The Exploratory Study to Investigate the Effect of Ramelteon for Insomnia Patients With Major Depressive Disorder by Using Actigraphy

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02669082
• Collaborator: (none)
• Enrollment: 26
• Locations: 7
• Arm: 1
• Actual Duration (Months): 8.8
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate exploratorily the effect of ramelteon 8 mg once daily for 8 weeks in the treatment of insomnia patients with depression by using actigraphy.

Condition or Disease	Intervention/Treatment	Phase
Insomnia; Major Depressive Disorder	Drug: Ramelteon	Phase 4

Detailed Description

The drug being tested in this study is called ramelteon. Ramelteon is being tested to treat people who have insomnia with depression. This study will look at sleep activity of participants who take ramelteon.

The study will enroll approximately 30 patients. Participants will be administered:

• Ramelteon 8 mg

Participants will be asked to take 1 tablet orally at bedtime. This multi-center study will be conducted in Japan. The overall period to participate in this study is 9 weeks (Run-in period for 1 week and treatment period for 8 weeks). Participants will make multiple visits to clinic including the final visit 8 weeks after the start of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Exploratory Study to Investigate the Effect of Ramelteon for Insomnia Patients With Major Depressive Disorder by Using Actigraphy
• Actual Study Start Date: May 9, 2017
• Actual Primary Completion Date: Jan 31, 2018
• Actual Study Completion Date: Jan 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ramelteon 8 mg Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.	Drug: Ramelteon; Ramelteon tablets; Other Names: Rozerem TAK-375

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Actigraphy-Measured Sleep Latency at the End of the Treatment Period [Baseline and the end of the Treatment Period (up to Week 8)]

   Sleep latency was defined as time period measured from "lights out," or bedtime, to the beginning of sleep. Sleep latency was assessed by actigraphy, a non-intrusive tool that measures an individual's movement during sleep. Mean value from the past 7 days was evaluated. A negative change from Baseline indicates improvement.

Secondary Outcome Measures

1. Change From Baseline in Diary-Measured Sleep Latency at the End of the Treatment Period [Baseline and the end of the Treatment Period (up to Week 8)]

   Sleep latency was defined as time period measured from "lights out," or bedtime, to the beginning of sleep. Sleep latency was recorded by the participant in a diary. Mean value from the past 7 days at each timepoint was evaluated. A negative change from Baseline indicates improvement.

2. Change From Baseline in Actigraphy-Measured Total Nocturnal Sleep Time at the End of the Treatment Period [Baseline and the end of the Treatment Period (up to Week 8)]

   Total nocturnal sleep time was assessed by actigraphy, a non-intrusive tool that measures an individual's movement during sleep. Total nocturnal sleep time by actigraphy was total time in bed from which sleep latency, nocturnal wake time, and the time from waking up to leaving the bed were subtracted. Mean value from the past 7 days at each timepoint was evaluated. A positive change from Baseline indicates improvement.

3. Change From Baseline in Actigraphy-Measured Nocturnal Wake Time at the End of the Treatment Period [Baseline and the end of the Treatment Period (up to Week 8)]

   Nocturnal wake time is the total time that is scored between nocturnal sleep onset and final wake-up. Nocturnal wake time was assessed by actigraphy, a non-intrusive tool that measures an individual's movement during sleep. Mean value from the past 7 days at each timepoint was evaluated. A positive change from Baseline indicates a worsening.

4. Change From Baseline in Actigraphy-Measured Number of Nocturnal Awakenings at the End of the Treatment Period [Baseline and the end of the Treatment Period (up to Week 8)]

   The number of nocturnal awakenings were assessed by actigraphy which is a non-intrusive tool that measures an individual's movement during sleep. Mean value from the past 7 days at each time point was evaluated. A positive change from Baseline indicates a worsening.

5. Change From Baseline in Actigraphy-Measured Sleep Efficiency at the End of the Treatment Period [Baseline and the end of the Treatment Period (up to Week 8)]

   Sleep efficiency was defined as percentage of sleep in the period potentially filled by sleep-ratio of total sleep time to time in bed calculated as [(Total sleep time/total time in bed) * 100]. Sleep efficiency was assessed by actigraphy, a non-intrusive tool that measures an individual's movement during sleep. Mean value from the past 7 days at each timepoint was evaluated. A positive change from Baseline indicates improvement.

