Insomnia, Major Depressive Disorder
Conditions
Keywords
Drug Therapy
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.
Interventions
DRUGRamelteon
Ramelteon tablets
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 64 Years
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 for11: 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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 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 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 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. |
Countries
Japan
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 details
Participants with a diagnosis of Major Depressive Disorder (MDD) with Insomnia were enrolled in 1 treatment arm: Ramelteon 8 mg.
Participants by arm
| Arm | Count |
|---|---|
| Ramelteon 8 mg Ramelteon 8 mg, tablet, orally, once daily at bedtime for 8 weeks. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Ramelteon 8 mg | — |
|---|---|---|
| Age, Continuous | 36.9 years STANDARD_DEVIATION 8.04 | — |
| Alcohol Consumption Per Week 0 day | 13 Participants | — |
| Alcohol Consumption Per Week 1 to 2 days | 8 Participants | — |
| Alcohol Consumption Per Week 3 to 5 days | 3 Participants | — |
| Alcohol Consumption Per Week 6 to 7 days | 2 Participants | — |
| Body Mass Index (BMI) | 24.94 kg/m^2 STANDARD_DEVIATION 3.888 | — |
| Daytime Activity Level by Actigraphy | 5815.17 steps STANDARD_DEVIATION 2826.252 | — |
| Duration of Depression | 3.622 years STANDARD_DEVIATION 4.5821 | — |
| Duration of Insomnia | 4.586 years STANDARD_DEVIATION 5.3492 | — |
| Height | 168.7 cm STANDARD_DEVIATION 8.53 | — |
| Nocturnal Wake Time by Actigraphy | 95.37 minutes STANDARD_DEVIATION 57.572 | — |
| Number of Nocturnal Awakenings by Actigraphy | 6.05 nocturnal awakenings STANDARD_DEVIATION 2.623 | — |
| Number of Nocturnal Awakenings by Sleep Diary | 1.87 nocturnal awakenings STANDARD_DEVIATION 1.079 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Japan | 26 Participants | — |
| Sex: Female, Male Female | 7 Participants | — |
| Sex: Female, Male Male | 19 Participants | — |
| Sleep Efficiency by Actigraphy | 67.039 percentage of sleep STANDARD_DEVIATION 12.0067 | — |
| Sleep Latency by Actigraphy | 44.81 minutes STANDARD_DEVIATION 20.29 | — |
| Sleep Latency by Sleep Diary | 51.21 minutes STANDARD_DEVIATION 51.957 | — |
| Smoking Classification Less than 20 Cigarettes per day | 11 Participants | — |
| Smoking Classification Non-smoking | 15 Participants | — |
| Total Nocturnal Sleep Time by Actigraphy | 314.89 minutes STANDARD_DEVIATION 74.285 | — |
| Total Nocturnal Sleep Time by Sleep Diary | 407.98 minutes STANDARD_DEVIATION 72.153 | — |
| Weight | 71.08 kg STANDARD_DEVIATION 12.548 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 26 |
| other Total, other adverse events | 9 / 26 |
| serious Total, serious adverse events | 0 / 26 |
Outcome results
Primary
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.
Time frame: Baseline and the end of the Treatment Period (up to Week 8)
Population: Full Analysis Set (FAS) was defined as all participants given at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg | Change From Baseline in Actigraphy-Measured Sleep Latency at the End of the Treatment Period | -6.81 minutes | Standard Deviation 32.498 |
Comparison: Data at Baseline compared to the data at the end of the Treatment Period.p-value: 0.2955t-test, 2 sided
Secondary
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.
Time frame: Baseline and the end of the Treatment Period (up to Week 8)
Population: FAS was defined as all participants given at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg | Change From Baseline in Actigraphy-Measured Daytime Activity Level, as Evaluated by the Number of Footsteps, at the End of the Treatment Period | 111.11 steps | Standard Deviation 2418.187 |
Comparison: Data at Baseline compared to the data at the end of the Treatment Period.p-value: 0.8166t-test, 2 sided
Secondary
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.
Time frame: Baseline and the end of the Treatment Period (up to Week 8)
Population: FAS was defined as all participants given at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg | Change From Baseline in Actigraphy-Measured Nocturnal Wake Time at the End of the Treatment Period | 10.07 minutes | Standard Deviation 38.739 |
Comparison: Data at Baseline compared to the data at the end of the Treatment Period.p-value: 0.1969t-test, 2 sided
Secondary
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.
Time frame: Baseline and the end of the Treatment Period (up to Week 8)
Population: FAS was defined as all participants given at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg | Change From Baseline in Actigraphy-Measured Number of Nocturnal Awakenings at the End of the Treatment Period | 0.53 nocturnal awakenings | Standard Deviation 1.338 |
Comparison: Data at Baseline compared to the data at the end of the Treatment Period.p-value: 0.0534t-test, 2 sided
Secondary
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.
Time frame: Baseline and the end of the Treatment Period (up to Week 8)
Population: FAS was defined as all participants given at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg | Change From Baseline in Actigraphy-Measured Sleep Efficiency at the End of the Treatment Period | 1.831 percentage of sleep | Standard Deviation 11.2028 |
Comparison: Data at Baseline compared to the data at the end of the Treatment Period.p-value: 0.4125t-test, 2 sided
Secondary
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.
Time frame: Baseline and the end of the Treatment Period (up to Week 8)
Population: FAS was defined as all participants given at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg | Change From Baseline in Actigraphy-Measured Total Nocturnal Sleep Time at the End of the Treatment Period | 24.20 minutes | Standard Deviation 87.47 |
Comparison: Data at Baseline compared to the data at the end of the Treatment Period.p-value: 0.1706t-test, 2 sided
Secondary
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.
Time frame: Baseline and the end of the Treatment Period (up to Week 8)
Population: FAS was defined as all participants given at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg | Change From Baseline in Diary-Measured Number of Nocturnal Awakenings at the End of the Treatment Period | -0.44 nocturnal awakenings | Standard Deviation 1.046 |
Comparison: Data at Baseline compared to the data at the end of the Treatment Period.p-value: 0.042t-test, 2 sided
Secondary
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.
Time frame: Baseline and the end of the Treatment Period (up to Week 8)
Population: FAS was defined as all participants given at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg | Change From Baseline in Diary-Measured Sleep Latency at the End of the Treatment Period | -11.51 minutes | Standard Deviation 38.087 |
Comparison: Data at Baseline compared to the data at the end of the Treatment Period.p-value: 0.1358t-test, 2 sided
Secondary
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.
Time frame: Baseline and the end of the Treatment Period (up to Week 8)
Population: FAS was defined as all participants given at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg | Change From Baseline in Diary-Measured Total Nocturnal Sleep Time at the End of the Treatment Period | 41.17 minutes | Standard Deviation 85.969 |
Comparison: Data at Baseline compared to the data at the end of the Treatment Period.p-value: 0.022t-test, 2 sided