reduced by at least 1 minute, relative to baseline. In some embodiments, the sSOL is reduced by at least 2 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 3 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 4 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 5 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 6 minutes, relative to baseline. In some
  • the sSOL is reduced by at least 7 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 8 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 9 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 9 minutes, relative to baseline.
  • the sSOL is reduced by at least 11 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 12 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 13 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 14 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 15 minutes, relative to baseline. In some embodiments,
  • the sSOL is reduced by at least 16 minutes, relative to baseline.
  • the sSOL is reduced by at least 17 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 18 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 19 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 20 minutes, relative to baseline.
  • the sSOL is reduced by at least 21 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 22 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 23 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 24 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 25 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 26 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 27 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 28 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 29 minutes, relative to baseline.
  • the sSOL is reduced by at least 30 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 31 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 32 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 33 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 34 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 35 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 36 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 37 minutes, relative to baseline.
  • the sSOL is reduced by at least 38 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 39 minutes, relative to baseline. In some embodiments, the sSOL is reduced by at least 40 minutes, relative to baseline.
  • the sSOL is reduced by about 1 minute, relative to baseline. In some embodiments, the sSOL is reduced by about 2 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 3 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 4 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 5 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 6 minutes, relative to baseline. In some
  • the sSOL is reduced by about 7 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 8 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 9 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 9 minutes, relative to baseline.
  • the sSOL is reduced by about 11 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 12 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 13 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 14 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 15 minutes, relative to baseline. In some embodiments,
  • the sSOL is reduced by about 16 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 17 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 18 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 19 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 20 minutes, relative to baseline.
  • the sSOL is reduced by about 21 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 22 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 23 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 24 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 25 minutes, relative to baseline. In some embodiments,
  • the sSOL is reduced by about 26 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 27 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 28 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 29 minutes, relative to baseline.
  • the sSOL is reduced by about 30 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 31 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 32 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 33 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 34 minutes, relative to baseline. In some embodiments,
  • the sSOL is reduced by about 35 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 36 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 37 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 38 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 39 minutes, relative to baseline. In some embodiments, the sSOL is reduced by about 40 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by about 20 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by about 25 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a
  • pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by about 30 minutes.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by at least 20 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by at least 25 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a
  • pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced at least 30 minutes.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by about 25 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by about 30 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by about 35 minutes.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by at least 24 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by about 27 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a
  • pharmaceutically acceptable salt thereof is administered to a subject and the sSOL is reduced by about 32 minutes.
  • sSOL is 1 minute or less, 2 minutes or less, 3 minutes or less, 4 minutes or less, 5 minutes or less, 5 minutes or less, 6 minutes or less, 7 minutes or less, 8 minutes or less, 9 minutes or less, 10 minutes or less, 11 minutes or less, 12 minutes or less, 13 minutes or less, 14 minutes or less, 15 minutes or less, 16 minutes or less, 17 minutes or less, 18 minutes or less, 19 minutes or less, 20 minutes or less, 21 minutes or less, 22 minutes or less, 23 minutes or less, 24 minutes or less, 25 minutes or less, 26 minutes or less, 27 minutes or less, 28 minutes or less, 29 minutes or less, 30 minutes or less, 31 minutes or less, 32 minutes or less, 33 minutes or less, 34 minutes or less, 35 minutes or less, 36 minutes or less, 37 minutes or less, 38 minutes or less, 39 minutes or less, 40 minutes or less, 41 minutes or less, 42 minutes or less, 43 minutes or less, 44 minutes or less, or 45 minutes or less.
  • sSOL is 1 minute or less. In some embodiments, sSOL is 2 minutes or less. In some embodiments, sSOL is 3 minutes or less. In some embodiments, sSOL is 4 minutes or less. In some embodiments, sSOL is 5 minutes or less. In some embodiments, sSOL is 6 minutes or less. In some embodiments, sSOL is 7 minutes or less. In some embodiments, sSOL is 8 minutes or less. In some embodiments, sSOL is 9 minutes or less. In some embodiments, sSOL is 10 minutes or less.
  • sSOL is 11 minutes or less. In some embodiments, sSOL is 12 minutes or less. In some embodiments, sSOL is 13 minutes or less. In some embodiments, sSOL is 14 minutes or less. In some embodiments, sSOL is 15 minutes or less. In some embodiments, sSOL is 16 minutes or less. In some embodiments, sSOL is 17 minutes or less. In some embodiments, sSOL is 18 minutes or less. In some embodiments, sSOL is 19 minutes or less.
  • sSOL is 20 minutes or less. In some embodiments, sSOL is 21 minutes or less. In some embodiments, sSOL is 22 minutes or less. In some embodiments, sSOL is 23 minutes or less. In some embodiments, sSOL is 24 minutes or less. In some embodiments, sSOL is 25 minutes or less. In some embodiments, sSOL is 26 minutes or less. In some embodiments, sSOL is 27 minutes or less. In some embodiments, sSOL is 28 minutes or less. In some embodiments, sSOL is 29 minutes or less.
  • sSOL is 30 minutes or less. In some embodiments, sSOL is 31 minutes or less. In some embodiments, sSOL is 32 minutes or less. In some embodiments, sSOL is 33 minutes or less. In some embodiments, sSOL is 34 minutes or less. In some embodiments, sSOL is 35 minutes or less. In some embodiments, sSOL is 36 minutes or less. In some embodiments, sSOL is 37 minutes or less. In some embodiments, sSOL is 38 minutes or less. In some embodiments, sSOL is 39 minutes or less. [0094] In some embodiments, sSOL is 40 minutes or less. In some embodimentsSOL is 31 minutes or less. In some embodiments, sSOL is 32 minutes or less. In some embodiments, sSOL is 33 minutes or less. In some embodiments, sSOL is 34 minutes or less. In some embodimentsSOL is 35 minutes or less. In some embodiments, sSOL is 36 minutes or less. In some embodiments,
  • sSOL is 41 minutes or less. In some embodiments, sSOL is 42 minutes or less. In some embodiments, sSOL is 43 minutes or less. In some embodiments, sSOL is 44 minutes or less. In some embodiments, sSOL is 45 minutes or less.
  • 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
  • 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, sSOL is about 6 minutes or less. In some embodiments, sSOL is about 7 minutes or less. In some embodiments, sSOL is about 8 minutes or less. In some embodiments, sSOL is about 9 minutes or less. In some embodiments, sSOL is about 10 minutes or less.
  • sSOL is about 11 minutes or less. In some embodiments, sSOL is about 12 minutes or less. In some embodiments, sSOL is about 13 minutes or less. In some embodiments, 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, sSOL is about 17 minutes or less. In some embodiments, sSOL is about 18 minutes or less. In some embodiments, sSOL is about 19 minutes or less.
  • 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, sSOL is about 29 minutes or less.
  • 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, 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, sSOL is about 39 minutes or less.
  • sSOL is about 40 minutes or less. In some embodiments, sSOL is about 41 minutes or less. In some embodiments, sSOL is about 42 minutes or less. In some embodiments, 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.
  • the subject has insomnia.
  • a method of reducing subjective wake after sleep onset (sWASO) in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof.
  • lemborexant or a pharmaceutically acceptable salt thereof for use in reducing sWASO in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a
  • the sWASO is reduced for at least one month. In some embodiments, the sWASO is reduced for at least two months. In some embodiments, the sWASO is reduced for at least three months. In some embodiments, the sWASO is reduced for at least 6 months. In some
  • the sWASO is reduced for at least 9 months.
  • the sWASO is reduced for at least 12 months. In some
  • the sWASO is reduced for at least 18 months.
  • the sWASO is reduced for 2 years or more. [0104] In some embodiments, the sWASO is reduced for at least one month, relative to baseline. In some embodiments, the sWASO is reduced for at least two months, relative to baseline. In some embodiments, the sWASO is reduced for at least three months, relative to baseline. In some embodiments, the sWASO is reduced for at least 6 months, relative to baseline. In some embodiments, the sWASO is reduced for at least 9 months, relative to baseline. In some embodiments, the sWASO is reduced for at least 12 months, relative to baseline. In some embodiments, the sWASO is reduced for at least 18 months, relative to baseline. In some embodiments, the sWASO is reduced for 2 years or more, relative to baseline.
  • lemborexant or salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least three months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 9 months.
  • lemborexant or salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or salt thereof is administered to the subject for two years or more.
  • the sWASO is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes, relative to baseline.
  • the sWASO is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, 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
  • the sWASO is reduced by at least 1 minute, relative to baseline. In some embodiments, the sWASO is reduced by at least 2 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 3 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 4 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 5 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 6 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 7 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 8 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 9 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 9 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 9 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 9 minutes
  • the sWASO is reduced by at least 11 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 12 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 13 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 14 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 15 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 16 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 17 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 18 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 19 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 20 minutes, relative to baseline.
  • the sWASO is reduced by at least 21 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 22 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 23 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 24 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 25 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 26 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 27 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 28 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 29 minutes, relative to baseline.
  • the sWASO is reduced by at least 30 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 31 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 32 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 33 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 34 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 35 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 36 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 37 minutes, relative to baseline.
  • the sWASO is reduced by at least 38 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 39 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 40 minutes, relative to baseline.
  • the sWASO is reduced by at least 41 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 42 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 43 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 44 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 45 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 46 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 47 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 48 minutes, relative to baseline.
  • the sWASO is reduced by at least 49 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 50 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 51 minutes, relative to baseline.
  • the sWASO is reduced by at least 52 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 53 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 54 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 55 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 56 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 57 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 58 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 59 minutes, relative to baseline. In some embodiments, the sWASO is reduced by at least 60 minutes, relative to baseline.
  • the sWASO is reduced by about 1 minute, relative to baseline. In some embodiments, the sWASO is reduced by about 2 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 3 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 4 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 5 minutes, relative to baseline. In some
  • the sWASO is reduced by about 6 minutes, relative to baseline.
  • the sWASO is reduced by about 7 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 8 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 9 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 9 minutes, relative to baseline.
  • the sWASO is reduced by about 11 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 12 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 13 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 14 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 15 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 16 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 17 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 18 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 19 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 20 minutes, relative to baseline.
  • the sWASO is reduced by about 21 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 22 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 23 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 24 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 25 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 26 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 27 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 28 minutes, relative to baseline.
  • the sWASO is reduced by about 29 minutes, relative to baseline. [0116] In some embodiments, the sWASO is reduced by about 30 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 31 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 32 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 33 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 34 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 35 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 36 minutes, relative to baseline.
  • the sWASO is reduced by about 37 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 38 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 39 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 40 minutes, relative to baseline.
  • the sWASO is reduced by about 41 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 42 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 43 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 44 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 45 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 46 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 47 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 48 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 49 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 50 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 51 minutes, relative to baseline.
  • the sWASO is reduced by about 52 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 53 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 54 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 55 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 56 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 57 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 58 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 59 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 60 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced 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 a subject and the sWASO is reduced 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 a subject and the sWASO is reduced by about 45 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by about 55 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by at least 20 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by at least 23 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by at least 42 minutes, relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by at least 51 minutes, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by about 25 minutes, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced 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 a subject and the sWASO is reduced 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 a subject and the sWASO is reduced by about 50 minutes, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by at least 23 minutes, relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject 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 a subject and the sWASO is reduced by at least 39 minutes, relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by at least 48 minutes, relative to baseline.
  • the sWASO is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes, relative to placebo.
  • the sWASO is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, 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, relative to placebo.
  • the sWASO is reduced by at least 1 minute, relative to placebo. In some embodiments, the sWASO is reduced by at least 2 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 3 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 4 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 5 minutes, relative to placebo. In some embodiments,
  • the sWASO is reduced by at least 6 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 7 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 8 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 9 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 10 minutes, relative to placebo.
  • the sWASO is reduced by at least 11 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 12 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 13 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 14 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 15 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 16 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 17 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 18 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 19 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 20 minutes, relative to placebo.
  • the sWASO is reduced by at least 21 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 22 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 23 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 24 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 25 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 26 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 27 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 28 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 29 minutes, relative to placebo. In some embodiments, the sWASO is reduced by at least 30 minutes, relative to placebo.
  • the sWASO is reduced by about 1 minute, relative to placebo. In some embodiments, the sWASO is reduced by about 2 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 3 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 4 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 5 minutes, relative to placebo. In some embodiments,
  • the sWASO is reduced by about 6 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 7 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 8 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 9 minutes, relative to baseline. In some embodiments, the sWASO is reduced by about 10 minutes, relative to placebo.