6. Change From Baseline in Diary-Measured Total Nocturnal Sleep Time at the End of the Treatment Period [Baseline and the end of the Treatment Period (up to Week 8)]

   Total nocturnal sleep time by diary was calculated as total time in bed (awaking hour - bedtime hour) from which sleep latency was subtracted. Mean value from the past 7 days at each timepoint was evaluated. A positive change from Baseline indicates improvement.

7. Change From Baseline in Diary-Measured Number of Nocturnal Awakenings at the End of the Treatment Period [Baseline and the end of the Treatment Period (up to Week 8)]

   The number of nocturnal awakenings were recorded by the participant in a diary. Mean value from the past 7 days at each timepoint was evaluated. A negative change from Baseline indicates improvement.

8. Change From Baseline in Actigraphy-Measured Daytime Activity Level, as Evaluated by the Number of Footsteps, at the End of the Treatment Period [Baseline and the end of the Treatment Period (up to Week 8)]

   Daytime activity level, as evaluated by the number of footsteps, were assessed by actigraphy, a non-intrusive tool that measures an individual's movement. Mean value from the past 7 days at each timepoint was evaluated. A positive change from Baseline indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Has difficulty in initiating sleep at least 3 days per week for at least 4 weeks at the time of informed consent.

2. Has Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5)-defined depression.

3. Man or woman between 20 and 64 years of age, inclusive, at the time of informed consent.

4. Outpatient.

5. Meets either of the following criteria based on the 17-item Hamilton Rating Scale for Depression (HAM-D17) both at the start of the run-in period and the start of the study treatment period: has a score of 2 for "6: Insomnia Early", or has a score of 1 for "6: Insomnia Early" AND a score of at least 3 in total for "7: Insomnia Middle" and "8: Insomnia Late".

6. Has a total HAM-D17 score of 16 or under both at the start of the run-in period and the start of the study treatment period.

7. Under treatment of the same antidepressant agents on a stable dose for at least 4 weeks before the start of the run-in period.

8. Goes to bed routinely in a daily life (time for bed between 21.00 p.m. and 1.00 a.m. at least 4 days per week).

9. Actigraphy shows at least 3 days with sleep latency 30 minutes or longer AND total nocturnal sleep time 6.5 hours or shorter on the same day during the run-in period.

10. In the opinion of the principal investigator or investigator, is capable of understanding the contents of the study and complying with study requirements.

11. Is capable of signing and dating the informed consent form in person before any study procedures.

Exclusion Criteria:

1. Has a history of hypersensitivity to ramelteon and melatonin.

2. Has severe liver disorder.

3. Took ramelteon within 4 weeks before the informed consent.

4. Using any insomnia medications (including investigational drugs and unapproved drugs) for 2 weeks before the treatment period.

5. Shift worker or night worker.

6. Has complications of psychiatric or neurological diseases that affect sleep state other than depression.

7. Has a HAM-D17 score of at least 1 for"11: Suicide" at the start of the run-in period or the start of the study treatment period, or any suicide attempts within 24 weeks before or during the run-in period.

8. Pregnant woman, nursing mother, or woman who plans to become pregnant or donate eggs before the informed consent, during the study period or within 4 weeks after the end of the study.

9. Is participating in any other investigational or post-marketing clinical trial/study.

10. For other reason, judged not appropriate for participation in this study by the principal investigator or investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	You Ariyoshi Sleep Clinic	Kitakyushu	Fukuoka	Japan
2	Ishikawa Mental Clinic	Sapporo	Hokkaido	Japan
3	Minami 1jo Mental Clinic	Sapporo	Hokkaido	Japan
4	Senzoku Psychosomatic Clinic	Meguro	Tokyo	Japan
5	Sangenjaya Neurology and Psychosomatic Clinic	Setagaya	Tokyo	Japan
6	Himorogi Kokorono Clinic	Shinjuku	Tokyo	Japan
7	Seiwa Hospital	Shinjuku	Tokyo	Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Statistical Analysis Plan - Feb 26, 2018
• Study Protocol - Jul 31, 2017

