Safety and Efficacy of Suvorexant (MK-4305) for the Treatment of Insomnia in Participants With Alzheimer's Disease (MK-4305-061)

Inclusion Criteria:

• Diagnosis of probable Alzheimer's disease based on either a) the National Institute onAging - Alzheimer's Association (NIA-AA) criteria or b) the Diagnostic and StatisticalManual of Mental Disorders, 5th Edition, (DSM-5) criteria for AD.

• Have sleep complaints that meet DSM-5 criteria for a diagnosis of insomnia (e.g.,difficulty initiating or maintaining sleep, and/or early morning awakenings withinability to return to sleep for at least 3 nights per week for ≥ the past 3 monthsprior to study start, despite adequate opportunity for sleep) based on theinvestigator's judgment and by the participant's sleep history, as assessed by thesleep items on the Insomnia Diagnostic Interview and Sleep History assessments.

• Be willing to stay overnight in a sleep laboratory and must be willing to stay in bedfor at least 8 hours for PSG testing

• Regular bedtime is between 8 pm and 1 am and is willing to maintain it for theduration of the trial

• Be able and willing to wear an activity/sleep watch on the wrist throughout the dayand night

• Based on the investigator's judgment the participant should: a) be able to speak,read, and understand the language of the trial staff and the informed consent form; b)possess the ability to respond verbally to questions, follow instructions, andcomplete study assessments; c) be able to adhere to dose and visit schedules.

• Have a reliable and competent trial partner (e.g., spouse, family member, or othercaregiver) who:

• a) Signs their own informed consent, after the trial has been explained to them, andbefore Screening assessments;

• b) Is not diagnosed with dementia;

• c) Resides with the participant overnight and has a close relationship with theparticipant (defined as daily face-to-face contact, at least 15 waking hours a weekfor at least 3 months prior to Visit 1);

• d) Accompanies the participant to and from trial visits and stays overnight at thesleep laboratory for the 3 PSG visits;

• e) Assumes responsibility for trial medication procedures (e.g., witnessing and/orhelping to administer trial medication, assessing compliance), for completion of thesleep e-diary each morning, and oversight of the activity/sleep watch worn throughoutthe trial;

• f) Answers questions regarding the trial partner's sleep quality and trial partner'sdistress related to the subject's behaviors.

• If female, not of childbearing potential as indicated by one of the following: hasreached natural menopause, defined as:

• a) ≥45 years of age with either: ≥12 months of spontaneous amenorrhea OR ≥6 months ofspontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 IU/Las determined by the central laboratory

• b) has had a hysterectomy;

• c) has had bilateral tubal ligation; or

• d) has had a bilateral oophorectomy (with or without a hysterectomy) and greater than 6 weeks have passed since the surgery

• Be willing to provide a blood sample for Apolipoprotein E (APOE) genotyping

Exclusion Criteria:

• Apnea Hypopnea Index (AHI) score > 30 or Periodic Leg Movements with Arousal per hourof Sleep (PLMA) > 30.

• Resides in a nursing home (or similar institutional facility); assisted-livingfacilities are not excluded if full-time nursing care is not required.

• Has a Modified Hachinski Ischemia Scale (MHIS) Score > 4 at Screening (i.e., evidenceof vascular dementia)

• Has a known history of recent (or past) stroke that in the investigator's opinionconfounds the diagnosis of either AD or insomnia

• Has evidence of a clinically relevant neurological disorder other than the diseasebeing studied (i.e., probable AD) at Screening, including but not limited to: vasculardementia, parkinsonism, frontotemporal dementia, Huntington's disease, amyotrophiclateral sclerosis, multiple sclerosis, progressive supranuclear palsy, neurosyphilis,dementia with Lewy bodies, other types of dementia, mental retardation, hypoxiccerebral damage, cognitive impairment due to other disorders, or history of headtrauma with loss of consciousness that either led to persistent cognitive deficits orin the opinion of the investigator confounds the diagnosis of either AD or insomnia.