  • the sWASO is reduced by about 11 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 12 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 13 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 14 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 15 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 16 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 17 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 18 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 19 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 20 minutes, relative to placebo.
  • the sWASO is reduced by about 21 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 22 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 23 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 24 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 25 minutes, relative to placebo. In some embodiments,
  • the sWASO is reduced by about 26 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 27 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 28 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 29 minutes, relative to placebo. In some embodiments, the sWASO is reduced by about 30 minutes, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by about 5 minutes, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a 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 a subject and the sWASO is reduced by about 20 minutes, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by at least 5 minutes, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a 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 a subject and the sWASO is reduced by at least 14 minutes, relative to placebo. In some embodiments, 5 mg of lemborexant or an
  • a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by at least 17 minutes, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sWASO is reduced by about 5 minutes, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a 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 a subject and the sWASO is reduced by about 15 minutes, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a 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 a 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 a 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 a subject and the sWASO is reduced by at least 16 minutes, relative to placebo.
  • the subject has insomnia.
  • 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.
  • lemborexant or a pharmaceutically acceptable salt thereof for use in improving sSE in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a
  • the sSE is improved for at least one month. In some embodiments, the sSE is improved for at least two months. In some embodiments, the sSE is improved for at least three months. In some
  • the sSE is improved for at least 6 months. In some embodiments, the sSE is improved for at least 9 months. In some embodiments, the sSE is improved for at least 12 months. In some embodiments, the sSE is improved for at least 18 months. In some embodiments, the sSE is improved for 2 years or more. [0137] In some embodiments, the sSE is improved for at least one month, relative to baseline. In some embodiments, the sSE is improved for at least two months, relative to baseline. In some embodiments, the sSE is improved for at least three months, relative to baseline. In some embodiments, the sSE is improved for at least 6 months, relative to baseline. In some embodiments, the sSE is improved for at least 9 months, relative to baseline. In some
  • the sSE is improved for at least 12 months, relative to baseline.
  • the sSE is improved for at least 18 months, relative to baseline. In some embodiments, the sSE is improved for 2 years or more, relative to baseline.
  • lemborexant or salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least three months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 9 months.
  • lemborexant or salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or salt thereof is administered to the subject for two years or more.
  • the sSE is improved by at least 1 %, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, or at least 50%, relative to baseline. In some embodiments, the sSE is improved by at least 1 %, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 1 1 %, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21 %, at least 22%, at least 23%, at least 24%, or at least 25%, relative to baseline.
  • the sSE is improved by at least 1 %, relative to baseline. In some embodiments, the sSE is improved by at least 2%, relative to baseline. In some embodiments, the sSE is improved by at least 3%, relative to baseline. In some embodiments, the sSE is improved by at least 4%, relative to baseline. In some embodiments, the sSE is improved by at least 5%, relative to baseline. In some embodiments, the sSE is improved by at least 6%, relative to baseline. In some embodiments, the sSE is improved by at least 7%, relative to baseline. In some embodiments, the sSE is improved by at least 8%, relative to baseline. In some embodiments, the sSE is improved by at least 9%, relative to baseline.
  • the sSE is improved by at least 10%, relative to baseline. In some embodiments, the sSE is improved by at least 1 1 %, relative to baseline. In some embodiments, the sSE is improved by at least 12%, relative to baseline. In some embodiments, the sSE is improved by at least 13%, relative to baseline. In some embodiments, the sSE is improved by at least 14%, relative to baseline. In some embodiments, the sSE is improved by at least 15%, relative to baseline. In some embodiments, the sSE is improved by at least 16%, relative to baseline. In some embodiments, the sSE is improved by at least 17%, relative to baseline.
  • the sSE is improved by at least 18%, relative to baseline. In some embodiments, the sSE is improved by at least 19%, relative to baseline. [0142] In some embodiments, the sSE is improved by at least 20%, relative to baseline. In some embodiments, the sSE is improved by at least 21 %, relative to baseline. In some embodiments, the sSE is improved by at least 22%, relative to baseline. In some embodiments, the sSE is improved by at least 23%, relative to baseline. In some embodiments, the sSE is improved by at least 24%, relative to baseline. In some embodiments, the sSE is improved by at least 25%, relative to baseline.
  • the sSE is improved by about 1 %, relative to baseline. In some embodiments, the sSE is improved by about 2%, relative to baseline. In some embodiments, the sSE is improved by about 3%, relative to baseline. In some embodiments, the sSE is improved by about 4%, relative to baseline. In some embodiments, the sSE is improved by about 5%, relative to baseline. In some embodiments, the sSE is improved by about 6%, relative to baseline. In some embodiments, the sSE is improved by about 7%, relative to baseline. In some embodiments, the sSE is improved by about 8%, relative to baseline. In some embodiments, the sSE is improved by about 9%, relative to baseline.
  • the sSE is improved by about 10%, relative to baseline. In some embodiments, the sSE is improved by about 11 %, relative to baseline. In some embodiments, the sSE is improved by about 12%, relative to baseline. In some embodiments, the sSE is improved by about 13%, relative to baseline. In some embodiments, the sSE is improved by about 14%, relative to baseline. In some embodiments, the sSE is improved by about 15%, relative to baseline. In some embodiments, the sSE is improved by about 16%, relative to baseline. In some embodiments, the sSE is improved by about 17%, relative to baseline. In some embodiments, the sSE is improved by about 18%, relative to baseline. In some embodiments, the sSE is improved by about 19%, relative to baseline.
  • the sSE is improved by about 20%, relative to baseline. In some embodiments, the sSE is improved by about 21 %, relative to baseline. In some embodiments, the sSE is improved by about 22%, relative to baseline. In some embodiments, the sSE is improved by about 23%, relative to baseline. In some embodiments, the sSE is improved by about 24%, relative to baseline. In some embodiments, the sSE is improved by about 25%, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 6%, relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 7%, relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 13%, relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 15%, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by about 6%, relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by about 7%, relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by about 13%, relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by about 15%, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 8%, relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 9%, relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 13%, relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 15%, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by about 8%, relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by about 9%, relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by about 13%, relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by about 15%, relative to baseline.
  • the sSE is improved by at least 1 %, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, or at least 50%, relative to placebo. In some embodiments, the sSE is improved by at least 1 %, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, or at least 10%, relative to placebo.
  • the sSE is improved by at least 1 %, relative to placebo. In some embodiments, the sSE is improved by at least 2%, relative to placebo. In some embodiments, the sSE is improved by at least 3%, relative to placebo. In some embodiments, the sSE is improved by at least 4%, relative to placebo. In some embodiments, the sSE is improved by at least 5%, relative to placebo.
  • the sSE is improved by at least 6%, relative to placebo. In some embodiments, the sSE is improved by at least 7%, relative to placebo. In some embodiments, the sSE is improved by at least 8%, relative to placebo. In some embodiments, the sSE is improved by at least 9%, relative to placebo. In some embodiments, the sSE is improved by at least 10%, relative to placebo.
  • the sSE is improved by about 1 %, relative to placebo. In some embodiments, the sSE is improved by about 2%, relative to placebo. In some embodiments, the sSE is improved by about 3%, relative to placebo. In some embodiments, the sSE is improved by about 4%, relative to placebo. In some embodiments, the sSE is improved by about 5%, relative to placebo.
  • the sSE is improved by about 6%, relative to placebo. In some embodiments, the sSE is improved by about 7%, relative to placebo. In some embodiments, the sSE is improved by about 8%, relative to placebo. In some embodiments, the sSE is improved by about 9%, relative to placebo. In some embodiments, the sSE is improved by about 10%, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 2%, relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 4%, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 2%, relative to baseline. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 4%, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 3%, 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 the sSE is improved by at least 4%, 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 the sSE is improved by at least 5%, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the sSE is improved by at least 3%, 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 the sSE is improved by at least 4%, 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 the sSE is improved by at least 5%, relative to placebo.
  • LPS persistent sleep
  • lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is also disclosed herein.
  • lemborexant or a pharmaceutically acceptable salt thereof for use in reducing LPS in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a
  • the LPS is reduced for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days. In some embodiments, the LPS is reduced for at least 1 day.
  • the LPS is reduced for at least 2 days. In some embodiments, the LPS is reduced for at least 3 days. In some embodiments, the LPS is reduced for at least 4 days. In some embodiments, the LPS is reduced for at least 5 days. In some embodiments, the LPS is reduced for at least 6 days. In some embodiments, the LPS is reduced for at least 7 days. In some embodiments, the LPS is reduced for at least 8 days. In some embodiments, the LPS is reduced for at least 9 days. In some embodiments, the LPS is reduced for at least 10 days.
  • the LPS is reduced for at least 11 days. In some embodiments, the LPS is reduced for at least 12 days. In some embodiments, the LPS is reduced for at least 13 days. In some embodiments, the LPS is reduced for at least 14 days. In some embodiments, the LPS is reduced for at least 15 days. In some embodiments, the LPS is reduced for at least 16 days.
  • the LPS is reduced for at least 17 days. In some embodiments, the LPS is reduced for at least 18 days. In some embodiments, the LPS is reduced for at least 19 days.
  • the LPS is reduced for at least 20 days. In some embodiments, the LPS is reduced for at least 21 days. In some embodiments, the LPS is reduced for at least 22 days. In some embodiments, the LPS is reduced for at least 23 days. In some embodiments, the LPS is reduced for at least 24 days. In some embodiments, the LPS is reduced for at least 25 days.
  • the LPS is reduced for at least 26 days. In some embodiments, the LPS is reduced for at least 27 days. In some embodiments, the LPS is reduced for at least 28 days. In some embodiments, the LPS is reduced for at least 29 days. In some embodiments, the LPS is reduced for at least 30 days.
  • the LPS is reduced for at least one month. In some embodiments, the LPS is reduced for at least two months. In some embodiments, the LPS is reduced for at least three months. In some
  • the LPS is reduced for at least 6 months. In some embodiments, the LPS is reduced for at least 9 months. In some embodiments, the LPS is reduced for at least 12 months. In some embodiments, the LPS is reduced for at least 18 months. In some embodiments, the LPS is reduced for 2 years or more.
  • the LPS is reduced for at least one month. In some embodiments, the LPS is reduced for at least two months, relative to baseline. In some embodiments, the LPS is reduced for at least three months, relative to baseline. In some embodiments, the LPS is reduced for at least 6 months, relative to baseline. In some embodiments, the LPS is reduced for at least 9 months, relative to baseline. In some embodiments, the LPS is reduced for at least 12 months, relative to baseline. In some embodiments, the LPS is reduced for at least 18 months, relative to baseline. In some embodiments, the LPS is reduced for 2 years or more, relative to baseline.
  • lemborexant or salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or salt thereof is administered to the subject for at least two months. In some
  • lemborexant or salt thereof is administered to the subject for at least three months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 9 months.
  • lemborexant or salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or salt thereof is administered to the subject for two years or more.
  • the LPS is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes, relative to baseline.
  • the LPS is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, 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, relative to baseline.
  • the LPS is reduced by at least 1 minute, relative to baseline. In some embodiments, the LPS is reduced by at least 2 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 3 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 4 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 5 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 6 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 7 minutes, relative to baseline. In some
  • the LPS is reduced by at least 8 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 9 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 10 minutes, relative to baseline.
  • the LPS is reduced by at least 11 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 12 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 13 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 14 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 15 minutes, relative to baseline. In some embodiments,
  • the LPS is reduced by at least 16 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 17 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 18 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 19 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 20 minutes, relative to baseline.
  • the LPS is reduced by at least 21 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 22 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 23 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 24 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 25 minutes, relative to baseline. In some embodiments,
  • the LPS is reduced by at least 26 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 27 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 28 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 29 minutes, relative to baseline.
  • the LPS is reduced by at least 30 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 31 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 32 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 33 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 34 minutes, relative to baseline. In some embodiments,
  • the LPS is reduced by at least 35 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 36 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 37 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 38 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 39 minutes, relative to baseline. In some embodiments, the LPS is reduced by at least 40 minutes, relative to baseline.
  • the LPS is reduced by about 1 minute, relative to baseline. In some embodiments, the LPS is reduced by about 2 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 3 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 4 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 5 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 6 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 7 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 8 minutes, relative to baseline. In some
  • the LPS is reduced by about 9 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 10 minutes, relative to baseline.