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02669082
• Other Study ID Numbers: Ramelteon-4002; JapicCTI-163143; U1111-1177-4116
• First Posted: Jan 29, 2016
• Last Update Posted: Jul 22, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug Therapy
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 7 investigative sites in Japan from 09 May 2017 to 31 January 2018.
Pre-assignment Detail	Participants with a diagnosis of Major Depressive Disorder (MDD) with Insomnia were enrolled in 1 treatment arm: Ramelteon 8 mg.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Period Title: Overall Study
STARTED	26
COMPLETED	25
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Overall Participants	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.9 (8.04)
Sex: Female, Male (Count of Participants)
Female	7 26.9%
Male	19 73.1%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
Japan	26 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	168.7 (8.53)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	71.08 (12.548)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.94 (3.888)
Smoking Classification (Count of Participants)
Non-smoking	15 57.7%
Less than 20 Cigarettes per day	11 42.3%
Alcohol Consumption Per Week (Count of Participants)
0 day	13 50%
1 to 2 days	8 30.8%
3 to 5 days	3 11.5%
6 to 7 days	2 7.7%
Duration of Insomnia (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.586 (5.3492)
Duration of Depression (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.622 (4.5821)
Sleep Latency by Actigraphy (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]	44.81 (20.290)
Sleep Latency by Sleep Diary (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]	51.21 (51.957)
Total Nocturnal Sleep Time by Actigraphy (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]	314.89 (74.285)
Total Nocturnal Sleep Time by Sleep Diary (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]	407.98 (72.153)
Number of Nocturnal Awakenings by Actigraphy (nocturnal awakenings) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nocturnal awakenings]	6.05 (2.623)
Number of Nocturnal Awakenings by Sleep Diary (nocturnal awakenings) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nocturnal awakenings]	1.87 (1.079)
Nocturnal Wake Time by Actigraphy (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]	95.37 (57.572)
Sleep Efficiency by Actigraphy (percentage of sleep) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of sleep]	67.039 (12.0067)
Daytime Activity Level by Actigraphy (steps) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [steps]	5815.17 (2826.252)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Actigraphy-Measured Sleep Latency at the End of the Treatment Period
Description	Sleep latency was defined as time period measured from "lights out," or bedtime, to the beginning of sleep. Sleep latency was assessed by actigraphy, a non-intrusive tool that measures an individual's movement during sleep. Mean value from the past 7 days was evaluated. A negative change from Baseline indicates improvement.
Time Frame	Baseline and the end of the Treatment Period (up to Week 8)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) was defined as all participants given at least 1 dose of study drug.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Measure Participants	26
Mean (Standard Deviation) [minutes]	-6.81 (32.498)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg
	Comments	Data at Baseline compared to the data at the end of the Treatment Period.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2955
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Change From Baseline in Diary-Measured Sleep Latency at the End of the Treatment Period
Description	Sleep latency was defined as time period measured from "lights out," or bedtime, to the beginning of sleep. Sleep latency was recorded by the participant in a diary. Mean value from the past 7 days at each timepoint was evaluated. A negative change from Baseline indicates improvement.
Time Frame	Baseline and the end of the Treatment Period (up to Week 8)

Outcome Measure Data

Analysis Population Description

FAS was defined as all participants given at least 1 dose of study drug.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Measure Participants	26
Mean (Standard Deviation) [minutes]	-11.51 (38.087)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg
	Comments	Data at Baseline compared to the data at the end of the Treatment Period.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1358
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Change From Baseline in Actigraphy-Measured Total Nocturnal Sleep Time at the End of the Treatment Period
Description	Total nocturnal sleep time was assessed by actigraphy, a non-intrusive tool that measures an individual's movement during sleep. Total nocturnal sleep time by actigraphy was total time in bed from which sleep latency, nocturnal wake time, and the time from waking up to leaving the bed were subtracted. Mean value from the past 7 days at each timepoint was evaluated. A positive change from Baseline indicates improvement.
Time Frame	Baseline and the end of the Treatment Period (up to Week 8)

Outcome Measure Data

Analysis Population Description

FAS was defined as all participants given at least 1 dose of study drug.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Measure Participants	26
Mean (Standard Deviation) [minutes]	24.20 (87.470)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg
	Comments	Data at Baseline compared to the data at the end of the Treatment Period.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1706
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Change From Baseline in Actigraphy-Measured Nocturnal Wake Time at the End of the Treatment Period
Description	Nocturnal wake time is the total time that is scored between nocturnal sleep onset and final wake-up. Nocturnal wake time was assessed by actigraphy, a non-intrusive tool that measures an individual's movement during sleep. Mean value from the past 7 days at each timepoint was evaluated. A positive change from Baseline indicates a worsening.
Time Frame	Baseline and the end of the Treatment Period (up to Week 8)

