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

NCT02750306 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: 4305-0612015-003154-40MK-4305-061
• Study Type: interventional
• Target: 285
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to examine the safety and efficacy of suvorexant (MK-4305) to improve sleep in individuals with Alzheimer's disease (AD). The primary hypothesis for the study is that suvorexant is superior to placebo in improving insomnia as measured by change from baseline in polysomnography (PSG)-derived total sleep time (TST) at Week 4.

Conditions

Sleep Initiation and Maintenance Disorders; Alzheimer Disease

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Polysomnography-derived Total Sleep Time (TST) at Week 4

  TST was measured at Baseline and at Week 4 in a sleep laboratory by polysomnography, during an 8-hour recording period beginning at participants' habitual bedtime.

  Baseline and Week 4

• Percentage of Participants Who Experienced One or More Adverse Events

  An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

  Up to 6 weeks

• Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event

  An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

  Up to 4 weeks

Secondary Outcomes (1)

• Change From Baseline in Polysomnography-derived Wakefulness After Persistent Sleep Onset (WASO) at Week 4

  Baseline and Week 4

Study Arms (2)

Suvorexant

EXPERIMENTAL

Participants will receive 1 suvorexant tablet every night for up to 4 weeks. After 2 weeks of double-blind treatment at 10 mg, participants' suvorexant dose may be increased to 20 mg if their Clinical Global Impression of Insomnia Severity (CGI-S) is ≥3 and investigators feel they can tolerate the increased dose.

Drug: Suvorexant

Placebo

PLACEBO COMPARATOR

Participants receive 1 placebo-matching suvorexant tablet every night for up to 4 weeks. After 2 weeks of double-blind treatment at 10 mg, participants' placebo-matching dose can be increased to 20 mg if their CGI-S is ≥3 and investigators feel they can tolerate the increased dose.

Drug: Placebo

Interventions

Suvorexant DRUG

10 mg tablet (may be increased to 20 mg tablet)

Also known as: MK-4305

Suvorexant

Placebo DRUG

Placebo to suvorexant

Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of probable Alzheimer's disease based on either a) the National Institute on Aging - Alzheimer's Association (NIA-AA) criteria or b) the Diagnostic and Statistical Manual 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 with inability to return to sleep for at least 3 nights per week for ≥ the past 3 months prior to study start, despite adequate opportunity for sleep) based on the investigator's judgment and by the participant's sleep history, as assessed by the sleep 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 bed for at least 8 hours for PSG testing
• Regular bedtime is between 8 pm and 1 am and is willing to maintain it for the duration of the trial
• Be able and willing to wear an activity/sleep watch on the wrist throughout the day and 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, and complete 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 other caregiver) who:
• a) Signs their own informed consent, after the trial has been explained to them, and before Screening assessments;
• b) Is not diagnosed with dementia;
• c) Resides with the participant overnight and has a close relationship with the participant (defined as daily face-to-face contact, at least 15 waking hours a week for at least 3 months prior to Visit 1);
• d) Accompanies the participant to and from trial visits and stays overnight at the sleep laboratory for the 3 PSG visits;
• e) Assumes responsibility for trial medication procedures (e.g., witnessing and/or helping to administer trial medication, assessing compliance), for completion of the sleep e-diary each morning, and oversight of the activity/sleep watch worn throughout the trial;
• f) Answers questions regarding the trial partner's sleep quality and trial partner's distress related to the subject's behaviors.
• If female, not of childbearing potential as indicated by one of the following: has reached natural menopause, defined as:
• a) ≥45 years of age with either: ≥12 months of spontaneous amenorrhea OR ≥6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels \> 40 IU/L as determined by the central laboratory

You may not qualify if:

• Apnea Hypopnea Index (AHI) score \> 30 or Periodic Leg Movements with Arousal per hour of Sleep (PLMA) \> 30.
• Resides in a nursing home (or similar institutional facility); assisted-living facilities are not excluded if full-time nursing care is not required.
• Has a Modified Hachinski Ischemia Scale (MHIS) Score \> 4 at Screening (i.e., evidence of vascular dementia)
• Has a known history of recent (or past) stroke that in the investigator's opinion confounds the diagnosis of either AD or insomnia
• Has evidence of a clinically relevant neurological disorder other than the disease being studied (i.e., probable AD) at Screening, including but not limited to: vascular dementia, parkinsonism, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, progressive supranuclear palsy, neurosyphilis, dementia with Lewy bodies, other types of dementia, mental retardation, hypoxic cerebral damage, cognitive impairment due to other disorders, or history of head trauma with loss of consciousness that either led to persistent cognitive deficits or in 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 the investigator:
• 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 of Continuous Positive Airway Pressure \[CPAP\] or Bilevel Positive Airway Pressure \[BIPAP\])
• Periodic Limb Movement Disorder
• Restless Legs Syndrome

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (3)

• Tao P, Svetnik V, Bliwise DL, Zammit G, Lines C, Herring WJ. Comparison of polysomnography in people with Alzheimer's disease and insomnia versus non-demented elderly people with insomnia. Sleep Med. 2023 Jan;101:515-521. doi: 10.1016/j.sleep.2022.11.027. Epub 2022 Dec 1.

  PMID: 36529106 DERIVED

• McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2020 Nov 15;11(11):CD009178. doi: 10.1002/14651858.CD009178.pub4.

  PMID: 33189083 DERIVED

• Herring WJ, Ceesay P, Snyder E, Bliwise D, Budd K, Hutzelmann J, Stevens J, Lines C, Michelson D. Polysomnographic assessment of suvorexant in patients with probable Alzheimer's disease dementia and insomnia: a randomized trial. Alzheimers Dement. 2020 Mar;16(3):541-551. doi: 10.1002/alz.12035. Epub 2020 Jan 15.

  PMID: 31944580 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Alzheimer Disease

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2016
• First Posted: April 25, 2016
• Study Start: May 23, 2016
• Primary Completion: September 30, 2018
• Study Completion: September 30, 2018
• Last Updated: October 16, 2019
• Results First Posted: October 16, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share