Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1)

The study is a multicenter, randomized, double-blind, placebo-controlled, active comparator,
parallel-group study of 2 dose levels of lemborexant for 30 nights in approximately 950
participants, 55 years or older with insomnia disorder. Participants will be males 65 years
or older or females 55 years or older. Approximately 60% of the participants will be age 65
years or older. The study will have 2 phases: The Prerandomization Phase and the
Randomization Phase. Including both phases, the study will last for a minimum of 65 and a
maximum of 81 days per participant.

Inclusion Criteria

1. Male age 65 years or older or female age 55 years or older at the time of informed
consent

2. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
criteria for Insomnia Disorder, as follows:

- Complains of dissatisfaction with nighttime sleep, in the form of difficulty
staying asleep and/or awakening earlier in the morning than desired despite
adequate opportunity for sleep (Note that if the complaint is limited to
difficulty initiating sleep, the participant is not eligible)

- Frequency of complaint ≥ 3 times per week

- Duration of complaint ≥ 3 months

- Associated with complaint of daytime impairment

3. History of subjective wake after sleep onset (sWASO) typically ≥ 60 minutes on at
least 3 nights per week in the previous 4 weeks

4. Reports regular time spent in bed, either sleeping or trying to sleep, between 7 and 9
hours

5. Reports habitual bedtime, defined as the time the participant attempts to sleep,
between 21:00 and 24:00 and habitual waketime between 05:00 and 09:00

6. Insomnia Severity Index (ISI) score ≥ 13

7. Confirmation of current insomnia symptoms as determined from responses on the Sleep
Diary before the second screening visit

8. Confirmation of regular bedtime and waketime as determined from responses on the Sleep
Diary

9. Confirmation of sufficient duration of time spent in bed, as determined from responses
on the Sleep Diary

10. Objective (polysomnography [PSG]) evidence of insomnia as follows:

a) Wake after sleep onset (WASO) average ≥ 60 minutes on the 2 consecutive PSGs, with
neither night < 45 minutes

11. Willing and able to comply with all aspects of the protocol, including staying in bed
for at least 7 hours each night

12. Willing not to start a behavioral or other treatment program for the treatment of
insomnia during the participant's participation in the study

Exclusion Criteria

1. A current diagnosis of sleep-related breathing disorder including obstructive sleep
apnea (with or without continuous positive airway pressure [CPAP] treatment), periodic
limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or
narcolepsy, or an exclusionary score on screening instruments to rule out individuals
with symptoms of certain sleep disorders other than insomnia as follows:

1. STOPBang score ≥5

2. International Restless Legs Scale score ≥16

3. Epworth Sleepiness Scale score >15 (scores of 11 to 15 require excessive daytime
sleepiness to be recorded in participant's Medical History)

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

3. On the Munich Parasomnia Scale (MUPS), endorsed the item that corresponds to a history
of sleep-eating or reports a history of sleep-related violent behavior, sleep-driving,
or symptoms of another parasomnia that in the investigator's opinion make the
participant unsuitable for the study

4. Apnea-Hypopnea Index > 15 or Periodic Limb Movement with Arousal Index >15 as measured
on the PSG at the second screening visit

5. Beck Depression Inventory - II (BDI-II) score >19 at Screening

6. Beck Anxiety Index (BAI) score >15 at Screening

7. Habitually naps during the day more than 3 times per week

8. Is a female of childbearing potential Note: All females will be considered to be of
childbearing potential unless they are postmenopausal (defined as amenorrheic for at
least 12 consecutive months, and are postmenopausal without other known or suspected
cause), or have been sterilized surgically (i.e., bilateral tubal ligation, total
hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before
dosing).

9. Excessive caffeine use that in the opinion of the investigator contributes to the
participant's insomnia, or habitually consumes caffeine-containing beverages after
18:00 and is unwilling to forego caffeine after 18:00 for the duration of his/her
participation in the study.

10. History of drug or alcohol dependency or abuse within approximately the previous 2
years

11. Reports habitually consuming more than 14 drinks containing alcohol per week (females)
or more than 21 drinks containing alcohol per week (males), or unwilling to limit
alcohol intake to no more than 2 drinks per day or forego having alcohol within the 3
hours before bedtime for the duration of his/her participation in the study

12. Known to be positive for human immunodeficiency virus

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

14. A prolonged QT/QTcF interval (QTcF >450 milliseconds [ms]) as demonstrated by a
repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates
a QTcF interval >450 ms)

15. Current evidence of clinically significant disease (e.g., cardiac; respiratory
including chronic obstructive pulmonary disease, acute and/or severe respiratory
depression; gastrointestinal; severe hepatic impairment; renal including severe renal
impairment; neurological including myasthenia gravis; psychiatric disease; or
malignancy within the past 5 years other than adequately treated basal cell carcinoma)
or chronic pain that in the opinion of the investigator(s) could affect the
participant's safety or interfere with the study assessments, including the ability to
perform tasks on the cognitive performance assessment battery (PAB). Participants for
whom a sedating drug would be contraindicated for safety reasons because of the
participant's occupation or activities are also excluded.

16. Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom
during the night

17. Any history of a medical or psychiatric condition that in the opinion of the
investigator(s) could affect the participant's safety or interfere with the study
assessment, including the ability to perform the PAB.

18. Any suicidal ideation with intent with or without a plan, at the time of or within 6
months before the electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
administration during the Prerandomization Phase (i.e., answering "Yes" to questions 4
or 5 on the Suicidal Ideation section of the eC-SSRS)

19. Any suicidal behavior in the past 10 years (per the Suicidal Behavior section of the
eC-SSRS)

20. Scheduled for surgery during the study

21. Used any prohibited prescription or over-the-counter concomitant medications within 1
week or 5 half lives, whichever is longer, before the first dose of study medication
(Run-in Period).

22. Used any modality of treatment for insomnia, including cognitive behavioral therapy or
marijuana within 1 week or 5 half-lives, whichever is longer, before the first dose of
study medication (Run-in Period)

23. Failed treatment with suvorexant (Belsomra®) (efficacy and/or safety) following
treatment with an appropriate dose and of adequate duration in the opinion of the
investigator

24. 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

25. A positive drug test at Screening, Run-In, or Baseline, or unwilling to refrain from
use of recreational drugs during the study

26. Hypersensitivity to lemborexant or zolpidem or to their excipients

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

28. Previously participated in any clinical trial of lemborexant