Outcome Measure Data

Analysis Population Description

FAS was defined as all participants given at least 1 dose of study drug.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Measure Participants	26
Mean (Standard Deviation) [minutes]	10.07 (38.739)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg
	Comments	Data at Baseline compared to the data at the end of the Treatment Period.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1969
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Change From Baseline in Actigraphy-Measured Number of Nocturnal Awakenings at the End of the Treatment Period
Description	The number of nocturnal awakenings were assessed by actigraphy which is a non-intrusive tool that measures an individual's movement during sleep. Mean value from the past 7 days at each time point was evaluated. A positive change from Baseline indicates a worsening.
Time Frame	Baseline and the end of the Treatment Period (up to Week 8)

Outcome Measure Data

Analysis Population Description

FAS was defined as all participants given at least 1 dose of study drug.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Measure Participants	26
Mean (Standard Deviation) [nocturnal awakenings]	0.53 (1.338)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg
	Comments	Data at Baseline compared to the data at the end of the Treatment Period.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0534
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Change From Baseline in Actigraphy-Measured Sleep Efficiency at the End of the Treatment Period
Description	Sleep efficiency was defined as percentage of sleep in the period potentially filled by sleep-ratio of total sleep time to time in bed calculated as [(Total sleep time/total time in bed) * 100]. Sleep efficiency was assessed by actigraphy, a non-intrusive tool that measures an individual's movement during sleep. Mean value from the past 7 days at each timepoint was evaluated. A positive change from Baseline indicates improvement.
Time Frame	Baseline and the end of the Treatment Period (up to Week 8)

Outcome Measure Data

Analysis Population Description

FAS was defined as all participants given at least 1 dose of study drug.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Measure Participants	26
Mean (Standard Deviation) [percentage of sleep]	1.831 (11.2028)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg
	Comments	Data at Baseline compared to the data at the end of the Treatment Period.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4125
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Change From Baseline in Diary-Measured Total Nocturnal Sleep Time at the End of the Treatment Period
Description	Total nocturnal sleep time by diary was calculated as total time in bed (awaking hour - bedtime hour) from which sleep latency was subtracted. Mean value from the past 7 days at each timepoint was evaluated. A positive change from Baseline indicates improvement.
Time Frame	Baseline and the end of the Treatment Period (up to Week 8)

Outcome Measure Data

Analysis Population Description

FAS was defined as all participants given at least 1 dose of study drug.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Measure Participants	26
Mean (Standard Deviation) [minutes]	41.17 (85.969)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg
	Comments	Data at Baseline compared to the data at the end of the Treatment Period.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0220
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Change From Baseline in Diary-Measured Number of Nocturnal Awakenings at the End of the Treatment Period
Description	The number of nocturnal awakenings were recorded by the participant in a diary. Mean value from the past 7 days at each timepoint was evaluated. A negative change from Baseline indicates improvement.
Time Frame	Baseline and the end of the Treatment Period (up to Week 8)

Outcome Measure Data

Analysis Population Description

FAS was defined as all participants given at least 1 dose of study drug.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Measure Participants	26
Mean (Standard Deviation) [nocturnal awakenings]	-0.44 (1.046)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg
	Comments	Data at Baseline compared to the data at the end of the Treatment Period.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0420
	Comments
	Method	t-test, 2 sided
	Comments

9. Secondary Outcome

Title	Change From Baseline in Actigraphy-Measured Daytime Activity Level, as Evaluated by the Number of Footsteps, at the End of the Treatment Period
Description	Daytime activity level, as evaluated by the number of footsteps, were assessed by actigraphy, a non-intrusive tool that measures an individual's movement. Mean value from the past 7 days at each timepoint was evaluated. A positive change from Baseline indicates improvement.
Time Frame	Baseline and the end of the Treatment Period (up to Week 8)

Outcome Measure Data

Analysis Population Description

FAS was defined as all participants given at least 1 dose of study drug.

Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
Measure Participants	26
Mean (Standard Deviation) [steps]	111.11 (2418.187)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon 8 mg
	Comments	Data at Baseline compared to the data at the end of the Treatment Period.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8166
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Up to Week 8
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Ramelteon 8 mg
Arm/Group Description	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.
All Cause Mortality
	Ramelteon 8 mg
	Affected / at Risk (%)	# Events
Total	0/26 (0%)
Serious Adverse Events
	Ramelteon 8 mg
	Affected / at Risk (%)	# Events
Total	0/26 (0%)
Other (Not Including Serious) Adverse Events
	Ramelteon 8 mg
	Affected / at Risk (%)	# Events
Total	9/26 (34.6%)
Infections and infestations
Viral upper respiratory tract infections	5/26 (19.2%)
Nervous system disorders
Somnolence	4/26 (15.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.