Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia

Inclusion Criteria (Core Study):

- Male or female, age 60 to 90 years at the time of informed consent

- Able to provide informed consent. If a participant lacks capacity to consent in the
investigator's opinion, the participant's assent should be obtained, if required in
accordance with local laws, regulations and customs, and the written informed consent
of a legal representative should be obtained (capacity to consent and definition of
legal representative should be determined in accordance with applicable local laws and
regulations).

- Documentation of diagnosis with Alzheimer's disease dementia (AD-D) on the basis of
the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines

- Mini Mental State Examination 10 to 26 at Screening

- Meets criteria for Circadian Rhythm Sleep Disorder, Irregular Sleep-Wake Type
(Diagnostic and Statistical Manual of Mental Disorders - 5th edition) and the 10th
revision of the International Classification of Diseases, as follows: Complaint by the
participant or caregiver of difficulty sleeping during the night and/or excessive
daytime sleepiness associated with multiple irregular sleep bouts during a 24-hour
period

- Frequency of complaint of sleep and wake fragmentation ≥3 days per week

- Duration of complaint of sleep and wake fragmentation ≥3 months

- During the Screening Period, mean actigraphy-derived sleep efficiency <87.5% within
the defined nocturnal sleep period and mean aWE <87.5% during the defined wake period

- Confirmation by actigraphy of a combination of sleep bouts of >10 minutes during the
wake period plus wake bouts of >10 minutes during the sleep period, totaling at least
4 bouts per 24 hours period, ≥ 3 days per week

- Ambulatory and living in the community or in a residence not classified as a skilled
nursing facility (an assisted living facility with separate living quarters where
participants and their caregivers reside is acceptable)

- Willing not to start a behavioral or other treatment program for sleep or wake
difficulties and not to start a new treatment for other symptoms of AD-D during
participation in the study

- Has a reliable and competent caregiver (or caregiver and informants) who can accompany
the participant to study visits, administer study medication on a nightly basis and
provide information on the status of the participant

- For participants taking a cholinesterase inhibitor and/or memantine, dosing regimen
must have been stable for at least 3 months

Inclusion Criteria (Extension Phase):

- Completed the Core Study (End of Study [EOS] Visit). Participants who participated in
the Core Study and completed the EOS Visit within 30 days may return to participate in
the Extension Phase as long as there are no contraindications due to ongoing adverse
events or prohibited medications.

Inclusion Criteria for Caregivers:

- Able to provide informed consent

- Spends at least 10 hours per week with the participant

- Able to meet caregiver requirements

- Willing to provide information on himself/herself regarding sleep quality and
caregiver Burden

Exclusion Criteria:

- A diagnosis of vascular dementia, dementia following multiple strokes, or any
synucleinopathy / Lewy body disorder. This includes Dementia with Lewy Bodies and
Parkinson's disease with or without dementia.

- A current diagnosis of moderate to severe obstructive sleep apnea (OSA) or central
sleep apnea, or current use of continuous positive airways pressure even if mild
severity of OSA, restless legs syndrome, periodic limb movement disorder (with
awakenings), or narcolepsy

- An Apnea-Hypopnea Index or equivalent ≥15 events/hour on diagnostic sleep study
conducted prior to Baseline or within 6 months of Screening

- A clinically significant movement disorder that would affect the differentiation of
sleep and wake by the actigraphy analytic algorithm

- Current symptoms or history during the past year of Rapid Eye Movement Behavior
Disorder or sleep-related violent behavior

- Probable Major Depression, as evidenced by score >10 on the Cornell Scale for
Depression in Dementia at Screening

- Unable to tolerate wearing the actigraph. At a minimum, participants must be able to
wear the actigraph for 5 complete days out of 7 days' data. A day will be considered
complete as long as data from 90% of the 24-hour period are able to be scored.

- Excessive caffeine use that in the opinion of the investigator contributes to the
participant's Irregular Sleep-Wake Rhythm Disorder (ISWRD)

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

- Reports habitually consuming more than 14 drinks containing alcohol per week or
habitually consumes alcohol within 3 hours before bedtime and unwilling to limit
alcohol intake to 2 or fewer drinks per day or forego having alcohol within 3 hours
before bedtime for the duration of his/her participation in the study

- Known to be human immunodeficiency virus positive

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

- A prolonged 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) (participants with evidence of bundle branch block are not excluded
if the block is not clinically significant, as documented by the investigator in the
source document)

- Current evidence of clinically significant disease that in the opinion of the
investigator(s) could affect the participant's safety or interfere with the study
assessments

- Any history of a medical or psychiatric condition other than Alzheimer's Disease
dementia that in the opinion of the investigator(s) could affect the participant's
safety or interfere with the study assessments

- History of malignancy within the previous 5 years except for adequately treated basal
cell or squamous cell skin cancer or cervical carcinoma in situ

- Any suicidal ideation with intent with or without a plan, at the time of or within 6
months of Screening, as indicated by answering "Yes" to questions 4 and 5 on the
Suicidal Ideation section of the electronic version of the Columbia Suicide Severity
Rating Scale (eC-SSRS)

- Any suicidal behavior within the past 10 years based on the eC-SSRS

- History of violence toward the caregiver or others

- Scheduled for surgery using general anesthesia during the study

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

- Used any modality of treatment for ISWRD between Screening and Randomization based on
approaches related to circadian rhythms, including phototherapy (light therapy),
melatonin and melatonin agonists

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

- Transmeridian travel across more than 3 time zones between Screening and
Randomization, or plans to travel across more than 3 time zones during the study

- Hypersensitivity to lemborexant or to its excipients

- Currently enrolled in another clinical trial, except for observational studies with no
treatment component

- Used any investigational drug or device before informed consent (ie, within 30 days or
5× the investigational drug half-life whichever is longer or 6 months for potential
disease-modifying drugs)

- Previously participated in any clinical trial of lemborexant