Insomnia
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to investigate the safety and efficacy of ramelteon (Rozerem) when used in the routine clinical setting in patients with sleep-onset difficulty associated with insomnia.
Detailed description
This is a drug use surveillance planned to examine the safety and efficacy of ramelteon tablets when used in the routine clinical setting in patients with sleep-onset difficulty associated with insomnia (planned sample size, 3000) The usual adult dosage is 8 mg of ramelteon administered orally once daily at bedtime.
Interventions
DRUGRamelteon
Ramelteon 8 mg tablets
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1\. Sleep-onset difficulty associated with insomnia
Exclusion criteria
1. Patients with previous history of hypersensitivity to an ingredient of Rozerem Tablets 2. Patients with severe liver dysfunction 3. Patients taking fluvoxamine maleate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting One or More Adverse Drug Reactions | Baseline up to 6 weeks | Adverse drug reactions are defined as adverse events (AE) which are in the investigator's opinion of causal relationship to the study treatment. AE are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug. |
| Number of Participants Reporting One or More Serious Adverse Drug Reactions | Baseline up to 6 weeks | Serious adverse drug reactions are defined as serious adverse events (SAE) which are in the investigator's opinion of causal relationship to the study treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Status: Sleep Onset Latency | Baseline and Week 4 | Sleep status was determined by measuring the sleep onset latency, defined as the length of time taken from lying down for the night until sleep onset. |
| Sleep Status: Total Sleep Time | Baseline and Week 4 | Sleep status was determined by measuring the total sleep time, defined as the amount of actual sleep time during a sleep episode. |
| Sleep Status: Number of Awakenings | Baseline and Week 4 | Sleep status of participants was assessed and summarized by calculating the number of times participants had awaken from the time of start of the investigation. |
| Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 | Week 4 | PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. 7 items on scale include sleep onset, sleep time, sleep quality, morning awakening, morning tiredness, daytime somnolence, and daytime physical condition/function. Participants provide their response on a PGI questionnaire. The results of survey using the PGI questionnaire was scored, summarized and assessed. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as much better or a little better were reported for sleep onset,time, quality; morning awakening, tiredness and daytime sleepiness, physical condition. |
Participant flow
Recruitment details
Participants took part in the study at 557 investigative site in Japan from 30 July 2010 to 30 April 2013.
Pre-assignment details
Participants with a historical diagnosis of insomnia who were facing difficulty in falling asleep in daily clinical practice were enrolled in single treatment group to receive ramelteon 8 milligram (mg).
Participants by arm
| Arm | Count |
|---|---|
| Ramelteon Ramelteon 8 mg, tablets, orally, once as daily clinical practice were observed for up to 4 weeks. A follow up of 2 weeks was carried out. | 3,223 |
| Total | 3,223 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | CRF Uncollected | 20 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Protocol Violation | 92 |
Baseline characteristics
| Characteristic | Ramelteon |
|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 18.9 |
| Age, Customized >=75 years | 1111 participants |
| Age, Customized Greater than or equal to (>=)65 years to <75 years | 733 participants |
| Age, Customized Less than (<) 65 years | 1379 participants |
| Breakdown of complications Diabetes mellitus | 419 participants |
| Breakdown of complications Dyslipidaemia | 694 participants |
| Breakdown of complications Heart or cerebrovascular disease | 393 participants |
| Breakdown of complications Hepatobiliary disorders | 133 participants |
| Breakdown of complications Hypertension | 1206 participants |
| Breakdown of complications Mental disease | 495 participants |
| Breakdown of complications Renal and urinary disorders | 158 participants |
| Degree of Sleep Disorder Mild | 1354 participants |
| Degree of Sleep Disorder Moderate | 1569 participants |
| Degree of Sleep Disorder Severe | 300 participants |
| Duration of Insomnia < 1 year | 1522 participants |
| Duration of Insomnia >=1 year to <3 years | 241 participants |
| Duration of Insomnia >=3 to < 5 years | 107 participants |
| Duration of Insomnia >=5 years | 135 participants |
| Duration of Insomnia Unknown | 1218 participants |
| Duration of Insomnia | 1.13 years STANDARD_DEVIATION 2.45 |
| Presence of Complications Had Complications | 2618 participants |
| Presence of Complications Had No Complications | 605 participants |
| Sex: Female, Male Female | 1935 Participants |
| Sex: Female, Male Male | 1288 Participants |
| Type of Sleep Disorder (Major Symptoms) Difficulty falling asleep | 1966 participants |
| Type of Sleep Disorder (Major Symptoms) Difficulty getting sound sleep | 302 participants |
| Type of Sleep Disorder (Major Symptoms) Difficulty staying asleep | 458 participants |
| Type of Sleep Disorder (Major Symptoms) Early morning awakening | 50 participants |
| Type of Sleep Disorder (Major Symptoms) Unknown | 447 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 37 / 3,223 |
| serious Total, serious adverse events | 1 / 3,223 |
Outcome results
Primary
Number of Participants Reporting One or More Adverse Drug Reactions
Adverse drug reactions are defined as adverse events (AE) which are in the investigator's opinion of causal relationship to the study treatment. AE are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.
