CompletedPhase 2

Efficacy and Safety of Ramelteon in Subjects With Mild to Moderate Alzheimer's Disease

A Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of 8 Week Treatment of Rozerem 8 mg (QHS) in Sleep Disturbed, Mild to Moderately Severe Alzheimer's Disease Subjects

Lead sponsor

Takeda

Asset

Ramelteon

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 8-28•Study partner/caregiver required

Primary endpoint

•Mean Nighttime Total Sleep Time

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID01-05-TL-375-061

NCT IDNCT00325728

RegistryU1111-1115-1644WHO

Timeline

Milestones

Study start2006-03-21actual

Study first posted2006-05-15estimated

Primary completion2007-08-01actual

Study completion2007-08-20actual

Last update posted2017-08-14actual

Assets

Drug assets

Ramelteon

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Clinical diagnosis of dementia of the Alzheimer's type (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised) or probable Alzheimer's disease by National Institute of Neurological and Communicative Disorders and Stroke/the Alzheimer's Disease and Related

•Disorders Association criteria.

•Female subjects must be post-menopausal.

•Stable residence with no planned move during the entire investigation period.

•Residing in the same residence with a responsible spouse, family member, or a professional caregiver who is present during the night who would agree to assume the role of the principal caregiver for the duration of the protocol period.

•Able to ingest oral medication and participate in all scheduled evaluations.

•Clinical laboratory evaluations (including clinical chemistry, hematology, and urinalysis) within the reference range as tested by the designated laboratory unless the results are deemed not clinically significant by the investigator or sponsor.

•Treatment medications for any non-excluded medications or concurrent medical conditions are stable for 30 days prior to the screening visit and medication(s) can in the investigator's judgment, remain stable throughout the duration of the study.

•Mini-Mental State Examination score of 8 to 28, inclusive.

•History of greater than or equal to 2 sleep disorder behaviors, occurring at least once weekly over the two weeks before screening.

•Actigraphy evidence shows a nighttime total sleep time of less than 7 hours per night based on at least 4 out of 7 nights of complete actigraphy data collected over the single-blind, placebo run-in period.

•Habitual bedtime of between 8 PM and 12 AM

Exclusion criteria

•Non-ambulatory, wheel chair bound or confined to bed and is without a consistent caregiver who is present during the night who could function as the primary caregiver.

•Caregiver is deemed by the investigator to be unreliable to supervise the wearing of the actigraphy, to complete the sleep log, to administer medication at the proper time, to bring the subject to the scheduled visits or to answer questions regarding the subject's condition or medication use.

•Lacks a mobile upper extremity to which to attach an actigraphy.

•Currently participating or has participated in another clinical study within the past 30 days.

•Demonstrates an unwillingness to abstain from caffeine after 2:00 PM for the duration of the clinical trial participation.

•Demonstrates an unwillingness to comply with the maximum limit of two alcoholic drinks per day and only one alcoholic drink after 6:00 PM for the duration of the protocol.

•Uses tobacco products or any other products during nightly awakenings that may interfere with the sleep wake cycle.

•History of drug abuse or tests positive for the presence of illicit drugs.

•Donated more than 400 mL of blood within the 90 days preceding the beginning of the study.

•Diastolic blood pressure greater than 95 mm Hg or a systolic pressure of greater than 160 mm Hg.

•Body mass index of greater than 36.

•Alanine transaminase level of greater than two times the upper limit of normal, active liver disease, jaundice or any clinically significant abnormal laboratory findings as determined by the investigator.

•History of a hypersensitivity or allergies to Ramelteon or melatonin.

•History of contraindications as noted in the Ramelteon label

•History of significant stroke or vascular dementia.

•History of severe renal dysfunction or disease.

•History of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study drug. (This criterion does not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.)

•Any clinically significant movement disorder including but not limited to: akinesia, periodic limb movement disorder, restless leg syndrome, epilepsy, uncontrolled Parkinson's disease, or severe benign prostatic hyperplasia, cardiac asthma, chronic obstructive pulmonary disease.

•Rapid eye movement behavior disorder or sleep apnea.

•Any pain syndrome affecting sleep.

•Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

-Fluvoxamine

-Melatonin

-Rifampicin

Endpoints (9)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Behavior / neuropsychiatric

Fluid / digital biomarkers

Other (unclassified)

Behavior / neuropsychiatric

7 endpoints

Primary/protocol endpoint

Mean Nighttime Total Sleep Time as determined by actigraphy.

Time frame:Week 1

time to event, event

Secondary/protocol endpoint

Change from Baseline in Nighttime Total Sleep Time