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

Phase 4

Completed

• Conditions: Major Depressive Disorder; Insomnia
• Interventions: Drug: Ramelteon

• Registration Number: NCT02669082
• Lead Sponsor: Takeda

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.

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 Timeline

• Study First Submitted: 2016-01-27
• Study First Submitted QC: 2016-01-27
• Study First Posted: 2016-01-29
• Study Start: 2017-05-09
• Primary Completion: 2018-01-31
• Study Completion: 2018-01-31
• Results First Submitted: 2019-01-30
• Status Verified: 2019-05
• Results First Submitted QC: 2019-05-17
• Last Update Submitted: 2019-05-17
• Results First Posted: 2019-07-22
• Last Update Posted: 2019-07-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ramelteon 8 mg	Ramelteon	Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.
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.
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.
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.
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.
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.
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.

Trial Locations

Locations (7)

Sangenjaya Neurology and Psychosomatic Clinic; 🇯🇵 Setagaya, Tokyo, Japan

Himorogi Kokorono Clinic; 🇯🇵 Shinjuku, Tokyo, Japan

Ishikawa Mental Clinic; 🇯🇵 Sapporo, Hokkaido, Japan

You Ariyoshi Sleep Clinic; 🇯🇵 Kitakyushu, Fukuoka, Japan

Senzoku Psychosomatic Clinic; 🇯🇵 Meguro, Tokyo, Japan

Minami 1jo Mental Clinic; 🇯🇵 Sapporo, Hokkaido, Japan

Seiwa Hospital; 🇯🇵 Shinjuku, Tokyo, Japan