Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia

Sponsor

Takeda (Industry)

Overall Status

Completed

CT.gov ID

NCT00671255

Collaborator

(none)

829

Enrollment

115

Locations

Arms

Duration (Months)

7.2

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This purpose of this study is to evaluate the safety and effectiveness of Ramelteon, once daily (QD), in elderly participants with chronic insomnia.

Condition or Disease	Intervention/Treatment	Phase
Chronic Insomnia	Drug: Ramelteon Drug: Ramelteon Drug: Placebo	Phase 3

Detailed Description

Insomnia is characterized by a complaint of initiating and maintaining sleep or complaints of nonrestorative and non-refreshing sleep. Transient insomnia affects approximately one-third to one-half of the US population, based on the results of 2 surveys of representative samples of the adult US population conducted by the Gallup Organization in which respondents were asked if they had "ever had difficulty sleeping." Based on reports of "regular" or "frequent" sleep difficulty, results from the same studies suggest that approximately one-tenth of the US population experiences chronic insomnia. The ideal treatment for insomnia would reduce the latency to onset of sleep and increase total sleep time, without a negative impact on sleep architecture and without safety concerns or next-day effects.

Ramelteon is a selective melatonin-1 receptor agonist under development by Takeda Chemical Industries, Ltd., for the treatment of transient and chronic insomnia and for the treatment of Circadian Rhythm Sleep Disorders.

Ramelteon is the first candidate in a novel class of drugs based on this mechanism. Based on non-clinical and clinical studies completed to date, TAK-375 has the potential to offer unique advantages relative to approved hypnotics in terms of its pharmacological profile and its selectivity to the melatonin-1 receptor.

This study is designed to determine the safety and efficacy of 35-day treatment of chronic insomnia with ramelteon. Participation in this study is anticipated to be approximately 2 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

829 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

Official Title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Outpatient, Safety and Efficacy Study of TAK-375 in Elderly Subjects With Chronic Insomnia

Study Start Date :

Dec 1, 2002

Actual Primary Completion Date :

Jan 1, 2004

Actual Study Completion Date :

Jan 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ramelteon 4 mg QD	Drug: Ramelteon Ramelteon 4 mg, tablets, orally, once daily for up to 5 weeks. Other Names: Rozerem™ TAK-375
Experimental: Ramelteon 8 mg QD	Drug: Ramelteon Ramelteon 8 mg, tablets, orally, once daily for up to 5 weeks. Other Names: Rozerem™ TAK-375
Placebo Comparator: Placebo	Drug: Placebo Ramelteon placebo-matching, tablets, orally, each night for up to 35 consecutive days.

Arm

Intervention/Treatment

Experimental: Ramelteon 4 mg QD

Drug: Ramelteon

Ramelteon 4 mg, tablets, orally, once daily for up to 5 weeks.

Other Names:

Rozerem™

TAK-375

Experimental: Ramelteon 8 mg QD

Drug: Ramelteon

Ramelteon 8 mg, tablets, orally, once daily for up to 5 weeks.

Other Names:

Rozerem™

TAK-375

Placebo Comparator: Placebo

Drug: Placebo

Ramelteon placebo-matching, tablets, orally, each night for up to 35 consecutive days.

Outcome Measures

Primary Outcome Measures

Mean Subjective Sleep Latency per subject diary, from Nights 1 through 7 of double-blind Treatment [Weeks 1, 2, 3, 4 and 5 or Final Visit.]

Secondary Outcome Measures

Subjective Total Sleep Time. [Weeks 1, 2, 3, 4 and 5 or Final Visit.]
Subjective Number of Awakenings. [Weeks 1, 2, 3, 4 and 5 or Final Visit.]
Subjective Ease of Falling Back to Sleep after Awakening. [Weeks 1, 2, 3, 4 and 5 or Final Visit.]
Subjective Sleep Quality. [Weeks 1, 2, 3, 4 and 5 or Final Visit.]
Clinical Global Impression Change of Condition. [Weeks 1, 2, 3, 4 and 5 or Final Visit.]
Clinical Global Impression Severity of Illness. [Weeks 1, 2, 3, 4 and 5 or Final Visit.]
Clinical Global Impression Therapeutic Effect. [Weeks 1, 2, 3, 4 and 5 or Final Visit.]
Clinical Global Impression Side Effects. [Weeks 1, 2, 3, 4 and 5 or Final Visit.]
Average Subjective Sleep Latency over the week preceding the Day 15, Day 22, Day 29, and Day 36 Visits. [Weeks 2, 3, 4 and 5 or Final Visit.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Subject is a male or a post-menopausal female.
Primary insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised for at least 3 months and a history of daytime complaint(s) associated with disturbed sleep.
Subjective sleep latency greater than or equal to 45 minutes and a subjective total sleep time less than or equal to 6.5 hours per night for at least 3 nights during the week of the lead-in period.
Habitual bedtime is between 8:30 PM and 12:00 AM.
Body mass index between 18 and 34, inclusive.