  • the LPS is reduced by about 11 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 12 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 13 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 14 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 15 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 16 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 11 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 12 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 13 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 14 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 15 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 16 minutes, relative to baseline. In some
  • the LPS is reduced by about 17 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 18 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 19 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 20 minutes, relative to baseline.
  • the LPS is reduced by about 21 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 22 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 23 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 24 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 25 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 26 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 27 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 28 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 29 minutes, relative to baseline.
  • the LPS is reduced by about 30 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 31 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 32 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 33 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 34 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 35 minutes, relative to baseline. In some embodiments,
  • the LPS is reduced by about 36 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 37 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 38 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 39 minutes, relative to baseline. In some embodiments, the LPS is reduced by about 40 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a 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 a subject and the LPS is reduced by about 19 minutes.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the LPS is reduced by at least 16 minutes. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the LPS is reduced by at least 19 minutes.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the LPS is reduced by about 19 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the LPS is reduced by about 21 minutes.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the LPS is reduced by at least 19 minutes. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the LPS is reduced by at least 21 minutes.
  • LPS is 1 minute or less, 2 minutes or less, 3 minutes or less, 4 minutes or less, 5 minutes or less, 5 minutes or less, 6 minutes or less, 7 minutes or less, 8 minutes or less, 9 minutes or less, 10 minutes or less, 11 minutes or less, 12 minutes or less, 13 minutes or less, 14 minutes or less, 15 minutes or less, 16 minutes or less, 17 minutes or less, 18 minutes or less, 19 minutes or less, 20 minutes or less, 21 minutes or less, 22 minutes or less, 23 minutes or less, 24 minutes or less, 25 minutes or less, 26 minutes or less, 27 minutes or less, 28 minutes or less, 29 minutes or less, 30 minutes or less, 31 minutes or less, 32 minutes or less, 33 minutes or less, 34 minutes or less, 35 minutes or less, 36 minutes or less, 37 minutes or less, 38 minutes or less, 39 minutes or less, 40 minutes or less, 41 minutes or less, 42 minutes or less, 43 minutes or less, 44 minutes or less, or 45 minutes or less.
  • LPS is 1 minute or less. In some embodiments, LPS is 2 minutes or less. In some embodiments, LPS is 3 minutes or less. In some embodiments, LPS is 4 minutes or less. In some embodiments, LPS is 5 minutes or less. In some embodiments, LPS is 6 minutes or less. In some embodiments, LPS is 7 minutes or less. In some embodiments, LPS is 8 minutes or less. In some embodiments, LPS is 9 minutes or less. In some embodiments, LPS is 10 minutes or less.
  • LPS is 11 minutes or less. In some embodiments,
  • LPS is 12 minutes or less. In some embodiments, LPS is 13 minutes or less. In some embodiments, LPS is 14 minutes or less. In some embodiments, LPS is 15 minutes or less. In some embodiments, LPS is 16 minutes or less. In some embodiments, LPS is 17 minutes or less. In some embodiments, LPS is 18 minutes or less. In some embodiments, LPS is 19 minutes or less.
  • LPS is 20 minutes or less. In some embodiments,
  • LPS is 21 minutes or less. In some embodiments, LPS is 22 minutes or less. In some embodiments, LPS is 23 minutes or less. In some embodiments, LPS is 24 minutes or less. In some embodiments, LPS is 25 minutes or less. In some embodiments, LPS is 26 minutes or less. In some embodiments, LPS is 27 minutes or less. In some embodiments, LPS is 28 minutes or less. In some embodiments, LPS is 29 minutes or less.
  • LPS is 30 minutes or less. In some embodiments,
  • LPS is 31 minutes or less. In some embodiments, LPS is 32 minutes or less. In some embodiments, LPS is 33 minutes or less. In some embodiments, LPS is 34 minutes or less. In some embodiments, LPS is 35 minutes or less. In some embodiments, LPS is 36 minutes or less. In some embodiments, LPS is 37 minutes or less. In some embodiments, LPS is 38 minutes or less. In some embodiments, LPS is 39 minutes or less.
  • LPS is 40 minutes or less. In some embodiments,
  • LPS is 41 minutes or less. In some embodiments, LPS is 42 minutes or less. In some embodiments, LPS is 43 minutes or less. In some embodiments, LPS is 44 minutes or less. In some embodiments, LPS is 45 minutes or less.
  • 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
  • LPS is about 1 minute or less. In some embodiments, LPS is about 2 minutes or less. In some embodiments, LPS is about 3 minutes or less. In some embodiments, LPS is about 4 minutes or less. In some embodiments, LPS is about 5 minutes or less. In some embodiments, LPS is about 6 minutes or less. In some embodiments, LPS is about 7 minutes or less. In some embodiments, LPS is about 8 minutes or less. In some embodiments, LPS is about 9 minutes or less. In some embodiments, LPS is about 10 minutes or less.
  • LPS is about 11 minutes or less. In some embodiments, LPS is about 12 minutes or less. In some embodiments, LPS is about 13 minutes or less. In some embodiments, LPS is about 14 minutes or less. In some embodiments, LPS is about 15 minutes or less. In some embodiments, LPS is about 16 minutes or less. In some embodiments, LPS is about 17 minutes or less. In some embodiments, LPS is about 18 minutes or less. In some embodiments, LPS is about 19 minutes or less.
  • LPS is about 20 minutes or less. In some embodiments, LPS is about 21 minutes or less. In some embodiments, LPS is about 22 minutes or less. In some embodiments, LPS is about 23 minutes or less. In some embodiments, LPS is about 24 minutes or less. In some embodiments, LPS is about 25 minutes or less. In some embodiments, LPS is about 26 minutes or less. In some embodiments, LPS is about 27 minutes or less. In some embodiments, LPS is about 28 minutes or less. In some embodiments, LPS is about 29 minutes or less.
  • LPS is about 30 minutes or less. In some embodiments, LPS is about 31 minutes or less. In some embodiments, LPS is about 32 minutes or less. In some embodiments, LPS is about 33 minutes or less. In some embodiments, LPS is about 34 minutes or less. In some embodiments, LPS is about 35 minutes or less. In some embodiments, LPS is about 36 minutes or less. In some embodiments, LPS is about 37 minutes or less. In some embodiments, LPS is about 38 minutes or less. In some embodiments, LPS is about 39 minutes or less.
  • LPS is about 40 minutes or less. In some embodiments, LPS is about 41 minutes or less. In some embodiments, LPS is about 42 minutes or less. In some embodiments, LPS is about 43 minutes or less. In some embodiments, LPS is about 44 minutes or less. In some embodiments, LPS is about 45 minutes or less.
  • the subject has insomnia.
  • a method of reducing wake after sleep onset (WASO) in a subject comprising administering to the subject 5 mg or 10 mg of
  • lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is also disclosed herein.
  • lemborexant or a pharmaceutically acceptable salt thereof for use in reducing WASO in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a
  • the WASO is reduced for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days. In some embodiments, the WASO is reduced for at least 1 day.
  • the WASO is reduced for at least 2 days. In some embodiments, the WASO is reduced for at least 3 days. In some embodiments, the WASO is reduced for at least 4 days. In some embodiments, the WASO is reduced for at least 5 days. In some embodiments, the WASO is reduced for at least 6 days. In some embodiments, the WASO is reduced for at least 7 days. In some embodiments, the WASO is reduced for at least 8 days. In some embodiments, the WASO is reduced for at least 9 days. In some embodiments, the WASO is reduced for at least 10 days.
  • the WASO is reduced for at least 11 days. In some embodiments, the WASO is reduced for at least 12 days. In some embodiments, the WASO is reduced for at least 13 days. In some
  • the WASO is reduced for at least 14 days. In some embodiments, the WASO is reduced for at least 14 days. In some embodiments, the WASO is reduced for at least 14 days.
  • the WASO is reduced for at least 15 days. In some embodiments, the WASO is reduced for at least 15 days.
  • the WASO is reduced for at least 16 days. In some embodiments, the WASO is reduced for at least 16 days.
  • the WASO is reduced for at least 17 days. In some embodiments, the WASO is reduced for at least 17 days. In some embodiments, the WASO is reduced for at least 17 days.
  • the WASO is reduced for at least 18 days. In some embodiments, the WASO is reduced for at least 18 days.
  • the WASO is reduced for at least 19 days.
  • the WASO is reduced for at least 20 days. In some embodiments, the WASO is reduced for at least 21 days. In some embodiments, the WASO is reduced for at least 22 days. In some
  • the WASO is reduced for at least 23 days. In some embodiments, the WASO is reduced for at least 23 days. In some embodiments, the WASO is reduced for at least 23 days.
  • the WASO is reduced for at least 24 days. In some embodiments, the WASO is reduced for at least 25 days. In some embodiments, the WASO is reduced for at least 26 days. In some
  • the WASO is reduced for at least 27 days. In some embodiments, the WASO is reduced for at least 27 days.
  • the WASO is reduced for at least 28 days. In some embodiments, the WASO is reduced for at least 28 days.
  • the WASO is reduced for at least 29 days. In some embodiments, the WASO is reduced for at least 29 days.
  • the WASO is reduced for at least 30 days.
  • the WASO is reduced for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days, relative to baseline.
  • the WASO is reduced for at least 1 day, relative to baseline.
  • the WASO is reduced for at least 2 days, relative to baseline.
  • the WASO is reduced for at least 3 days, relative to baseline.
  • the WASO is reduced for at least 4 days, relative to baseline.
  • the WASO is reduced for at least 5 days, relative to baseline. In some embodiments, the WASO is reduced for at least 6 days, relative to baseline. In some embodiments, the WASO is reduced for at least 7 days, relative to baseline. In some embodiments, the WASO is reduced for at least 8 days, relative to baseline. In some embodiments, the WASO is reduced for at least 9 days, relative to baseline. In some embodiments, the WASO is reduced for at least 10 days, relative to baseline. [0197] In some embodiments, the WASO is reduced for at least 11 days, relative to baseline. In some embodiments, the WASO is reduced for at least 12 days, relative to baseline. In some embodiments, the WASO is reduced for at least 13 days, relative to baseline. In some embodiments, the WASO is reduced for at least 14 days, relative to baseline. In some embodiments, the WASO is reduced for at least 15 days, relative to baseline. In some embodiments, the WASO is reduced for at least 16 days, relative to baseline. In some embodiments, the WASO is reduced for at least 11 days
  • the WASO is reduced for at least 17 days, relative to baseline. In some embodiments, the WASO is reduced for at least 18 days, relative to baseline. In some embodiments, the WASO is reduced for at least 19 days, relative to baseline.
  • the WASO is reduced for at least 20 days, relative to baseline. In some embodiments, the WASO is reduced for at least 21 days, relative to baseline. In some embodiments, the WASO is reduced for at least 22 days, relative to baseline. In some embodiments, the WASO is reduced for at least 23 days, relative to baseline. In some embodiments, the WASO is reduced for at least 24 days, relative to baseline. In some embodiments, the WASO is reduced for at least 25 days, relative to baseline. In some
  • the WASO is reduced for at least 26 days, relative to baseline. In some embodiments, the WASO is reduced for at least 27 days, relative to baseline. In some embodiments, the WASO is reduced for at least 28 days, relative to baseline. In some embodiments, the WASO is reduced for at least 29 days, relative to baseline. In some embodiments, the WASO is reduced for at least 30 days, relative to baseline. [0199] In some embodiments, the WASO is reduced for at least one month. In some embodiments, the WASO is reduced for at least two months. In some embodiments, the WASO is reduced for at least three months. In some embodiments, the WASO is reduced for at least 6 months. In some embodiments,
  • the WASO is reduced for at least 9 months. In some embodiments, the WASO is reduced for at least 9 months. In some embodiments, the WASO is reduced for at least 9 months.
  • the WASO is reduced for at least 12 months. In some embodiments, the WASO is reduced for at least 12 months. In some embodiments, the WASO is reduced for at least 12 months.
  • the WASO is reduced for at least 18 months. In some embodiments, the WASO is reduced for at least 18 months. In some embodiments, the WASO is reduced for at least 18 months.
  • the WASO is reduced for 2 years or more.
  • the WASO is reduced for at least one month, relative to baseline. In some embodiments, the WASO is reduced for at least two months, relative to baseline. In some embodiments, the WASO is reduced for at least three months, relative to baseline. In some embodiments, the WASO is reduced for at least 6 months, relative to baseline. In some embodiments, the WASO is reduced for at least 9 months, relative to baseline. In some
  • the WASO is reduced for at least 12 months, relative to baseline. In some embodiments, the WASO is reduced for at least 18 months, relative to baseline. In some embodiments, the WASO is reduced for 2 years or more, relative to baseline.
