Study to Evaluate the Respiratory Safety of Lemborexant in Adult and Elderly Healthy Subjects and Adult and Elderly Subjects With Mild Obstructive Sleep Apnea

Healthy Volunteer (HV) Cohort:

The HV Cohort comprises a randomized, double-blind, placebo-controlled, 3-period crossover
study. Eligible healthy adult and elderly participants will be randomized to treatment
sequence A, B, or C, each consisting of 3 Treatment Periods, each of one night's duration, in
which participants will receive a single dose of lemborexant 10 milligrams (mg), or
lemborexant 25 mg, or placebo. Treatment Periods will be separated by a washout interval of
at least 14 days. A sufficient number of participants will be randomized to ensure that 8
evaluable adult participants (<65 years) and 4 evaluable elderly participants (≥65 years)
complete the study.

OSA Cohort:

The OSA Cohort comprises a randomized, double-blind, placebo-controlled, 2-period crossover
study. Adult and elderly participants with mild OSA will be randomized to treatment sequence
D or E, each consisting of 2 Treatment Periods, each of 8 nights' duration, in which
participants will receive lemborexant 10 mg or placebo. The Treatment Periods will be
separated by a washout interval of at least 14 days. A sufficient number of participants will
be randomized to ensure that 20 evaluable adult participants (<65 years) and 10 evaluable
elderly participants (≥65 years) complete the study.

Inclusion Criteria:

Participants must meet all of the following criteria to be included in this study:

- Male or female, age ≥18 years and ≤90 years at the time of informed consent

- Voluntary agreement and ability to provide written informed consent

- Reports habitually sleeping for at least 5.5 hours per night

- Agrees to stay in bed for 7 hours per night for the duration of treatment

- Reports habitual bedtime between 21:00 and 01:00

- Peripheral capillary oxygen saturation (SpO2) ≥94% assessed as part of vital signs at
Screening Visit 1

Additional Inclusion Criteria (Healthy Volunteer [HV] Cohort):

- Body mass index (BMI) less than or equal to 32 kilograms per meters squared (kg/m^2)

- On screening polysomnography (PSG) (Screening Visit 2): apnea-hypopnea index (AHI) <5

Additional Inclusion Criteria (Obstructive Sleep Apnea [OSA] Cohort):

- BMI ≤40 kg/m^2

- OSA, diagnosed according to the criteria of the International Classification of Sleep
Disorders, version 3

- On Screening PSG: AHI ≥5 to <15 (mild severity)

Exclusion Criteria:

- A current diagnosis of restless legs syndrome, periodic limb movement disorder,
circadian rhythm sleep disorder, or narcolepsy

- Reports symptoms potentially related to narcolepsy, that in the clinical opinion of
the investigator indicate the need for referral for a diagnostic evaluation for the
presence of narcolepsy

- A history of a parasomnia or parasomnia observed on the Screening PSG that in the
investigator's opinion makes the participant unsuitable for the study

- Periodic Limb Movement with Arousal Index (PLMAI) as measured on the Screening PSG:

1. Age 18 to <65 years: PLMAI ≥10

2. Age ≥65 years: PLMAI >15

- History of or suspected drug or alcohol use disorder within approximately 2 previous
years

- A positive urine drug test or breath alcohol test at Screening or Baseline, or
unwilling to refrain from use of recreational drugs during the study

- Known to be human immunodeficiency virus positive

- Active viral hepatitis (B or C) as demonstrated by positive viral serology at
Screening

- A prolonged QT/corrected QT (QTc) interval (QT interval corrected for heart rate using
Fridericia's formula [QTcF] >450 milliseconds [ms]) as demonstrated by a repeated
electrocardiogram (ECG) at Screening (repeated if initial ECG indicates a QTcF
interval >450 ms)

- Comorbid nocturia resulting in the need to get out of bed to use the bathroom more
than 3 times during the night

- Any history of medical or psychiatric condition that in the opinion of the
investigator could affect the participant's safety or interfere with the study
assessments

- Any suicidal ideation with intent to act with or without a plan, current or within 6
months before the Columbia - Suicide Severity Rating Scale (C-SSRS) administration
during the Screening (e.g., answering "Yes" to questions 4 or 5 on the Suicidal
Ideation section of the C-SSRS

- Any suicidal behavior (per the Suicidal Behavior section of the C-SSRS) within 10
years of Screening

- Scheduled for surgery during the study that requires general anesthesia or
administration of prohibited medications

- Used any prohibited prescription or over-the-counter medications within 1 week or 5
half-lives, whichever is longer, before the Screening PSG

- Hypersensitivity to lemborexant or excipients

- Currently enrolled in another interventional clinical trial or used any
investigational drug or device within 30 days or 5 times the half-life, whichever is
longer preceding informed consent

- Previously participated in other clinical trial of lemborexant

- Is unable to avoid working a night shift within 2 weeks before the Screening PSG, or
between the Screening PSG and End-of-Study

- Has travelled across 3 or more time zones in the week prior to Screening, or plans to
travel across more than 3 time zones during the study

- Clinically significant findings based on vital signs, physical examination, ECG, or
clinical laboratory tests

Additional Exclusion Criteria (HV Cohort):

- Any valid event of SpO2 <90% during the Screening PSG

- Current evidence of a clinically significant, active respiratory disorder. This
includes bronchiectasis, emphysema, asthma, chronic obstructive pulmonary disease, or
any other pulmonary disorder identified by review of medical history, physical
examination, and which in the opinion of the investigator, could compromise the
participant's safety or interfere with study assessments

- Presence of significant illness (including insomnia) that requires treatment or may
influence the study assessments (e.g., psychiatric disorders, disorders of the
gastrointestinal tract, liver, kidney, respiratory system, endocrine system,
hematological system, neurological system, cardiovascular system, or a congenital
abnormality), malignancy within the past 5 years (other than adequately treated basal
cell carcinoma or in situ carcinoma of the cervix), or chronic pain that in the
opinion of the investigator could interfere with the study assessments. Participants
for whom a sedating drug would be contraindicated for safety reasons because of the
participant's occupation or activities are also excluded

Additional Exclusion Criteria (OSA Cohort):

- SpO2 less than 80% for ≥ 5% of total sleep time during the Screening PSG

- Uses or plans to use of continuous positive airway pressure device or dental appliance
within 2 weeks of the Screening PSG (Screening Visit 2) or during the study

- Current evidence of a clinically significant, active respiratory disorder other than
OSA. This includes bronchiectasis, emphysema, asthma, chronic obstructive pulmonary
disease or any other pulmonary disorder identified by review of medical history,
physical examination, and which in the opinion of the investigator, could compromise
the participant's safety or interfere with study assessments

- Current evidence of other clinically significant disease (e.g., psychiatric disorders,
disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine
system, hematological system, neurological system, cardiovascular system, or a
congenital abnormality), malignancy within the past 5 years (other than adequately
treated basal cell carcinoma or in situ carcinoma of the cervix), or chronic pain that
in the opinion of the investigator could affect the participant's safety or interfere
with the study assessments. Participants for whom a sedating drug would be
contraindicated for safety reasons because of the participant's occupation or
activities are also excluded. Participants with insomnia disorder, who complain of
difficulties with sleep onset and/or sleep maintenance, are eligible provided that
they meet this criterion. Note that medications to treat insomnia are prohibited.