Clinical trial NCT00325728 (phase 2, status: completed)
Conditions: chronic insomnia
ICD codes: F51.01, F51.02, F51.03, F51.04, G47.00, G47.09, A81.83
Drugs: ramelteon, placebo
SMILES: CCC(=O)NCC[C@@H]1CCC2=C1C1=C(OCC1)C=C2, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        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