  • lemborexant or salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least three months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 9 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or salt thereof is administered to the subject for two years or more.
  • the WASO is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes, relative to baseline.
  • the WASO is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, 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
  • the WASO is reduced by at least 1 minute, relative to baseline. In some embodiments, the WASO is reduced by at least 2 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 3 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 4 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 5 minutes, relative to baseline. In some embodiments,
  • the WASO is reduced by at least 6 minutes, relative to baseline.
  • the WASO is reduced by at least 7 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 8 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 9 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 10 minutes, relative to baseline.
  • the WASO is reduced by at least 11 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 12 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 13 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 14 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 15 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 16 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 17 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 18 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 19 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 20 minutes, relative to baseline.
  • the WASO is reduced by at least 21 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 22 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 23 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 24 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 25 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 26 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 27 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 28 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 29 minutes, relative to baseline.
  • the WASO is reduced by at least 30 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 31 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 32 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 33 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 34 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 35 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 36 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 37 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 38 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 39 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 40 minutes, relative to baseline.
  • the WASO is reduced by at least 41 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 42 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 43 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 44 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 45 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 46 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 47 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 48 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 49 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 50 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 51 minutes, relative to baseline.
  • the WASO is reduced by at least 52 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 53 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 54 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 55 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 56 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 57 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 58 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 59 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 60 minutes, relative to baseline.
  • the WASO is reduced by at least 61 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 62 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 63 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 64 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 65 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 66 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 67 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 68 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 69 minutes, relative to baseline. In some embodiments, the WASO is reduced by at least 70 minutes, relative to baseline.
  • the WASO is reduced by about 1 minute, relative to baseline. In some embodiments, the WASO is reduced by about 2 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 3 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 4 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 5 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 6 minutes, relative to baseline. In some
  • the WASO is reduced by about 7 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 8 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 9 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 10 minutes, relative to baseline.
  • the WASO is reduced by about 11 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 12 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 13 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 14 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 15 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 16 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 17 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 18 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 19 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 20 minutes, relative to baseline.
  • the WASO is reduced by about 21 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 22 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 23 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 24 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 25 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 26 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 27 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 28 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 29 minutes, relative to baseline.
  • the WASO is reduced by about 30 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 31 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 32 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 33 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 34 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 35 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 36 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 37 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 38 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 39 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 40 minutes, relative to baseline.
  • the WASO is reduced by about 41 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 42 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 43 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 44 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 45 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 46 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 47 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 48 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 49 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 50 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 51 minutes, relative to baseline.
  • the WASO is reduced by about 52 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 53 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 54 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 55 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 56 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 57 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 58 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 59 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 60 minutes, relative to baseline.
  • the WASO is reduced by about 61 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 62 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 63 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 64 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 65 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 66 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 67 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 68 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 69 minutes, relative to baseline.
  • the WASO is reduced by about 70 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 44 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 50 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by 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 a subject and the WASO is reduced by at least 49 minutes, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 46 minutes, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 60 minutes, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by at least 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 a subject and the sWASO is reduced by at least 59 minutes, relative to baseline. [0221 ] In some embodiments, the WASO is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes, relative to placebo.
  • the WASO is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, at least 26 minutes, at least 27 minutes, at least 28 minutes, at least 29 minutes, at least 30 minutes, at least 31 minutes, at least 32 minutes, at least 33 minutes, at least 34 minutes, or at least
  • the WASO is reduced by at least 1 minute, relative to placebo. In some embodiments, the WASO is reduced by at least 2 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 3 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 4 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 5 minutes, relative to placebo. In some embodiments,
  • the WASO is reduced by at least 6 minutes, relative to placebo.
  • the WASO is reduced by at least 7 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 8 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 9 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 10 minutes, relative to placebo.
  • the WASO is reduced by at least 11 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 12 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 13 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 14 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 15 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 16 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 17 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 18 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 19 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 20 minutes, relative to placebo.
  • the WASO is reduced by at least 21 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 22 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 23 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 24 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 25 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 26 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 27 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 28 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 29 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 30 minutes, relative to placebo.
  • the WASO is reduced by at least 31 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 32 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 33 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 34 minutes, relative to placebo. In some embodiments, the WASO is reduced by at least 35 minutes, relative to placebo.
  • the WASO is reduced by about 1 minute, relative to placebo. In some embodiments, the WASO is reduced by about 2 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 3 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 4 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 5 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 6 minutes, relative to placebo. In some
  • the WASO is reduced by about 7 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 8 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 9 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 10 minutes, relative to placebo.
  • the WASO is reduced by about 11 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 12 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 13 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 14 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 15 minutes, relative to placebo. In some embodiments,
  • the WASO is reduced by about 16 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 17 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 18 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 19 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 20 minutes, relative to placebo.
  • the WASO is reduced by about 21 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 22 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 23 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 24 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 25 minutes, relative to placebo. In some embodiments,
  • the WASO is reduced by about 26 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 27 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 28 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 29 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 30 minutes, relative to placebo.
  • the WASO is reduced by about 31 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 32 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 33 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 34 minutes, relative to placebo. In some embodiments, the WASO is reduced by about 35 minutes, relative to placebo. [0230] In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 25 minutes, relative to placebo. In some
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 35 minutes, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by at least 23 minutes, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by at least 33 minutes, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 25 minutes, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 40 minutes, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by at least 25 minutes, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by at least 42 minutes, relative to placebo.
  • the WASO is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes, relative to zolpidem.
  • the WASO is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, relative to zolpidem.
  • the WASO is reduced by at least 1 minute, relative to zolpidem. In some embodiments, the WASO is reduced by at least 2 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 3 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 4 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 5 minutes, relative to zolpidem. In some
  • the WASO is reduced by at least 6 minutes, relative to zolpidem.
  • the WASO is reduced by at least 7 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 8 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 9 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 10 minutes, relative to zolpidem.
  • the WASO is reduced by at least 11 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 12 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 13 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 14 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 15 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 16 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 17 minutes, relative to zolpidem.
  • the WASO is reduced by at least 18 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 19 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 20 minutes, relative to zolpidem.
  • the WASO is reduced by at least 21 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 22 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 23 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 24 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by at least 25 minutes, relative to zolpidem.
  • the WASO is reduced by about 1 minute, relative to zolpidem. In some embodiments, the WASO is reduced by about 2 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 3 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 4 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 5 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 6 minutes, relative to zolpidem. In some
  • the WASO is reduced by about 7 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 8 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 9 minutes, relative to baseline. In some embodiments, the WASO is reduced by about 10 minutes, relative to zolpidem.
  • the WASO is reduced by about 11 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 12 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 13 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 14 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 15 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 16 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 17 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 18 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 19 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 20 minutes, relative to zolpidem.
  • the WASO is reduced by about 21 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 22 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 23 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 24 minutes, relative to zolpidem. In some embodiments, the WASO is reduced by about 25 minutes, relative to zolpidem.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 7 minutes, relative to zolpidem.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by at least 6 minutes, relative to zolpidem. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by at least 7 minutes, relative to zolpidem.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 10 minutes, relative to zolpidem. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WASO is reduced by about 15 minutes, relative to zolpidem.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the 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 a subject and the WASO is reduced by at least 15 minutes, relative to zolpidem.
  • the subject has insomnia.
  • a method of reducing wake after sleep onset in the second half of the night (WAS02H) 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.
  • lemborexant or a pharmaceutically acceptable salt thereof for use in reducing WAS02H 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.
  • the WAS02H is reduced for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days.
  • the WAS02H is reduced for at least 1 day.
  • the WAS02H is reduced for at least 2 days.
  • the WAS02H is reduced for at least 3 days.
  • the WAS02H is reduced for at least 4 days.
  • the WAS02H is reduced for at least 5 days. In some embodiments, the WAS02H is reduced for at least 5 days.
  • the WAS02H is reduced for at least 6 days. In some embodiments, the WAS02H is reduced for at least 6 days.
  • the WAS02H is reduced for at least 7 days. In some embodiments, the WAS02H is reduced for at least 7 days.
  • the WAS02H is reduced for at least 8 days. In some embodiments, the WAS02H is reduced for at least 8 days.
  • the WAS02H is reduced for at least 9 days. In some embodiments, the WAS02H is reduced for at least 9 days.
  • the WAS02H is reduced for at least 10 days.
  • the WAS02H is reduced for at least 11 days. In some embodiments, the WAS02H is reduced for at least 12 days. In some embodiments, the WAS02H is reduced for at least 13 days. In some embodiments, the WAS02H is reduced for at least 14 days. In some embodiments, the WAS02H is reduced for at least 15 days. In some embodiments, the WAS02H is reduced for at least 16 days. In some embodiments, the WAS02H is reduced for at least 17 days. In some embodiments, the WAS02H is reduced for at least 18 days. In some embodiments, the WAS02H is reduced for at least 19 days.
  • the WAS02H is reduced for at least 20 days. In some embodiments, the WAS02H is reduced for at least 21 days. In some embodiments, the WAS02H is reduced for at least 22 days. In some embodiments, the WAS02H is reduced for at least 23 days. In some embodiments, the WAS02H is reduced for at least 24 days. In some embodiments, the WAS02H is reduced for at least 25 days. In some embodiments, the WAS02H is reduced for at least 26 days. In some embodiments, the WAS02H is reduced for at least 27 days. In some embodiments, the WAS02H is reduced for at least 28 days. In some embodiments, the WAS02H is reduced for at least 29 days. In some embodiments, the WAS02H is reduced for at least 30 days.
  • the WAS02H is reduced for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 1 day, relative to baseline. In some embodiments, the WAS02H is reduced for at least 2 days, relative to baseline. In some embodiments, at least 1 day, relative to baseline. In some embodiments, the WAS02H is reduced for at least 2 days, relative to baseline. In some embodiments, at least 1 day, relative
  • the WAS02H is reduced for at least 3 days, relative to baseline.
  • the WAS02H is reduced for at least 4 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 5 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 6 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 7 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 8 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 9 days, relative to baseline. In some
  • the WAS02H is reduced for at least 10 days, relative to baseline.
  • the WAS02H is reduced for at least 11 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 12 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 13 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 14 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 15 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 16 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 17 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 18 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 19 days, relative to baseline.
  • the WAS02H is reduced for at least 20 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 21 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 22 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 23 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 24 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 25 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 26 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 27 days, relative to baseline.
  • the WAS02H is reduced for at least 28 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 29 days, relative to baseline. In some embodiments, the WAS02H is reduced for at least 30 days, relative to baseline.
  • the WAS02H is reduced for at least one month.
  • the WAS02H is reduced for at least two months. In some embodiments, the WAS02H is reduced for at least three months. In some embodiments, the WAS02H is reduced for at least 6 months. In some embodiments, the WAS02H is reduced for at least 9 months. In some embodiments, the WAS02H is reduced for at least 12 months. In some embodiments, the WAS02H is reduced for at least 18 months. In some embodiments, the WAS02H is reduced for 2 years or more.
  • the WAS02H is reduced for at least one month, relative to baseline. In some embodiments, the WAS02H is reduced for at least two months, relative to baseline. In some embodiments, the WAS02H is reduced for at least three months, relative to baseline. In some embodiments, the WAS02H is reduced for at least 6 months, relative to baseline. In some embodiments, the WAS02H is reduced for at least 9 months, relative to baseline. In some embodiments, the WAS02H is reduced for at least 12 months, relative to baseline. In some embodiments, the WAS02H is reduced for at least 18 months, relative to baseline. In some embodiments, the WAS02H is reduced for 2 years or more, relative to baseline.
  • lemborexant or salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or salt thereof is administered to the subject for at least two months. In some
  • lemborexant or salt thereof is administered to the subject for at least three months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 9 months.
  • lemborexant or salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or salt thereof is administered to the subject for two years or more.
  • the WAS02H is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes, relative to baseline.
  • the WAS02H is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, 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, relative to baseline.
  • the WAS02H is reduced by at least 1 minute, relative to baseline. In some embodiments, the WAS02H is reduced by at least 2 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 3 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 4 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 5 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 6 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 7 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 8 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 9 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 10 minutes, relative to baseline.
  • the WAS02H is reduced by at least 11 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 12 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 13 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 14 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 15 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 16 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 17 minutes, relative to baseline. In some embodiments, the
  • WAS02H is reduced by at least 18 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 19 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 20 minutes, relative to baseline.
