A Study of the Safety and Effectiveness of Suvorexant (MK-4305) for the Treatment of Insomnia in People who have Alzheimer's Disease

Overview

About this study

The purpose of this study is to examine the safety and effectiveness of suvorexant (MK-4305) to improve sleep in individuals who have Alzheimer's disease.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria

  • Diagnosis of probable Alzheimer's disease based on either 
    • The National Institute on Aging-Alzheimer's Association (NIA-AA) criteria 
    • The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, (DSM-5) criteria for Alzheimer's disease
  • Has a DSM-5 diagnosis of insomnia 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, 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
  • Is willing to stay overnight in a sleep laboratory
  • 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 
  • Able and willing to wear an activity/sleep watch on the wrist throughout the day and night
  • Based on the investigator's judgment 
    • Is able to speak, read, and understand the language of the trial staff and the informed consent form
    • Possesses the ability to respond verbally to questions, follow instructions, and complete study assessments
    • Is able to adhere to dose and visit schedules
  • Has a reliable and competent trial partner, e.g. spouse, family member, or other caregiver who
    • Signs their own informed consent after the trial has been explained to them and before screening assessments 
    • Resides with the participant overnight
    • Has had a close relationship with the participant with daily face-to-face contact at least 15 waking hours a week for at least 3 months prior to visit 1
    • Accompanies the participant to and from trial visits and stays overnight at the sleep laboratory for the three PSG visits
    • Assumes responsibility for trial medication procedures, e.g. witnessing and/or helping to administer trial medication, assessing compliance, completion of the sleep e-diary each morning, and oversight of the activity/sleep watch worn throughout the trial 
    • Answers questions regarding trial sleep quality and any distress in the trial subject's behaviors
  • Is not of childbearing potential as indicated by one of the following
    • Has reached natural menopause, defined as 
      • ≥ 45 years of age with either
        • ≥ 12 months of spontaneous amenorrhea 
        • ≥ 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 IU/L as determined by the central laboratory
    • Has had a hysterectomy
    • Has had bilateral tubal ligation
    • Has had a bilateral oophorectomy with or without a hysterectomy and greater than 6 weeks have passed since the surgery 
  • Is 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 Alzheimer's disease or insomnia 
  • Has evidence of a clinically relevant neurological disorder other than the disease being studied, i.e. probable Allzheimer's disease 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
    • 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 Alzheimer's disease 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 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
    • 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
    • Posttraumatic stress disorder
    • A psychiatric condition requiring treatment with a prohibited medication
    • 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
  • Reports 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 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  insomnia is in part the result of tobacco consumption, e.g.
      • Is unable to refrain from smoking during the night
      • Interrupts sleep to smoke or use tobacco products
      • Requires a cigarette within 30 minutes of waking in the morning
  • Has a history of excessive daytime napping 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 within 3 months of study start, 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
    • Renal disease requiring dialysis
      • 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 
    • Orthopedic
    • 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, or localized prostate cancer 
    • Or has undergone potentially curative therapy with no evidence of recurrence for ≥ 3 year post-therapy, and 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 another investigational compound or device within 30 days of signing informed consent

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Erik St Louis, M.D.

Closed for enrollment

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20265559

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