• Has a history of seizures or epilepsy within the last 5 years before study start

• Has a history or diagnosis of any of the following conditions, in the opinion of theinvestigator:

• Narcolepsy

• Cataplexy (familial or idiopathic)

• Circadian Rhythm Sleep Disorder

• Parasomnia including nightmare disorder, sleep terror disorder, sleepwalking disorder

• Rapid eye movement (REM) behavior disorder

• Significant degree of sleep-related Breathing Disorder (i.e., AHI >30, and/or use ofContinuous Positive Airway Pressure [CPAP] or Bilevel Positive Airway Pressure [BIPAP])

• Periodic Limb Movement Disorder

• Restless Legs Syndrome

• Primary Hypersomnia

• Excessive Daytime Sleepiness (EDS) characterized by uncharacteristic chronic andpersistent sleepiness throughout the day

• Has a clinically significant movement disorder, such as akinesia, that would affectthe activity/sleep watch differentiation of sleep and wakefulness

• In the opinion of the investigator, has difficulty sleeping primarily due to aconfounding medical condition. NOTE: "Medical Conditions" may include chronic painsyndromes, chronic migraine, cardiac disease, nocturia (> 3 times/night), asthma,gastroesophageal reflux disease (GERD), or hot flashes.

• Has evidence of a current episode of major depression based on investigator'sjudgment. Major depression in remission is not exclusionary.

• Has any of the following based on clinician interview and DSM-5 criteria:

• Lifetime history of bipolar disorder, a primary psychotic disorder, or posttraumaticstress disorder; or,

• A psychiatric condition requiring treatment with a prohibited medication; or,

• Other psychiatric condition that, in the investigator's opinion, would interfere withthe subject's ability to participate in the study.

• Is at imminent risk of self-harm, based on clinical interview and responses on theColumbia-Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinionof the investigator. Subjects must be excluded if they report suicidal ideation withintent, with or without a plan or method in the past 2 months or suicidal behavior inthe past 6 months.

• Has a history of alcoholism or drug dependency/abuse within the last 5 years of studystart

• Has a recent history (within the 6 months prior to Screening) of regular consumption (3 or more days per week) of either:

• More than 2 alcoholic beverages per day or alcohol consumption within 3 hours prior tobedtime

• More than > 600 mg caffeine a day (e.g., 4 standard 8-ounce cups of brewed coffee, orconsumes caffeine after 4pm (16:00)

• Consumes the equivalent of >15 cigarettes a day and the investigator confirms that theparticipant's insomnia is in part the result of tobacco consumption (e.g.,participants unable to refrain from smoking during the night, participants whointerrupt sleep to smoke or use tobacco products, or participants who require acigarette within 30 minutes of waking in the morning).

• Has a history of excessive daytime napping (defined as more than 3 hours a day formore than 3 days of the week based on trial partner estimates, on average for the past 4 weeks).

• Has a recent or ongoing, uncontrolled, clinically significant medical condition ormajor surgery where participation in the trial would pose a significant medical riskto the subject within 3 months of study start, such as: conditions including but notlimited to diabetes, hypertension, Human Immunodeficiency Virus (HIV) or otherrelevant infections, thyroid or endocrine disease, Chronic Obstructive PulmonaryDisease (COPD), delirium, congestive heart failure, angina, cardiac orgastrointestinal disease, or renal disease requiring dialysis. Note: controlledco-morbid conditions (including diabetes, hypertension, heart disease, etc.) are notexclusionary if stable within 3 months of the study start. All concomitantmedications, supplements, or other substances must be kept as stable as medicallypossible during the trial. Urinary tract infections at study start are notexclusionary if adequately treated.

• Major surgery including not limited to abdominal, thoracic, cardiac or orthopedicsurgery, or any procedure requiring general anesthesia

• Has a history of hepatitis or liver disease that, in the opinion of the investigator,has been active within the 6 months prior to study start.

• Has a known allergy or hypersensitivity to suvorexant or to any of the formulationcomponents

• Has a history of hypersensitivity or idiosyncratic reaction to more than 3 chemicalclasses of drugs, including prescriptions and over-the-counter medications.

• Has donated blood products or has had phlebotomy of >300 mL within 8 weeks of studystart, or intends to donate or receive blood products during participation in thestudy.

• History of malignancy within the 5 years prior to study start, except for adequatelytreated basal cell or squamous cell skin cancer, in situ cervical cancer, localizedprostate cancer, who has undergone potentially curative therapy with no evidence ofrecurrence for >=3 year post-therapy, and who is deemed at low risk for recurrence byher/his treating physician.

• Is pregnant, is attempting to become pregnant, or is nursing children

• Has a Body Mass Index (BMI) > 40 kg/m^2

• Is currently participating or has participated in a study with an investigationalcompound or device within 30 days of signing informed consent