  • the WAS02H is reduced by at least 21 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 22 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 23 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 24 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 25 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 26 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 27 minutes, relative to baseline. In some embodiments, the
  • WAS02H is reduced by at least 28 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 29 minutes, relative to baseline.
  • the WAS02H is reduced by at least 30 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 31 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 32 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 33 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 34 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 35 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 36 minutes, relative to baseline. In some embodiments, the
  • WAS02H is reduced by at least 37 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 38 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 39 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 40 minutes, relative to baseline.
  • the WAS02H is reduced by at least 41 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 42 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 43 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 44 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by at least 45 minutes, relative to baseline.
  • the WAS02H is reduced by about 1 minute, relative to baseline. In some embodiments, the WAS02H is reduced by about 2 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 3 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 4 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 5 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 6 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 7 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 8 minutes, relative to baseline.
  • the WAS02H is reduced by about 9 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 10 minutes, relative to baseline. [0263] In some embodiments, the WAS02H is reduced by about 11 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 12 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 13 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 14 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 15 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 16 minutes, relative to baseline.
  • the WAS02H is reduced by about 17 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 18 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 19 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 20 minutes, relative to baseline.
  • the WAS02H is reduced by about 21 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 22 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 23 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 24 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 25 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 26 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 27 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 28 minutes, relative to baseline.
  • the WAS02H is reduced by about 29 minutes, relative to baseline. [0265] In some embodiments, the WAS02H is reduced by about 30 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 31 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 32 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 33 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 34 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 35 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 36 minutes, relative to baseline.
  • the WAS02H is reduced by about 37 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 38 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 39 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 40 minutes, relative to baseline.
  • the WAS02H is reduced by about 41 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 42 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 43 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 44 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 45 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced 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 a subject and the WAS02H is reduced by about 30 minutes, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H 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 a subject and the WAS02H is reduced by at least 30 minutes, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced 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 a subject and the WAS02H is reduced by about 37 minutes, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H 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 a subject and the sWAS02H is reduced by at least 37 minutes, relative to baseline.
  • the WAS02H is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes, relative to placebo.
  • the WAS02H is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, at least 26 minutes, at least 27 minutes, at least 28 minutes, at least 29 minutes, at least 30 minutes, at least 31 minutes, at least 32 minutes, at least 33 minutes, at least 34 minutes, or at least 35 minutes, relative to placebo.
  • the WAS02H is reduced by at least 1 minute, relative to placebo. In some embodiments, the WAS02H is reduced by at least 2 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 3 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 4 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 5 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 6 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 7 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 8 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 9 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 10 minutes, relative to placebo.
  • the WAS02H is reduced by at least 11 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 12 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 13 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 14 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 15 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 16 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 17 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 18 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 19 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 20 minutes, relative to placebo.
  • the WAS02H is reduced by at least 21 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 22 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 23 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 24 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 25 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 26 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 27 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 28 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 29 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 30 minutes, relative to placebo.
  • the WAS02H is reduced by at least 31 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 32 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 33 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 34 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by at least 35 minutes, relative to placebo.
  • the WAS02H is reduced by about 1 minute, relative to placebo. In some embodiments, the WAS02H is reduced by about 2 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 3 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 4 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 5 minutes, relative to placebo. In some embodiments,
  • the WAS02H is reduced by about 6 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 7 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 8 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 9 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 10 minutes, relative to placebo.
  • the WAS02H is reduced by about 11 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 12 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 13 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 14 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 15 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 16 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 17 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 18 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 19 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 20 minutes, relative to placebo.
  • the WAS02H is reduced by about 21 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 22 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 23 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 24 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 25 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 26 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 27 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 28 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 29 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 30 minutes, relative to placebo.
  • the WAS02H is reduced by about 31 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 32 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 33 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 34 minutes, relative to placebo. In some embodiments, the WAS02H is reduced by about 35 minutes, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by about 16 minutes, relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by about 21 minutes, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by at least 16 minutes, relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by at least 21 minutes, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H 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 the WAS02H is reduced by about 28 minutes, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by at least 17 minutes, relative to placebo. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by at least 28 minutes, relative to placebo.
  • the WAS02H is reduced by at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes, at least 75 minutes, at least 90 minutes, at least 120 minutes, at least 150 minutes, or at least 180 minutes, relative to zolpidem.
  • the WAS02H is reduced by at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, at least 21 minutes, at least 22 minutes, at least 23 minutes, at least 24 minutes, at least 25 minutes, relative to zolpidem.
  • the WAS02H is reduced by at least 1 minute, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 2 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 3 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 4 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 5 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 6 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 7 minutes, relative to zolpidem.
  • the WAS02H is reduced by at least 8 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 9 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 10 minutes, relative to zolpidem.
  • the WAS02H is reduced by at least 11 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 12 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 13 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 14 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 15 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 16 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 17 minutes, relative to zolpidem. In some embodiments, the
  • WAS02H is reduced by at least 18 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 19 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 20 minutes, relative to zolpidem.
  • the WAS02H is reduced by at least 21 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 22 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 23 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 24 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by at least 25 minutes, relative to zolpidem.
  • the WAS02H is reduced by about 1 minute, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 2 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 3 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 4 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 5 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 6 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 7 minutes, relative to zolpidem.
  • the WAS02H is reduced by about 8 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 9 minutes, relative to baseline. In some embodiments, the WAS02H is reduced by about 10 minutes, relative to zolpidem. [0289] In some embodiments, the WAS02H is reduced by about 11 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 12 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 13 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 14 minutes, relative to zolpidem.
  • the WAS02H is reduced by about 15 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 16 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 17 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 18 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 19 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 20 minutes, relative to zolpidem.
  • the WAS02H is reduced by about 21 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 22 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 23 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 24 minutes, relative to zolpidem. In some embodiments, the WAS02H is reduced by about 25 minutes, relative to zolpidem.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by about 6 minutes, relative to zolpidem.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by at least 6 minutes, relative to zolpidem.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by about 8 minutes, relative to zolpidem. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by about 13 minutes, relative to zolpidem.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by at least 8 minutes, relative to zolpidem. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the WAS02H is reduced by at least 13 minutes, relative to zolpidem.
  • the subject has insomnia.
  • a method of improving sleep efficiency (SE) in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof.
  • the SE is improved for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, or at least 30 days. In some embodiments, the SE is improved for at least 1 day.
  • the SE is improved for at least 2 days. In some embodiments, the SE is improved for at least 3 days. In some embodiments, the SE is improved for at least 4 days. In some embodiments, the SE is improved for at least 5 days. In some embodiments, the SE is improved for at least 6 days. In some embodiments, the SE is improved for at least 7 days. In some embodiments, the SE is improved for at least 8 days. In some embodiments, the SE is improved for at least 9 days. In some embodiments, the SE is improved for at least 10 days.
  • the SE is improved for at least 11 days. In some embodiments, the SE is improved for at least 12 days. In some embodiments, the SE is improved for at least 13 days. In some embodiments, the SE is improved for at least 14 days. In some embodiments, the SE is improved for at least 15 days. In some embodiments, the SE is improved for at least 16 days.
  • the SE is improved for at least 17 days. In some embodiments, the SE is improved for at least 18 days. In some embodiments, the SE is improved for at least 19 days.
  • the SE is improved for at least 20 days. In some embodiments, the SE is improved for at least 21 days. In some embodiments, the SE is improved for at least 22 days. In some embodiments, the SE is improved for at least 23 days. In some embodiments, the SE is improved for at least 24 days. In some embodiments, the SE is improved for at least 25 days.
  • the SE is improved for at least 26 days. In some embodiments, the SE is improved for at least 27 days. In some embodiments, the SE is improved for at least 28 days. In some embodiments, the SE is improved for at least 29 days. In some embodiments, the SE is improved for at least 30 days.
  • the SE is improved for at least one month. In some embodiments, the SE is improved for at least two months. In some embodiments, the SE is improved for at least three months. In some
  • the SE is improved for at least 6 months. In some embodiments, the SE is improved for at least 9 months. In some embodiments, the SE is improved for at least 12 months. In some embodiments, the SE is improved for at least 18 months. In some embodiments, the SE is improved for 2 years or more.
  • the SE is improved for at least one month. In some embodiments, the SE is improved for at least two months, relative to baseline. In some embodiments, the SE is improved for at least three months, relative to baseline. In some embodiments, the SE is improved for at least 6 months, relative to baseline. In some embodiments, the SE is improved for at least 9 months, relative to baseline. In some embodiments, the SE is improved for at least 12 months, relative to baseline. In some embodiments, the SE is improved for at least 18 months, relative to baseline. In some embodiments, the SE is improved for 2 years or more, relative to baseline.
  • lemborexant or salt thereof is administered to the subject for at least one month. In some embodiments, lemborexant or salt thereof is administered to the subject for at least two months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least three months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 6 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 9 months.
  • lemborexant or salt thereof is administered to the subject for at least 12 months. In some embodiments, lemborexant or salt thereof is administered to the subject for at least 18 months. In some embodiments, lemborexant or salt thereof is administered to the subject for two years or more.
  • the SE is improved by at least 1 %, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, or at least 50%, relative to baseline. In some embodiments, the SE is improved by at least 1 %, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11 %, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21 %, at least 22%, at least 23%, at least 24%, or at least 25%, relative to baseline.
  • the SE is improved by at least 1 %, relative to baseline. In some embodiments, the SE is improved by at least 2%, relative to baseline. In some embodiments, the SE is improved by at least 3%, relative to baseline. In some embodiments, the SE is improved by at least 4%, relative to baseline. In some embodiments, the SE is improved by at least 5%, relative to baseline. In some embodiments, the SE is improved by at least 6%, relative to baseline. In some embodiments, the SE is improved by at least 7%, relative to baseline. In some embodiments, the SE is improved by at least 8%, relative to baseline. In some embodiments, the SE is improved by at least 9%, relative to baseline.
  • the SE is improved by at least 10%, relative to baseline. In some embodiments, the SE is improved by at least 11 %, relative to baseline. In some embodiments, the SE is improved by at least 12%, relative to baseline. In some embodiments, the SE is improved by at least 13%, relative to baseline. In some embodiments, the SE is improved by at least 14%, relative to baseline. In some embodiments, the SE is improved by at least 15%, relative to baseline. In some embodiments, the SE is improved by at least 16%, relative to baseline. In some embodiments, the SE is improved by at least 17%, relative to baseline. In some embodiments, the SE is improved by at least 18%, relative to baseline. In some embodiments, the SE is improved by at least 19%, relative to baseline.
  • the SE is improved by at least 20%, relative to baseline. In some embodiments, the SE is improved by at least 21 %, relative to baseline. In some embodiments, the SE is improved by at least 22%, relative to baseline. In some embodiments, the SE is improved by at least 23%, relative to baseline. In some embodiments, the SE is improved by at least 24%, relative to baseline. In some embodiments, the SE is improved by at least 25%, relative to baseline.
  • the SE is improved by about 1 %, relative to baseline. In some embodiments, the SE is improved by about 2%, relative to baseline. In some embodiments, the SE is improved by about 3%, relative to baseline. In some embodiments, the SE is improved by about 4%, relative to baseline. In some embodiments, the SE is improved by about 5%, relative to baseline. In some embodiments, the SE is improved by about 6%, relative to baseline. In some embodiments, the SE is improved by about 7%, relative to baseline. In some embodiments, the SE is improved by about 8%, relative to baseline. In some embodiments, the SE is improved by about 9%, relative to baseline.
  • the SE is improved by about 10%, relative to baseline. In some embodiments, the SE is improved by about 11 %, relative to baseline. In some embodiments, the SE is improved by about 12%, relative to baseline. In some embodiments, the SE is improved by about 13%, relative to baseline. In some embodiments, the SE is improved by about 14%, relative to baseline. In some embodiments, the SE is improved by about 15%, relative to baseline. In some embodiments, the SE is improved by about 16%, relative to baseline. In some embodiments, the SE is improved by about 17%, relative to baseline. In some embodiments, the SE is improved by about 18%, relative to baseline. In some embodiments, the SE is improved by about 19%, relative to baseline.
  • the SE is improved by about 20%, relative to baseline. In some embodiments, the SE is improved by about 21 %, relative to baseline. In some embodiments, the SE is improved by about 22%, relative to baseline. In some embodiments, the SE is improved by about 23%, relative to baseline. In some embodiments, the SE is improved by about 24%, relative to baseline. In some embodiments, the SE is improved by about 25%, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at least 12%, relative to baseline.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 12%, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at least 14%, relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at least 15%, relative to baseline.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 14%, relative to baseline. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 15%, relative to baseline.
