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

Sponsor

Takeda (Industry)

Overall Status

Completed

CT.gov ID

NCT00325728

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy of ramelteon, once daily (QD), in subjects with mild to moderate Alzheimer's Disease and sleep disturbance

Condition or Disease	Intervention/Treatment	Phase
Chronic Insomnia	Drug: Ramelteon Drug: Placebo	Phase 2

Detailed Description

Epidemiological data for 2005 show that an estimated 4.2 million people in the US suffer from Alzheimer's disease, often necessitating caregiver assistance, which can in many cases progress to institutionalization. Subjects with Alzheimer's disease dementia frequently experience disturbed sleep patterns characterized by insufficient nocturnal sleep and excessive daytime napping, which has been associated with both cognitive and behavioral pathology such as impaired daytime functioning, agitation, and nocturnal wandering.

Although the causality of sleep disturbances in Alzheimer's disease remains unclear; some research suggests that the fragmented sleep and associated behavioral disturbances could be related to the degeneration of the serotonergic and noradrenergic innervation of suprachiasmatic nucleus andsubsequent disruption in melatonin secretion patterns. Additionally, research suggests that melatonin levels are decreased in patients with Alzheimer's disease

In the United States, ramelteon is marketed for the treatment of insomnia characterized by difficulty with sleep onset and is under global development for the treatment of transient, chronic insomnia and circadian rhythm sleep disorders. It is believed that ramelteon works by binding melatonin to MT1/MT2 receptors in the suprachiasmatic nucleus which inhibits firing of specific neurons, which is thought to attenuate the alerting signal and allows the homeostatic mechanism to express itself and promote sleep.

Study participation is anticipated to be about 11 weeks (approximately 3 months).

Study Design

Study Type:

Interventional

Actual Enrollment :

74 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 21, 2006

Actual Primary Completion Date :

Aug 1, 2007

Actual Study Completion Date :

Aug 20, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ramelteon 8 mg QD	Drug: Ramelteon Ramelteon 8mg, tablets, orally, once nightly for up to 8 weeks. Other Names: TAK-375 Rozerem
Placebo Comparator: Placebo	Drug: Placebo Ramelteon placebo matching tablets, orally, once nightly for up to 8 weeks.

Arm

Intervention/Treatment

Experimental: Ramelteon 8 mg QD

Drug: Ramelteon

Ramelteon 8mg, tablets, orally, once nightly for up to 8 weeks.

Other Names:

TAK-375

Rozerem

Placebo Comparator: Placebo

Drug: Placebo

Ramelteon placebo matching tablets, orally, once nightly for up to 8 weeks.

Outcome Measures

Primary Outcome Measures

Mean Nighttime Total Sleep Time as determined by actigraphy. [Week 1]

Secondary Outcome Measures

Change from Baseline in Nighttime Total Sleep Time [Weeks 2, 4, 6, and 8 or Final Visit]
Change from Baseline in Nighttime Wake After Sleep Onset per Actigraphy [Weeks 2, 4, 6, and 8 or Final Visit]
Change from Baseline in Nighttime Number Of Awakenings per Actigraphy [Weeks 2, 4, 6, and 8 or Final Visit]
Change from Baseline in Daytime Total Sleep Time [Weeks 2, 4, 6, and 8 or Final Visit]
Change from Baseline in the ratio of Daytime Total Sleep Time to Nighttime Total Sleep Time. [Weeks 2, 4, 6, and 8 or Final Visit]
Change from Baseline in Sleep Efficiency. [Weeks 2, 4, 6, and 8 or Final Visit]
Percentage of subjects who experience Increase in Nighttime Total Sleep Time of 30 minutes. [Weeks 2, 4, 6, and 8 or Final Visit]
Number of Daytime Naps. [Weeks 2, 4, 6, and 8 or Final Visit]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country
1	Alabaster	Alabama	United States
2	Huntsville	Alabama	United States
3	Phoenix	Arizona	United States
4	Sun City	Arizona	United States
5	Tucson	Arizona	United States
6	Costa Mesa	California	United States
7	Fresno	California	United States
8	Irvine	California	United States
9	Los Angeles	California	United States
10	National City	California	United States
11	Oxnard	California	United States
12	San Diego	California	United States
13	San Francisco	California	United States
14	Darien	Connecticut	United States
15	Waterbury	Connecticut	United States
16	Boynton Beach	Florida	United States
17	Bradenton	Florida	United States
18	Brooksville	Florida	United States
19	Deerfield Beach	Florida	United States
20	Fort Myers	Florida	United States
21	Hallandale Beach	Florida	United States
22	Hialeah	Florida	United States
23	Hollywood	Florida	United States
24	Largo	Florida	United States
25	Miami	Florida	United States
26	Naples	Florida	United States
27	Orange City	Florida	United States
28	Pompano Beach	Florida	United States
29	Port Charlotte	Florida	United States
30	Sarasota	Florida	United States
31	Sunrise	Florida	United States
32	Tampa	Florida	United States
33	West Palm Beach	Florida	United States
34	Atlanta	Georgia	United States
35	Savannah	Georgia	United States
36	Honolulu	Hawaii	United States
37	Chicago	Illinois	United States
38	Indianapolis	Indiana	United States
39	Lexington	Kentucky	United States
40	Boston	Massachusetts	United States
41	West Yarmouth	Massachusetts	United States
42	Grand Rapids	Michigan	United States
43	Saint Louis	Missouri	United States
44	Las Vegas	Nevada	United States
45	Dover	New Hampshire	United States
46	Manchester Township	New Jersey	United States
47	Piscataway	New Jersey	United States
48	Princeton	New Jersey	United States
49	Stratford	New Jersey	United States
50	Toms River	New Jersey	United States
51	Albuquerque	New Mexico	United States
52	Brooklyn	New York	United States
53	New Hyde Park	New York	United States
54	New York	New York	United States
55	Cincinnati	Ohio	United States
56	Columbus	Ohio	United States
57	Oklahoma City	Oklahoma	United States
58	Eugene	Oregon	United States
59	Havertown	Pennsylvania	United States
60	Jenkintown	Pennsylvania	United States
61	Moon	Pennsylvania	United States
62	Philadelphia	Pennsylvania	United States
63	Beaufort	South Carolina	United States
64	Greer	South Carolina	United States
65	North Charleston	South Carolina	United States
66	Bellaire	Texas	United States
67	Houston	Texas	United States
68	San Antonio	Texas	United States
69	Wichita Falls	Texas	United States
70	Bennington	Vermont	United States
71	Burlington	Vermont	United States
72	Middleton	Wisconsin	United States