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

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.

Study Overview

• Status: Completed
• Conditions: Insomnia; Major Depressive Disorder
• Intervention / Treatment: Drug: Ramelteon

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 Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan
      • YOU ARIYOSHI Sleep Clinic
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Ishikawa Mental Clinic
    • Sapporo, Hokkaido, Japan
      • Minami 1jo Mental Clinic
  • Tokyo
    • Meguro, Tokyo, Japan
      • Senzoku Psychosomatic Clinic
    • Setagaya, Tokyo, Japan
      • Sangenjaya Neurology and Psychosomatic Clinic
    • Shinjuku, Tokyo, Japan
      • Himorogi Kokorono Clinic
    • Shinjuku, Tokyo, Japan
      • Seiwa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Actigraphy-Measured Sleep Latency at the End of the Treatment Period	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.	Baseline and the end of the Treatment Period (up to Week 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Diary-Measured Sleep Latency at the End of the Treatment Period	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.	Baseline and the end of the Treatment Period (up to Week 8)
Change From Baseline in Actigraphy-Measured Total Nocturnal Sleep Time at the End of the Treatment Period	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.	Baseline and the end of the Treatment Period (up to Week 8)
Change From Baseline in Actigraphy-Measured Nocturnal Wake Time at the End of the Treatment Period	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.	Baseline and the end of the Treatment Period (up to Week 8)
Change From Baseline in Actigraphy-Measured Number of Nocturnal Awakenings at the End of the Treatment Period	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.	Baseline and the end of the Treatment Period (up to Week 8)
Change From Baseline in Actigraphy-Measured Sleep Efficiency at the End of the Treatment Period	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.	Baseline and the end of the Treatment Period (up to Week 8)
Change From Baseline in Diary-Measured Total Nocturnal Sleep Time at the End of the Treatment Period	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.	Baseline and the end of the Treatment Period (up to Week 8)
Change From Baseline in Diary-Measured Number of Nocturnal Awakenings at the End of the Treatment Period	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.	Baseline and the end of the Treatment Period (up to Week 8)
Change From Baseline in Actigraphy-Measured Daytime Activity Level, as Evaluated by the Number of Footsteps, at the End of the Treatment Period	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.	Baseline and the end of the Treatment Period (up to Week 8)

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2017
• Primary Completion (Actual): January 31, 2018
• Study Completion (Actual): January 31, 2018

Study Registration Dates

• First Submitted: January 27, 2016
• First Submitted That Met QC Criteria: January 27, 2016
• First Posted (Estimate): January 29, 2016

Study Record Updates

• Last Update Posted (Actual): July 22, 2019
• Last Update Submitted That Met QC Criteria: May 17, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Nervous System Diseases; Mood Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Depression; Depressive Disorder; Sleep Initiation and Maintenance Disorders; Depressive Disorder, Major
• Other Study ID Numbers: Ramelteon-4002; JapicCTI-163143 (Registry Identifier: JapicCTI); U1111-1177-4116 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No