  • the SE is improved by at least 1 %, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, or at least 50%, relative to placebo. In some embodiments, the SE is improved by at least 1 %, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11 %, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21 %, at least 22%, at least 23%, at least 24%, or at least 25%, relative to placebo.
  • the SE is improved by at least 1 %, relative to placebo. In some embodiments, the SE is improved by at least 2%, relative to placebo. In some embodiments, the SE is improved by at least 3%, relative to placebo. In some embodiments, the SE is improved by at least 4%, relative to placebo. In some embodiments, the SE is improved by at least 5%, relative to placebo.
  • the SE is improved by at least 6%, relative to placebo. In some embodiments, the SE is improved by at least 7%, relative to placebo. In some embodiments, the SE is improved by at least 8%, relative to placebo. In some embodiments, the SE is improved by at least 9%, relative to placebo. In some embodiments, the SE is improved by at least 10%, relative to placebo.
  • the SE is improved by at least 11 %, relative to placebo. In some embodiments, the SE is improved by at least 12%, relative to placebo. In some embodiments, the SE is improved by at least 13%, relative to placebo. In some embodiments, the SE is improved by at least 14%, relative to placebo. In some embodiments, the SE is improved by at least 15%, relative to placebo.
  • the SE is improved by at least 16%, relative to placebo. In some embodiments, the SE is improved by at least 17%, relative to placebo. In some embodiments, the SE is improved by at least 18%, relative to placebo. In some embodiments, the SE is improved by at least 19%, relative to placebo. In some embodiments, the SE is improved by at least 20%, relative to placebo.
  • the SE is improved by at least 21 %, relative to placebo. In some embodiments, the SE is improved by at least 22%, relative to placebo. In some embodiments, the SE is improved by at least 23%, relative to placebo. In some embodiments, the SE is improved by at least 24%, relative to placebo. In some embodiments, the SE is improved by at least 25%, relative to placebo.
  • the SE is improved by about 1 %, relative to placebo. In some embodiments, the SE is improved by about 2%, relative to placebo. In some embodiments, the SE is improved by about 3%, relative to placebo. In some embodiments, the SE is improved by about 4%, relative to placebo. In some embodiments, the SE is improved by about 5%, relative to placebo.
  • the SE is improved by about 6%, relative to placebo. In some embodiments, the SE is improved by about 7%, relative to placebo. In some embodiments, the SE is improved by about 8%, relative to placebo. In some embodiments, the SE is improved by about 9%, relative to placebo. In some embodiments, the SE is improved by about 10%, relative to placebo.
  • the SE is improved by about 11 %, relative to placebo. In some embodiments, the SE is improved by about 12%, relative to placebo. In some embodiments, the SE is improved by about 13%, relative to placebo. In some embodiments, the SE is improved by about 14%, relative to placebo. In some embodiments, the SE is improved by about 15%, relative to placebo.
  • the SE is improved by about 16%, relative to placebo. In some embodiments, the SE is improved by about 17%, relative to placebo. In some embodiments, the SE is improved by about 18%, relative to placebo. In some embodiments, the SE is improved by about 19%, relative to placebo. In some embodiments, the SE is improved by about 20%, relative to placebo.
  • the SE is improved by about 21 %, relative to placebo. In some embodiments, the SE is improved by about 22%, relative to placebo. In some embodiments, the SE is improved by about 23%, relative to placebo. In some embodiments, the SE is improved by about 24%, relative to placebo. In some embodiments, the SE is improved by about 25%, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at least 7%, relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at least 9%, relative to placebo.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 7%, relative to placebo. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at about 9%, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at least 8%, 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 the SE is improved by at least 8%, relative to placebo.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 8%, 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 the SE is improved by about 11 %, relative to placebo.
  • the SE is improved by at least 1 %, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, or at least 50%, relative to zolpidem. In some embodiments, the SE is improved by at least 1 %, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11 %, at least 12%, at least 13%, at least 14%, or at least 15, relative to zolpidem.
  • the SE is improved by at least 1 %, relative to zolpidem. In some embodiments, the SE is improved by at least 2%, relative to zolpidem. In some embodiments, the SE is improved by at least 3%, relative to zolpidem. In some embodiments, the SE is improved by at least 4%, relative to zolpidem. In some embodiments, the SE is improved by at least 5%, relative to zolpidem.
  • the SE is improved by at least 6%, relative to zolpidem. In some embodiments, the SE is improved by at least 7%, relative to zolpidem. In some embodiments, the SE is improved by at least 8%, relative to zolpidem. In some embodiments, the SE is improved by at least 9%, relative to zolpidem. In some embodiments, the SE is improved by at least 10%, relative to zolpidem.
  • the SE is improved by at least 11 %, relative to zolpidem. In some embodiments, the SE is improved by at least 12%, relative to zolpidem. In some embodiments, the SE is improved by at least 13%, relative to zolpidem. In some embodiments, the SE is improved by at least 14%, relative to zolpidem. In some embodiments, the SE is improved by at least 15%, relative to zolpidem.
  • the SE is improved by about 1 %, relative to zolpidem. In some embodiments, the SE is improved by about 2%, relative to zolpidem. In some embodiments, the SE is improved by about 3%, relative to zolpidem. In some embodiments, the SE is improved by about 4%, relative to zolpidem. In some embodiments, the SE is improved by about 5%, relative to zolpidem.
  • the SE is improved by about 6%, relative to zolpidem. In some embodiments, the SE is improved by about 7%, relative to zolpidem. In some embodiments, the SE is improved by about 8%, relative to zolpidem. In some embodiments, the SE is improved by about 9%, relative to zolpidem. In some embodiments, the SE is improved by about 10%, relative to zolpidem.
  • the SE is improved by about 11 %, relative to zolpidem. In some embodiments, the SE is improved by about 12%, relative to zolpidem. In some embodiments, the SE is improved by about 13%, relative to zolpidem. In some embodiments, the SE is improved by about 14%, relative to zolpidem. In some embodiments, the SE is improved by about 15%, relative to zolpidem.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at least 2%, relative to zolpidem. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at least 3%, relative to zolpidem.
  • 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 2%, relative to zolpidem. In some embodiments, 5 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at about 4%, relative to zolpidem.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by at least 4%, relative to zolpidem.
  • 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 4%, relative to zolpidem. In some embodiments, 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof is administered to a subject and the SE is improved by about 5%, relative to zolpidem.
  • Embodiment 1 A method of reducing subjective sleep onset latency (sSOL) in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the sSOL is reduced, relative to baseline, for at least one month.
  • sSOL subjective sleep onset latency
  • Embodiment 2 The method according to embodiment 1 , wherein the sSOL is reduced, relative to baseline, for at least six months.
  • Embodiment 3 The method according to embodiment 1 , wherein lemborexant or salt thereof is administered to the subject for at least one month.
  • Embodiment 4 The method according to embodiment 2, wherein lemborexant or salt thereof is administered to the subject for at least six months.
  • Embodiment 5 The method according to embodiment 1 , wherein the sSOL is reduced by at least 20 minutes.
  • Embodiment 6 The method according to embodiment 1 , wherein the sSOL is 40 minutes or less.
  • Embodiment 7 The method according to embodiment 6, wherein the sSOL is 25 minutes or less.
  • Embodiment 8 The method according to 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 the sSE is increased, relative to baseline, for at least one month.
  • sSE subjective sleep efficiency
  • Embodiment 10 The method according to embodiment 9, wherein the sSE is increased, relative to baseline, for at least six months.
  • Embodiment 11 The method according to embodiment 9, wherein lemborexant or salt thereof is administered to the subject for at least one month.
  • Embodiment 12 The method according to embodiment 10, wherein lemborexant or salt thereof is administered to the subject for at least six months.
  • Embodiment 13 The method according to embodiment 9, wherein the sSE is improved by at least 13%.
  • Embodiment 14 The method according to embodiment 9, wherein the subject has insomnia.
  • Embodiment 15 A method of reducing subjective wake after sleep onset (sWASO) in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the sWASO is reduced, relative to baseline, for at least one month.
  • sWASO subjective wake after sleep onset
  • Embodiment 16 The method according to embodiment 15, wherein the sWASO is reduced, relative to baseline, for at least six months.
  • Embodiment 17 The method according to embodiment 15, wherein lemborexant or salt thereof is administered to the subject for at least one month.
  • Embodiment 18 The method according to embodiment 16, wherein lemborexant or salt thereof is administered to the subject for at least six months.
  • Embodiment 19 The method according to embodiment 15, wherein the sWASO is reduced by at least 40 minutes.
  • Embodiment 20 The method according to embodiment 15, wherein the subject has insomnia.
  • Embodiment 21 Lemborexant or a pharmaceutically acceptable salt thereof for use in reducing subjective sleep onset latency (sSOL) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of pharmaceutically acceptable salt thereof, wherein the sSOL is reduced, relative to baseline, for at least one month.
  • sSOL subjective sleep onset latency
  • Embodiment 22 The use according to embodiment 21 , wherein the sSOL is reduced, relative to baseline, for at least six months.
  • Embodiment 23 The use according to embodiment 21 , wherein lemborexant or salt thereof is administered to the subject for at least one month.
  • Embodiment 24 The use according to embodiment 22, wherein lemborexant or salt thereof is administered to the subject for at least six months.
  • Embodiment 25 The use according to embodiment 21 , wherein the sSOL is reduced by at least 20 minutes.
  • Embodiment 26 The use according to embodiment 21 , wherein the subject has insomnia.
  • Embodiment 27 Lemborexant or pharmaceutically acceptable salt thereof for improving subjective sleep efficiency (sSE) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of pharmaceutically acceptable salt thereof, wherein the sSE is increased, relative to baseline, for at least one month.
  • sSE subjective sleep efficiency
  • Embodiment 28 The use according to embodiment 27, wherein the sSE is increased, relative to baseline, for at least six months.
  • Embodiment 29 The use according to embodiment 27, wherein lemborexant or salt thereof is administered to the subject for at least one month.
  • Embodiment 30 The use according to embodiment 28, wherein lemborexant or salt thereof is administered to the subject for at least six months.
  • Embodiment 31 The use according to embodiment 27, wherein the sSE is improved by at least 13%.
  • Embodiment 32 The use according to embodiment 27, wherein the subject has insomnia.
  • Embodiment 33 Lemborexant or pharmaceutically acceptable salt thereof for reducing subjective wake after sleep onset (sWASO) in a subject, comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of pharmaceutically acceptable salt thereof, wherein the sWASO is reduced, relative to baseline, for at least one month.
  • sWASO subjective wake after sleep onset
  • Embodiment 34 The use according to embodiment 33, wherein the sWASO is reduced, relative to baseline, for at least six months.
  • Embodiment 35 The use according to embodiment 33, wherein lemborexant or salt thereof is administered to the subject for at least one month.
  • Embodiment 36 The use according to embodiment 34, wherein lemborexant or salt thereof is administered to the subject for at least six months.
  • Embodiment 37 The use according to embodiment 33, wherein the sWASO is reduced by at least 40 minutes.
  • Embodiment 38 The use according to embodiment 33, wherein the subject has insomnia.
  • Embodiment 39 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • Embodiment 40 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • Embodiment 41 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • the dosage form may be administered to a patient for at least one month, and wherein the dosage form is achievable on maintaining reduction a time to sleep onset in Subjective Sleep Onset Latency (sSOL) compared to placebo during the treatment for at least one month.
  • sSOL Subjective Sleep Onset Latency
  • Embodiment 42 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • the dosage form may be administered to a patient for six months, and wherein the dosage form is achievable on maintaining reduction a time to sleep onset in Subjective Sleep Onset Latency (sSOL) compared to placebo during the treatment through six months.
  • sSOL Subjective Sleep Onset Latency
  • Embodiment 43 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • Embodiment 44 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • Embodiment 45 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • the dosage form may be administered to a patient for at least one month, and wherein the dosage form is achievable on maintaining improvement of sleep efficiency in Subjective Sleep Efficiency (sSE) compared to placebo during the treatment for at least one month.
  • sSE Subjective Sleep Efficiency
  • Embodiment 46 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • the dosage form may be administered to a patient for six months, and wherein the dosage form is achievable on maintaining improvement of sleep efficiency in Subjective Sleep Efficiency (sSE) compared to placebo during the treatment through six months.