Exclusion Criteria

Known hypersensitivity to ramelteon or related compounds, including melatonin.
Previously participated in a study involving ramelteon.
Participated in any other investigational study, and/or took any investigational drug within 30 days or five half-lives prior to the first day of single-blind study medication, whichever is longer.
Sleep schedule changes required by employment (eg, shift worker) within three months prior to the first day of single-blind study medication, or has flown across greater than three time zones within seven days prior to screening.
Participated in a weight loss program or substantially altered exercise routine within 30 days prior to the first day of single blind study medication.
Has ever had a history of seizures, sleep apnea, chronic obstructive pulmonary disease, restless leg syndrome, schizophrenia, bipolar disorder, mental retardation, or cognitive disorder.
History of psychiatric disorder within the past 12 months.
History of drug addiction or drug abuse within the past 12 months.
History of alcohol abuse within the past 12 months, as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised and/or regularly consumes 4 or more alcoholic drinks per day.
Current significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic or metabolic disease, unless currently controlled and stable with protocol-allowed medication.
Uses tobacco products during nightly awakenings.
Any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.
Positive hepatitis panel.
Any additional condition(s) that in the Investigator's opinion would:
affect sleep-wake function
prohibit the subject from completing the study
not be in the best interest of the subject.
Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication, including:
Anxiolytics
Hypnotics
Antidepressants
Anticonvulsants
Sedating H1 antihistamines
Systemic steroids
Respiratory stimulants
Decongestants
Over-the-counter and prescription stimulants
Over-the-counter and prescription diet aids
Central nervous system active drugs
Narcotic analgesics
All beta blockers
Melatonin
St. John's Wort
Kava-kava
Gingko biloba

Contacts and Locations

Locations

	City	State	Country
1	Columbiana	Alabama	United States
2	Mobile	Alabama	United States
3	Muscle Shoals	Alabama	United States
4	Tallahassee	Alabama	United States
5	Phoenix	Arizona	United States
6	Scottsdale	Arizona	United States
7	Tempe	Arizona	United States
8	Hot Springs	Arkansas	United States
9	Little Rock	Arkansas	United States
10	Anaheim	California	United States
11	Encinitas	California	United States
12	Irvine	California	United States
13	La Jolla	California	United States
14	La Mesa	California	United States
15	Los Angeles	California	United States
16	Murrieta	California	United States
17	Northridge	California	United States
18	Oakland	California	United States
19	Redlands	California	United States
20	Riverside	California	United States
21	Rosemead	California	United States
22	San Diego	California	United States
23	Spring Valley	California	United States
24	Vista	California	United States
25	Colorado Springs	Colorado	United States
26	Denver	Colorado	United States
27	Clearwater	Florida	United States
28	DeLand	Florida	United States
29	Hollywood	Florida	United States
30	Jacksonville	Florida	United States
31	Kissimmee	Florida	United States
32	Longwood	Florida	United States
33	Pembroke Pines	Florida	United States
34	Pinellas Park	Florida	United States
35	Safety Harbor	Florida	United States
36	St. Petersburg	Florida	United States
37	Tampa	Florida	United States
38	Vero Beach	Florida	United States
39	West Palm Beach	Florida	United States
40	Winter Park	Florida	United States
41	Atlanta	Georgia	United States
42	Blairsville	Georgia	United States
43	Macon	Georgia	United States
44	Chciago	Illinois	United States
45	Northfield	Illinois	United States
46	Evansville	Indiana	United States
47	Shawnee Mission	Kansas	United States
48	Wichita	Kansas	United States
49	Louisville	Kentucky	United States
50	Murray	Kentucky	United States
51	New Orleans	Louisiana	United States
52	Bethesda	Maryland	United States
53	Belmont	Massachusetts	United States
54	Brockton	Massachusetts	United States
55	Newton	Massachusetts	United States
56	Detroit	Michigan	United States
57	Hattiesburg	Mississippi	United States
58	Kansas City	Missouri	United States
59	St. Louis	Missouri	United States
60	Lincoln	Nebraska	United States
61	Las Vegas	Nevada	United States
62	Brick	New Jersey	United States
63	Edison	New Jersey	United States
64	Toms River	New Jersey	United States
65	Albuquerque	New Mexico	United States
66	Great Neck	New York	United States
67	Manlius	New York	United States
68	Mineola	New York	United States
69	Williamsville	New York	United States
70	Cary	North Carolina	United States
71	Greensboro	North Carolina	United States
72	Hickory	North Carolina	United States
73	Raleigh	North Carolina	United States
74	Salisbury	North Carolina	United States
75	Winston-Salem	North Carolina	United States
76	Beachwood	Ohio	United States
77	Canfield	Ohio	United States
78	Cincinnati	Ohio	United States
79	Toledo	Ohio	United States
80	Oklahoma City	Oklahoma	United States
81	Tulsa	Oklahoma	United States
82	Eugene	Oregon	United States
83	Portland	Oregon	United States
84	Jenkintown	Pennsylvania	United States
85	Reading	Pennsylvania	United States
86	Scotland	Pennsylvania	United States
87	Warwick	Rhode Island	United States
88	Anderson	South Carolina	United States
89	Greer	South Carolina	United States
90	Mt. Pleasant	South Carolina	United States
91	Fayetteville	Tennessee	United States
92	Johnson City	Tennessee	United States
93	Dallas	Texas	United States
94	Fort Worth	Texas	United States
95	Houston	Texas	United States
96	San Antonio	Texas	United States
97	Salt Lake City	Utah	United States
98	Norfolk	Virginia	United States
99	Bellevue	Washington	United States
100	Gig Harbor	Washington	United States
101	Madison	Wisconsin	United States
102	New Berlin	Wisconsin	United States
103	Calgary	Alberta	Canada
104	Edmonton	Alberta	Canada
105	Medicine Hat	Alberta	Canada
106	North Vancouver	British Columbia	Canada
107	Winnipeg	Manitoba	Canada
108	St. John's	Newfoundland and Labrador	Canada
109	Corunna	Ontario	Canada
110	London	Ontario	Canada
111	North Bay	Ontario	Canada
112	Sarnia	Ontario	Canada
113	Toronto	Ontario	Canada
114	Parkdale	Prince Edward Island	Canada
115	Montreal	Quebec	Canada