Time frame: Baseline up to 6 weeks
Population: Safety analysis set was defined as participants who were enrolled and completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramelteon | Number of Participants Reporting One or More Adverse Drug Reactions | 109 participants |
Primary
Number of Participants Reporting One or More Serious Adverse Drug Reactions
Serious adverse drug reactions are defined as serious adverse events (SAE) which are in the investigator's opinion of causal relationship to the study treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Baseline up to 6 weeks
Population: SAS was defined as participants who were enrolled and completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramelteon | Number of Participants Reporting One or More Serious Adverse Drug Reactions | 1 participants |
Secondary
Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4
PGI is a participant rated instrument to measure participant's change in overall status on a 7-point scale. 7 items on scale include sleep onset, sleep time, sleep quality, morning awakening, morning tiredness, daytime somnolence, and daytime physical condition/function. Participants provide their response on a PGI questionnaire. The results of survey using the PGI questionnaire was scored, summarized and assessed. Total score range from 1 (very much improved) to 7 (very much worse). Percentage of participants with improvement rated as much better or a little better were reported for sleep onset,time, quality; morning awakening, tiredness and daytime sleepiness, physical condition.
Time frame: Week 4
Population: The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ramelteon | Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 | Sleep onset | 69.6 percentage of participants |
| Ramelteon | Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 | Sleep time | 63.8 percentage of participants |
| Ramelteon | Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 | Sleep quality | 64.8 percentage of participants |
| Ramelteon | Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 | Morning awakening | 54.0 percentage of participants |
| Ramelteon | Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 | Morning tiredness | 52.9 percentage of participants |
| Ramelteon | Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 | Daytime sleepiness | 51.9 percentage of participants |
| Ramelteon | Percentage of Participants Who Responded With Improvement on the Patient Global Impression (PGI) Scale at Week 4 | Daytime physical condition/function | 55.8 percentage of participants |
Secondary
Sleep Status: Number of Awakenings
Sleep status of participants was assessed and summarized by calculating the number of times participants had awaken from the time of start of the investigation.
Time frame: Baseline and Week 4
Population: The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ramelteon | Sleep Status: Number of Awakenings | Baseline | 2.1 number of awakenings | Standard Deviation 1.6 |
| Ramelteon | Sleep Status: Number of Awakenings | Week 4 | 1.2 number of awakenings | Standard Deviation 1.2 |
Secondary
Sleep Status: Sleep Onset Latency
Sleep status was determined by measuring the sleep onset latency, defined as the length of time taken from lying down for the night until sleep onset.
Time frame: Baseline and Week 4
Population: The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ramelteon | Sleep Status: Sleep Onset Latency | Baseline | 89.8 minutes | Standard Deviation 66.7 |
| Ramelteon | Sleep Status: Sleep Onset Latency | Week 4 | 47.1 minutes | Standard Deviation 46.2 |
Secondary
Sleep Status: Total Sleep Time
Sleep status was determined by measuring the total sleep time, defined as the amount of actual sleep time during a sleep episode.
Time frame: Baseline and Week 4
Population: The efficacy assessment population was defined as participants whose efficacy data at baseline and at least 1 post-baseline time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ramelteon | Sleep Status: Total Sleep Time | Week 4 | 7.31 hours | Standard Deviation 1.72 |
| Ramelteon | Sleep Status: Total Sleep Time | Baseline | 6.49 hours | Standard Deviation 2 |