  • sSE Subjective Sleep Efficiency
  • Embodiment 47 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • Embodiment 48 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • Embodiment 49 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • the dosage form may be administered to a patient for at least one month, and wherein the dosage form is achievable on maintaining improvement of Wake After Sleep Onset (sWASO) compared to placebo during the treatment for at least one month.
  • sWASO Wake After Sleep Onset
  • Embodiment 50 A method for treating insomnia, comprising administering orally a dosage form comprising lemborexant or a
  • the dosage form may be administered to a patient for six months, and wherein the dosage form is achievable on maintaining improvement of Wake After Sleep Onset (sWASO) compared to placebo during the treatment through six months.
  • sWASO Wake After Sleep Onset
  • Embodiment 51 A method for treating insomnia in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep onset latency is reduced, relative to baseline, for at least one month.
  • Embodiment 52 A method for treating insomnia in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective sleep efficiency is increased, relative to baseline, for at least one month.
  • Embodiment 53 A method for treating insomnia in a subject comprising administering to the subject 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein subjective wake after sleep onset is reduced, relative to baseline, for at least one month.
  • Embodiment 54 A method of identifying a subject responsive to treatment with lemborexant or a pharmaceutically acceptable salt thereof, comprising:
  • sWASO subjective wake after sleep onset
  • Embodiment 55 The method according to embodiment 54, wherein the post-treatment period sWASO is at least 20 minutes less than the pre treatment period sWASO.
  • Embodiment 56 The method according to embodiment 54, wherein the post-treatment period sWASO is at least 30 minutes less than the pre treatment period sWASO.
  • Embodiment 57 The method according to embodiment 54, wherein, prior to administering lemborexant or a pharmaceutically acceptable salt thereof, a pre-treatment period subjective sleep efficiency (sSE) is determined.
  • sSE subjective sleep efficiency
  • Embodiment 58 The method according to embodiment 57, wherein, after administering lemborexant or a pharmaceutically acceptable salt thereof, a post-treatment period sSE is determined.
  • Embodiment 59 The method according to embodiment 55, wherein the post-treatment period sSE is improved by at least 10% relative to the pre treatment period sSE.
  • Embodiment 60 The method according to embodiment 55, wherein the post-treatment period sSE is improved by at least 14% relative to the pre treatment period sSE.
  • Embodiment 61 The method according to embodiment 54, wherein, prior to administering lemborexant or a pharmaceutically acceptable salt thereof, a pre-treatment period subjective sleep onset latency (sSOL) is determined.
  • sSOL subjective sleep onset latency
  • Embodiment 62 The method according to embodiment 61 , wherein, after administering lemborexant or a pharmaceutically acceptable salt thereof, a post-treatment period sSOL is determined.
  • Embodiment 63 The method according to embodiment 62, wherein the post-treatment period sSOL is at least 15 minutes less than the pre treatment period sSOL.
  • Embodiment 64 The method according to embodiment 62, wherein the post-treatment period sSOL is at least 20 minutes less than the pre treatment period sSOL.
  • Embodiment 65 A method for treating insomnia in a subject in need thereof, comprising:
  • post-treatment period sSOL is reduced by 15 minutes or more relative to the pre-treatment period sSOL.
  • Embodiment 66 The method according to embodiment 65, wherein the post-treatment period sSOL is reduced by 20 minutes or more relative to the pre-treatment period sSOL.
  • Embodiment 67 The method according to embodiment 65, wherein the post-treatment period sSOL is 40 minutes or less.
  • Embodiment 68 The method according to embodiment 67, wherein the post-treatment period sSOL is 25 minutes or less.
  • Embodiment 69 A method for treating insomnia in a subject in need thereof, comprising:
  • post-treatment period sSE is increased relative to the pre treatment period sSE, for at least one month
  • post-treatment period sSE is increased by 8% or more relative to the pre-treatment period sSE.
  • Embodiment 70 The method according to 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 for treating insomnia in a subject in need thereof, comprising:
  • sWASO subjective wake after sleep onset
  • post-treatment period sWASO is reduced by at least 29 minutes relative to the pre-treatment period sWASO.
  • Embodiment 72 The method according to embodiment 71 , wherein the post-treatment period sWASO is reduced by at least 40 minutes relative to the pre-treatment period sWASO.
  • Embodiment 73 A method for treating insomnia, comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof,
  • the method comprising orally administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein if the 5 mg dose is well tolerated but not effective, then the dose can be increased to 10 mg once daily,
  • the dosage form is achievable on maintaining reduction a time to sleep onset in subjective Sleep Onset Latency (sSOL) during a treatment for at least one month, and
  • sSOL subjective Sleep Onset Latency
  • sSOL is reduced by at least 15 minutes relative to baseline.
  • Embodiment 74 A method for treating insomnia, comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof,
  • the method comprising orally administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein if the 5 mg dose is well tolerated but not effective, then the dose can be increased to 10 mg once daily,
  • the dosage form is achievable on maintaining improvement of sleep efficiency in subjective Sleep Efficiency (sSE) during a treatment for at least one month, and
  • sSE subjective Sleep Efficiency
  • Embodiment 75 A method for treating insomnia, comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof,
  • the method comprising orally administering the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night and within a few minutes before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein if the 5 mg dose is well tolerated but not effective, then the dose can be increased to 10 mg once daily,
  • the dosage form is achievable on maintaining improvement of subjective Wake After Sleep Onset (sWASO) during a treatment for at least one month, and
  • sWASO subjective Wake After Sleep Onset
  • sWASO is reduced by at least 29 minutes relative to baseline.
  • Embodiment 76 A method for treating insomnia, comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof, wherein the method comprises administering orally the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night, immediately before going to bed, with at least 7 hours remaining before the planned time of awakening,
  • the daily dose can be increased to 10 mg based on clinical response and tolerability, wherein the dosage form is achievable on maintaining reduction a time to sleep onset in subjective Sleep Onset Latency (sSOL) during a treatment for at least one month.
  • sSOL subjective Sleep Onset Latency
  • Embodiment 77 The method according to Embodiment 76, wherein the dosage form is achievable on maintaining reduction a time to sleep onset in subjective Sleep Onset Latency (sSOL) during a treatment for at least six months.
  • sSOL subjective Sleep Onset Latency
  • Embodiment 78 The method according to Embodiment 76, wherein the dosage form may be administered to the patient for at least one month.
  • Embodiment 79 The method according to Embodiment 76, wherein the dosage form may be administered to the patient for at least six months.
  • Embodiment 80 The method according to Embodiment 76, wherein the sSOL is reduced by at least 15 minutes relative to baseline.
  • Embodiment 81 A method for treating insomnia, comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof,
  • the method comprises administering orally the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night, immediately before going to bed, with at least 7 hours remaining before the planned time of awakening, wherein the daily dose may be increased to 10 mg based on clinical response and tolerability,
  • the dosage form is achievable on maintaining improvement of sleep efficiency in subjective Sleep Efficiency (sSE) during a treatment for at least one month.
  • sSE subjective Sleep Efficiency
  • Embodiment 82 The method according to Embodiment 81 , the dosage form is achievable on maintaining improvement of sleep efficiency in subjective Sleep Efficiency (sSE) during a treatment for at least one month.
  • sSE subjective Sleep Efficiency
  • Embodiment 83 The method according to Embodiment 81 , wherein the dosage form may be administered to the patient for at least one month.
  • Embodiment 84 The method according to Embodiment 81 , wherein the dosage form may be administered to the patient for at least six months.
  • Embodiment 85 The method according to Embodiment 81 , wherein the sSE is improved by at least 4% relative to baseline.
  • Embodiment 86 A method for treating insomnia, comprising administering orally a dosage form comprising 5 mg or 10 mg of lemborexant or an equivalent dose of a pharmaceutically acceptable salt thereof,
  • the method comprises administering orally the 5 mg dose of lemborexant or a pharmaceutically acceptable salt thereof to a patient no more than once per night, immediately before going to bed, with at least 7 hours remaining before the planned time of awakening,
  • the daily dose may be increased to 10 mg based on clinical response and tolerability, wherein the dosage form is achievable on maintaining improvement of subjective Wake After Sleep Onset (sWASO) during a treatment for at least one month.
  • sWASO subjective Wake After Sleep Onset
  • Embodiment 87 The method according to Embodiment 86, the dosage form is achievable on maintaining improvement of sleep efficiency in subjective Sleep Efficiency (sSE) during a treatment for at least one month.
  • sSE subjective Sleep Efficiency
  • Embodiment 88 The method according to Embodiement 86, wherein the dosage form may be administered to the patient for at least one month.
  • Embodiment 89 The method according to Embodiment 86, wherein the dosage form may be administered to the patient for at least six months.
  • Embodiment 90 The method according to Embodiment 86, wherein the sWASO is reduced by at least 29 minutes relative to baseline.
  • eC-SSRS electronic Columbia-Suicide Severity Rating Scale: a self- rated suicidality scale which 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 the clinical and economic evaluation of health care, and to collect data on quality of life and preferences/utilities. The instrument comprises questions on mobility, self-care, usual activities, pain/discomfort and
  • LPS - latency to persistent sleep minutes from lights off to the first epoch of 20 consecutive epochs of non-wakefulness.
  • PGI-lnsomnia Patient Global Impression-Insomnia: a self-report assessment asking about a subject’s perception of the effects of the study drug on their sleep relative to their sleep before entering in the study.
  • SE - sleep efficiency proportion of time spent asleep per time in bed, calculated as TST/interval from lights off until lights on.
  • sSE - subjective sleep efficiency proportion of sTST per subjective time spent in bed, calculated as the interval from the time the subject reports attempting to sleep until the time the subject stopped trying to sleep for the night (operationalized as the time the subject got out of bed for the day), and time spent asleep derived from subjective time in bed minus sWASO.
  • sSOL - subjective sleep onset latency estimated minutes from the time that the subject attempted to sleep until sleep onset.
  • sTST - subjective total sleep time derived minutes of sleep from sleep onset until the time the subject stopped trying to sleep for the night.
  • sWASO - subjective wake after sleep onset sum of estimated minutes of wake during the night after initial sleep onset until the time the subject stopped trying to sleep for the night, operationalized as the time the subject got out of bed for the day.
  • T-BWSQ - Tyrer Benzodiazepine Withdrawal Symptom Questionnaire a questionnaire designed to assess withdrawal symptoms upon discontinuation study drug. Tyrer, P. et al. “The benzodiazepine withdrawal symptom
  • TST - total sleep time minutes of sleep from sleep onset until terminal awakening.
  • WASO - wake after sleep onset minutes of wake from the onset of persistent sleep until lights on.
  • WAS02H wake after sleep onset in the second half of the night:
  • WPAI-GH Work Productivity and Activity Impairment Questionnaire- General Health: collects data on absenteeism and presentism.
  • the scale comprises 6 items that are used to create the 4 scores. Outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
  • the four scores include: (1 ) percent work time missed due to health; (2) percent impairment while working due to health; (3) percent overall work impairment due to health; and (4) percent activity impairment due to health.
  • Example 1 Treatment of Subjects Having Insomnia Disorder
  • Subjects both male and female, 18 years or older, where approximately 40% of the population was aged 65 years or older, were screened to be eligible for treatment. 971 subjects were randomized for treatment, however, only 949 subjects are in the full analysis set population. The demographic information of the subject population is shown in Table 1.
  • the prerandomization phase consisted of three periods: screening, run- in, and baseline.
  • the screening period began no more than 35 days before the subject was to be randomized. Subjects were assessed based on eligibility criteria and other assessments (e.g., Sleep Disorders Screening Battery), and, if a subject was deemed to be eligible, the subject was trained on how to maintain a sleep diary and report measures of sleep parameters discussed herein. The subject then proceeded to the run-in period.
  • eligibility criteria e.g., Sleep Disorders Screening Battery
  • the run-in period began when an eligible subject was administered a placebo tablet each night immediately before bed for at least 13 nights. During the run-in period, subjects needed to remain in bed for at least 7 hours each night, and maintain a regular bedtime.
  • the randomization phase consisted of two periods: treatment period 1 and treatment period 2. The randomization phase lasted for 12 months.
  • Subjects were randomized in a double-blind manner and received either placebo, 5 mg of lemborexant, or 10 mg of lemborexant (approximately 1 :1 :1 randomization). All subjects underwent routine safety monitoring through the study, including assessments of treatment-emergent adverse events, 12-lead electrocardiograms, vital signs, weight, and clinical hematology and blood chemistry labs. Suicidality was assessed using the eC-SSRS.
