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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02750306
First received: April 21, 2016
Last updated: May 16, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Insomnia
Alzheimer's Disease
Drug: Suvorexant 10 mg
Drug: Suvorexant 20 mg
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Placebo-Controlled Clinical Trial to Study the Safety and Efficacy of Suvorexant (MK-4305) for the Treatment of Insomnia in Subjects With Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change from Baseline in PSG-derived TST at Week 4 [ Time Frame: Baseline and Week 4 ]
  • Percentage of Participants Who Experienced One or More Adverse Events (AEs) [ Time Frame: Up to 6 weeks ]
  • Percentage of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to 4 weeks ]

Secondary Outcome Measures:
  • Change from Baseline in PSG-derived Wakefulness After Persistent Sleep Onset (WASO) at Week 4 [ Time Frame: Baseline and Week 4 ]

Estimated Enrollment: 260
Actual Study Start Date: May 23, 2016
Estimated Study Completion Date: October 18, 2017
Estimated Primary Completion Date: October 5, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Suvorexant 10 mg (may be increased to 20 mg)
Suvorexant 10 mg, oral, 1 tablet every night for 4 weeks. After 2 weeks of treatment, the dose of suvorexant may be increased to 1 tablet of 20 mg based upon the Investigator's decision and on a Clinical Global Impressions - Severity, for Insomnia (CGI-S) score of >=3.
Drug: Suvorexant 10 mg
Other Name: MK-4305
Drug: Suvorexant 20 mg
Other Name: MK-4305
Placebo Comparator: Placebo
Placebo to suvorexant, oral, 1 tablet every night for 4 weeks. After 2 weeks of treatment the placebo may be changed to match the suvorexant 20 mg tablet based upon the Investigator's decision and on a CGI-S score of >=3.
Drug: Placebo
Placebo to suvorexant

  Eligibility

Ages Eligible for Study:   50 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 a DSM-5 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 subject'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) 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);
  • c) Accompanies the participant to and from trial visits and stays overnight at the sleep laboratory for the three PSG visits;
  • d) 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;
  • e) 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
  • 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:

  • Resides in a nursing home (or similar institutional facility)
  • 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
  • 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
  • Primary Hypersomnia
  • Excessive Daytime Sleepiness (EDS) characterized by uncharacteristic chronic and persistent sleepiness throughout the day
  • Has a clinically significant movement disorder, such as akinesia, that would affect the activity/sleep watch differentiation of sleep and wakefulness
  • In the opinion of the investigator, has difficulty sleeping primarily due to a confounding medical condition. NOTE: "Medical Conditions" may include chronic pain syndromes, 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's judgment. 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 psychotic disorder, or posttraumatic stress disorder; or,
  • A psychiatric condition requiring treatment with a prohibited medication; or,
  • Other psychiatric condition that, in the investigator's opinion, would interfere with the subject's ability to participate in the study.
  • Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator. Subjects must be excluded if they report suicidal ideation with intent, with or without a plan or method in the past 2 months or suicidal behavior in the past 6 months.
  • Has a history of alcoholism or drug dependency/abuse within the last 5 years of study start
  • 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 to bedtime
  • More than > 600 mg caffeine a day (e.g., 4 standard 8-ounce cups of brewed coffee, or consumes caffeine after 4pm (16:00)
  • Consumes the equivalent of >15 cigarettes a day and the investigator confirms that the participant's insomnia is in part the result of tobacco consumption (e.g., participants unable to refrain from smoking during the night, participants who interrupt sleep to smoke or use tobacco products, or participants who require a cigarette within 30 minutes of waking in the morning).
  • Has a history of excessive daytime napping (defined as more than 3 hours a day for more 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 or major surgery where participation in the trial would pose a significant medical risk to the subject within 3 months of study start, such as: conditions including but not limited to diabetes, hypertension, Human Immunodeficiency Virus (HIV) or other relevant infections, thyroid or endocrine disease, Chronic Obstructive Pulmonary Disease (COPD), delirium, congestive heart failure, angina, cardiac or gastrointestinal disease, or renal disease requiring dialysis. Note: controlled co-morbid conditions (including diabetes, hypertension, heart disease, etc.) are not exclusionary if stable within three months of the study start. All concomitant medications, supplements, or other substances must be kept as stable as medically possible during the trial. Urinary tract infections at study start are not exclusionary if adequately treated.
  • Major surgery including not limited to abdominal, thoracic, cardiac or orthopedic surgery, 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 six months prior to study start.
  • Has a known allergy or hypersensitivity to suvorexant or to any of the formulation components
  • Has a history of hypersensitivity or idiosyncratic reaction to more than three (3) chemical classes of drugs, including prescriptions and over-the-counter medications.
  • Has donated blood products or has had phlebotomy of >300 mL within 8 weeks of study start, or intends to donate or receive blood products during participation in the study.
  • History of malignancy ≤5 years prior to study start, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized prostate cancer, who has undergone potentially curative therapy with no evidence of recurrence for ≥ 3 year post-therapy, and who is deemed at low risk for recurrence by her/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 investigational compound or device within 30 days of signing informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02750306

Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 29 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02750306     History of Changes
Other Study ID Numbers: 4305-061
2015-003154-40 ( EudraCT Number )
MK-4305-061 ( Other Identifier: Merck protocol number )
Study First Received: April 21, 2016
Last Updated: May 16, 2017

Additional relevant MeSH terms:
Suvorexant
Alzheimer Disease
Sleep Initiation and Maintenance Disorders
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Orexin Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2017