We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02750306




Registration number
NCT02750306
Ethics application status
Date submitted
21/04/2016
Date registered
21/04/2016
Date last updated
28/06/2018

Titles & IDs
Public title
Safety and Efficacy of Suvorexant (MK-4305) for the Treatment of Insomnia in Participants With Alzheimer's Disease (MK-4305-061)
Scientific 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
Secondary ID [1] 0 0
2015-003154-40
Secondary ID [2] 0 0
4305-061
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Insomnia 0 0
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Suvorexant 10 mg
Treatment: Drugs - Suvorexant 20 mg
Treatment: Drugs - Placebo

Experimental: Suvorexant 10 mg (may be increased to 20 mg) - After 2 weeks of treatment with suvorexant 10mg, the dose may be increased to suvorexant 20mg, oral, 1 tablet every night, based upon acceptable tolerability and CGI-S score of >=3

Placebo Comparator: Placebo - Placebo to suvorexant 10mg, oral, 1 tablet every night for 4 weeks. After 2 weeks of treatment, the placebo may be changed to match the suvorexant 20mg tablet based upon acceptable tolerability and CGI-S score of >= 3.


Treatment: Drugs: Suvorexant 10 mg


Treatment: Drugs: Suvorexant 20 mg


Treatment: Drugs: Placebo
Placebo to suvorexant

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in PSG-derived TST at Week 4
Timepoint [1] 0 0
Baseline and Week 4
Primary outcome [2] 0 0
Percentage of Participants Who Experienced One or More Adverse Events (AEs)
Timepoint [2] 0 0
Up to 6 weeks
Primary outcome [3] 0 0
Percentage of Participants Who Discontinued Study Drug Due to an AE
Timepoint [3] 0 0
Up to 4 weeks
Secondary outcome [1] 0 0
Change from Baseline in PSG-derived Wakefulness After Persistent Sleep Onset (WASO) at Week 4
Timepoint [1] 0 0
Baseline and Week 4

Eligibility
Key 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 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

- 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
Minimum age
50 Years
Maximum age
90 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

- 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 primary 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 3 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 6 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 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Merck Sharp & Dohme - North Ryde
Recruitment postcode(s) [1] 0 0
- North Ryde
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
Finland
State/province [7] 0 0
Espoo
Country [8] 0 0
Italy
State/province [8] 0 0
Rome
Country [9] 0 0
Korea, Republic of
State/province [9] 0 0
Seoul
Country [10] 0 0
New Zealand
State/province [10] 0 0
Wellington
Country [11] 0 0
Peru
State/province [11] 0 0
Lima
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Hoddesdon

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02750306
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02750306