  • Treatment period 1 began with the first dose of randomized study medication (placebo, 5 mg of lemborexant, or 10 mg of lemborexant). Subjects completed sleep diaries daily in the morning, within one hour of waketime. The subjects were assessed by a clinician one month, two months, three months, and six months after initiation of Treatment period 1. The following assessments were conducted:
  • Month 1 Assessment Standard safety assessments were performed on the subject. A blood sample was collected for determination of plasma concentration of lemborexant and its metabolites, and the ISI, FSS, PGI-
  • Month 2 Assessment Standard safety assessments were performed on the subject.
  • Month 3 Assessment All assessments conducted at the Month 1 Assessment were repeated.
  • Month 6 Assessment All assessments conducted at the Month 1 Assessment were repeated, and subjects completed the WPAI-GH.
  • ii. frequency of complaint is 3 or more times per week; iii. duration of complaint is 3 or more months;
  • At screening history of sSOL of 30 or more minutes on at least 3 nights per week in the previous 4 weeks and/or sWASO of 60 or more minutes on at least 3 nights per week in the previous 4 weeks.
  • At the second screening visit (Visit 2a): confirmation of current insomnia symptoms as determined from responses on the sleep diary completed on at least 7 consecutive mornings (minimum 5 of 7 for eligibility), such that sSOL was 30 or more minutes on at least 3 of the 7 nights and/or sWASO was 60 or more minutes on at least 3 of the 7 nights.
  • sSOL is 30 minutes or more on at least 3 of the 7 nights and/or sWASO is 60 minutes or more on at least 3 of the 7 nights.
  • Reported symptoms potentially related to narcolepsy that, in the clinical opinion of the investigator, indicated the need for referral for a diagnostic evaluation for the presence of narcolepsy.
  • Apnea Hypopnea Index is 10 or greater, or Periodic Limb Movements with Arousal Index is 10 or greater.
  • BAI Beck Anxiety Inventory
  • Flad current evidence of clinically significant disease e.g., cardiac; respiratory including chronic obstructive pulmonary disease, acute and/or severe respiratory depression; severe hepatic insufficiency; gastrointestinal; renal including severe renal impairment; neurological [including subjects who lack capacity and/or whose cognitive decline indicates
  • Subjects were administered a 5 mg lemborexant tablet, a 10 mg lemborexant tablet, or a lemborexant-matched placebo tablet.
  • the primary endpoint was the mean change from study baseline in subjective sleep onset latency at month 6.
  • This study had two key secondary endpoints.
  • the first key secondary endpoint was the mean change from study baseline in subjective sleep efficiency at month 6.
  • the second key secondary endpoint was the mean change from study baseline of subjective wake after sleep onset at month 6.
  • Safety endpoints for this study included the safety and tolerability of lemborexant (1 ) compared to placebo (during treatment period 1 ) and (2) in subjects exposed to lemborexant for 3, 6, 9, and 12 months.
  • the primary efficacy endpoint was the change from study baseline for mean subjective sleep onset latency, which is the estimated minutes from the time the subject attempted to sleep until sleep onset. As shown in Table 2, mean subjective sleep onset for all treatment groups was shorter than at study baseline and subjects treated with lemborexant experienced a shorter subjective sleep onset latency than subjects treated with placebo at the equivalent timepoint. See also FIG. 1 and FIG. 2.
  • Subjective total sleep time is measured in minutes.
  • Table 7 Summary and Analysis of Change from Study Baseline for Insomnia Severity Total Score (Items 1-7; Full Analysis Set).
  • insomnia severity index scores for all treatment groups decreased relative to study baseline and subjects treated with lemborexant experienced a greater decrease in insomnia severity index score than subjects treated with placebo at the equivalent timepoint.
  • Table 8 Mean Score Values of Quality of Sleep and Morning Sleepiness.
  • Table 11 shows that lemborexant is a safe and well-tolerated drug, as indicated by the low incidence of adverse events. There were no deaths reported during this study.
  • Example 2 Treatment of Subjects Having Insomnia Disorder
  • Subjects both male and female, age 55 and older, were screened to be eligible for treatment. 1006 subjects were randomized for treatment. The demographic information of the subject population is shown in Table 12.
  • This study consisted of a prerandomization phase and a randomization phase.
  • the prerandomization phase consisted of three periods: a screening period, a run-in period, and a baseline period.
  • the screening period began no more than 35 days before the subject was randomized. Once informed consent was obtained, a medical, psychiatric, and sleep history interview was conducted, which included confirmation that the subject met diagnostic criteria for insomnia disorder and that the subject complained of difficulties with sleep maintenance or early morning awakening, or both.
  • the screening assessments conducted were the Insomnia Sleep Index (ISI), the Epworth Sleepiness Scale (ESS), the STOPBang Sleep Apnea
  • Subjects were provided with a sleep diary and trained on how to record entries. After subjects completed the sleep diary on 7 consecutive mornings, and provided that the subject was still eligible to participate in the study, they attended a second clinical meeting between 10 and 17 days before the randomization phase. The subject was then fitted with a polysomnogram and trained in how to complete the postural stability assessment and cognitive performance assessment battery. Subjects then underwent an 8-hour polysomnogram recording. Within 5 minutes of waking, the postural stability assessment and cognitive assessment battery were conducted on the subject.
  • the run-in period began when eligible subjects were dispensed placebo tablets and continued until the baseline period on day 1. During the run-in period, subjects took placebo each night within 5 minutes before bedtime and subjects remained in bed for at least 7 hours.
  • the randomization phase consisted of a treatment period and a follow-up period.
  • the treatment period lasted for 31 days. Subjects were randomized in a double-blind manner and received placebo, a tablet containing 5 mg of lemborexant, a tablet containing 10 mg of lemborexant, or a tablet containing 6.25 mg of zolpidem ER. [0496] Within 5 minutes of the subject’s mean habitual bedtime, study drug was administered and an overnight polysomnogram recording was initiated. At completion of the recording the following morning (Day 2), postural stability and cognitive performance were assessed. On the Day 2 evening, subjects returned to the clinic and a blood sample was collected before administering study drug, and then study drug was administered within 5 minutes of the subject’s mean habitual bedtime. Again, a polysomnogram recording was initiated. The next morning (Day 3), postural stability and cognitive performance were assessed. A blood sample was also collected.
  • a subject who prematurely discontinued taking study drug was to return to the clinic as soon as practicable after discontinuing study drug. If the subject discontinued due to an adverse event, the adverse event must have been followed to resolution or for 2 weeks, whichever came first. Additionally, subjects who discontinued early underwent a urine drug test.
  • Subjects were administered two tablets each day according to the treatment group to which the subject was randomized:
  • lemborexant treatment group 1 zolpidem ER- matched placebo tablet and 1 lemborexant 5 mg tablet.
  • placebo 1 zolpidem ER-matched placebo tablet and 1 lemborexant-matched placebo tablet.
  • the study had a primary endpoint, several key secondary endpoints, and a number of additional secondary endpoints.
  • the primary endpoint was to determine the change from baseline for mean latency to persistent sleep on days 29 and 30 of 5 mg or 10 mg
  • One key secondary endpoint was to determine the change from baseline for mean sleep efficiency on Days 29 and 30 after administration of 5 mg or 10 mg of lemborexant, compared to placebo.
  • Another key secondary endpoint was to determine the change from baseline for mean wake after sleep onset on Days 29 and 30 after administration of 5 mg or 10 mg of lemborexant, compared to placebo.
  • Another key secondary endpoint was to determine the change from baseline for mean wake after sleep onset in the second half of the night on Days 29 and 30 after administration of 5 mg or 10 mg of lemborexant compared to administration of 6.25 mg of zolpidem ER.
  • An exemplary additional secondary endpoint is the change from baseline on the postural stability test of mean units of body sway on Days 2 and 3 after administration of 5 mg or 10 mg of lemborexant compared to zolpidem. Inclusion Criteria
  • At screening reported habitual bedtime, defined as the time the subject attempted to sleep, between 21 :00 and 24:00 and habitual waketime between 05:00 and 09:00. • At screening and at check-in before the first polysomnogram during the run-in period: ISI score greater than or equal to 13.
  • sWASO was greater than or equal to 60 minutes on at least 3 of the 7 nights.
  • insomnia a current diagnosis of sleep-related breathing disorder (including obstructive sleep apnea with or without continuous positive airway pressure treatment), periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or narcolepsy, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia as follows:
  • BAI Beck Anxiety Inventory
  • Flad current evidence of clinically significant disease eg, cardiac; respiratory including chronic obstructive pulmonary disease, acute and/or severe respiratory depression;
  • gastrointestinal including severe hepatic impairment; renal including severe renal impairment; neurological including myasthenia gravis; psychiatric disease; malignancy within the past 5 years other than adequately treated basal cell carcinoma) or chronic pain that, in the opinion of the investigator, could have affected the subject’s safety or interfered with the study assessments, including the ability to perform tasks on the cognitive PAB.
  • Transmeridian travel across more than 3 time zones in the 2 weeks before screening, or between screening and baseline, or plans to travel across more than 3 time zones during the study.
  • Table 18 Summary and Analysis of Change from Study Baseline for Subjective Sleep Onset Latency (Full Analysis Set; with data handling rules).
  • Table 19 Summary and Analysis of Change from Study Baseline for Subjective Sleep Efficiency (Full Analysis Set; with data handling rules).
  • Table 20 Summary and Analysis of Change from Study Baseline for Subjective Wake After Sleep Onset (Full Analysis Set; with data handling rules).
  • Table 22 Summary and Analysis of Change from Study Baseline for Insomnia Severity Total Score (Items 1-7; Full Analysis Set).
  • Table 23 Summary and Analysis of Change from Study Baseline for Insomnia Severity Daytime Functioning (Items 4-7; Full Analysis Set).
  • Table 24 Summary and Analysis of Change from Study Baseline for Body Sway Upon Awakening in Morning (extreme values removed; Full Analysis Set).
  • Table 29 shows that lemborexant is a safe and well-tolerated drug, as indicated by the low incidence of adverse events. There were no deaths reported during this study.
  • FIGs. 11 A-11 D show that, after the first 2 nights of treatment, treatment with zolpidem ER resulted in significantly worse performance than placebo and 5 mg of treatment on 3 of the 4 domains of the Cognitive Performance Assessment Battery, and on 2 of the 4 domains versus 10 mg lemborexant. In contrast, neither dose of lemborexant differed from placebo on cognitive tests at either point.
  • FIG. 12 shows that treatment with lemborexant (both doses) resulted in a greater reduction in the length of long awakenings than treatment with zolpidem ER, relative to placebo.
  • FIG. 15 shows that treatment with lemborexant (both doses) resulted in a greater increase in non-REM sleep compared to treatment with placebo and zolpidem ER.
  • FIG. 16 shows that treatment with lemborexant (both doses) resulted in a greater mean decrease in REM latency compared to treatment with placebo and zolpidem ER.
  • Example 1 The data collected in studies described in Example 1 and Example 2 were pooled and the response of each subject was analyzed.
  • Table 30 Summary and Analysis of Proportion of Subjective Sleep Onset Latency Responders with Data Handling Rules (Full Analysis Set,
  • Table 31 Summary and Analysis of Proportion of Subjective Wake After Sleep Onset Responders with Data Handling Rules (Full Analysis Set, Examples 1 and 2)
  • Table 32 Summary and Analysis of Proportion of Subjects Whose Total Insomnia Severity Index Score Decreased from Baseline to Month 1 by > 7 Points (Full Analysis Set, Examples 1 and 2)
  • Table 33 Summary and Analysis of Proportion of Subjects Whose Insomnia Severity Index Total Score Decreased from Baseline to Month 1 and Was ⁇ 10 (Full Analysis Set, Examples 1 and 2)
  • Table 32 provides the summary and analysis of responders, defined as those subjects whose Total ISI Score decreased at the end of month 1 by 7 or more points compared to baseline.
  • Table 33 provides the summary and analysis of responders, defined as those subjects whose ISI Total Score decreased compared to baseline and was less than 10 at month 1. For both doses of lemborexant, the difference of proportion of responders in the lemborexant group versus the placebo group was statistically significant.

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EP20832928.4A 2019-06-26 2020-06-25 Lemborexant zur behandlung von schlafstörungen Pending EP3989976A4 (de)

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PCT/US2019/039333 WO2020263253A1 (en) 2019-06-26 2019-06-26 Lemborexant for treating sleep issues
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