Insomnia
Conditions
Keywords
insomnia, primary insomnia, insomnia associated with psychiatric or physical disorder(s)
Brief summary
The purpose of this study is to evaluate the long-term safety of eszopiclone (2, 3 mg) in non-elderly patients with insomnia and eszopiclone (1, 2 mg) in elderly patients with insomnia.
Detailed description
This is a multicenter, randomized, double-blinded study to evaluate the long-term safety of SEP-190 (2, 3 mg) in non-elderly patients with insomnia and SEP-190 (1, 2 mg) in elderly patients with insomnia.
Interventions
DRUGEszopiclone 1 mg- Elderly
Elderly participants: Eszopiclone 1 mg tablet and 1 tablet of placebo 2 mg daily by mouth at bedtime for 24 weeks. Dose escalation occurred after 4 weeks of treatment. Participants received 1 mg tablet additionally until the end of study treatment.
DRUGEszopiclone 2 mg- Elderly
Elderly participants: Eszopiclone 2 mg tablet and 1 tablet placebo 1 mg daily by mouth at bedtime for 24 weeks. Dose escalation occurred after 4 weeks of treatment. Participants received 1 mg placebo tablet additionally to maintain blind until the end of study treatment.
DRUGEszopiclone 3 mg- Non-elderly
Non-elderly participants: Eszopiclone 3 mg tablet and 1 tablet of placebo 2 mg daily by mouth at bedtime for 24 weeks. Dose escalation occurred after 4 weeks of treatment. Participants received 1 mg placebo tablet additionally to maintain blind until the end of study treatment.
DRUGEszopiclone 2 mg- Non-elderly
Non-elderly participants: Eszopiclone 2 mg tablet and 1 tablet of placebo 3 mg daily by mouth at bedtime for 24 weeks. Dose escalation occurred after 4 weeks of treatment. Participants received 1 mg tablet additionally until the end of study treatment.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
1. Participants who submit written informed consent for study entry. 2. Participants aged greater than or equal to 20 and less than 85 years of age at the time of obtaining informed consent. 3. Participants diagnosed with primary insomnia based on the Diagnostic and Statistical Manual of Mental Disorders, text revision (DSM-IV-TR) Japanese version or diagnosed with insomnia associated with psychiatric or physical disorder(s). 4. Participants with both of the following conditions which are persistent for 4 weeks or longer before the start of observation period: * Total sleep time is less than or equal to 390 minutes for more than or equal to 3 days a week * Time to fall asleep taking more than or equal to 30 minutes for more than or equal to 3 days a week 5. Participants with data at least 2 consecutive days in diary entries during observation period and confirmed to meet the following two criteria: * Total sleep time of less than or equal to 390 minutes for more than or equal to 3 days a week * Time to fall asleep taking more than or equal to 30 minutes for more than or equal to 3 days a week
Exclusion criteria
1. Participants with a present or history of the following disease specified in Mini-International Neuropsychiatric Interview (M.I.N.I.) Japanese version 5.0: * Risk of suicide * (Mild) manic episode * Post-traumatic stress disorder (PTSD) * Alcohol dependence and abuse * Drug (non-alcohol) dependence and abuse * Anorexia nervosa * Bulimia nervosa * Anti-social personality disorder 2. Participants with pharmacologically induced insomnia (drug-induced insomnia). 3. Participants with comorbid primary sleep disorders (circadian rhythm disorder, restless legs movement syndrome, periodic limb movement disorder, sleep apnea syndrome, etc.) other than primary insomnia. 4. Participants with symptoms that significantly disturb sleep such as pain, fever, diarrhea, frequent micturation, and cough. 5. Participants with unstable primary disease presenting insomnia during 4 weeks before the start of observation period. 6. Participants with organic mental disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Up to 25 weeks (24 weeks treatment period & 1 week follow-up) | Incidence of adverse events was defined as: (number of participants with adverse events/ number of participants analyzed in the safety analysis set)\*100. An adverse event was defined as any unwanted or untoward disease or its symptom, sign, or abnormality in laboratory parameters in a subject who receives a study drug. An adverse event does not necessarily have a causal relationship with the study drug. The investigator or subinvestigator evaluated adverse events and recorded the results in the case report form (CRF). The investigator or subinvestigator recorded all adverse events occurring after the start of study treatment in the CRF, irrespective of the causal relationship with the study drug or the study procedures. All data collected from the follow-up was recorded in CRF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline In Sleep Latency | Baseline (screening period) and 4 weeks of treatment | Based on subjective symptoms, the participants recorded their sleep latency (the amount of time measured in minutes it takes to fall asleep) in a sleep diary questionnaire for the week preceding the start of the study treatment (the day on which the patient was enrolled in the treatment period), as well as between the day on which the study treatment started and the Week 4 visit. For pre-treatment (screening period), the representative value was calculated from the data of the 7 days preceding enrollment in the treatment period. A median of all the data between the day of enrollment in the treatment period and the day before dose escalation judgment was presented as the data of the overall period. The change was calculated as the sleep latency of the overall period assessment - sleep latency at baseline (screening period). |
| Mean Change From Baseline in Wake Time After Sleep Onset (WASO) | Baseline (screening period) and 4 weeks of treatment | Based on subjective symptoms, the participants recorded their WASO defined as total awakening time from falling asleep to final awakening in a sleep diary questionnaire for the week preceding the start of the study treatment (the day on which the patient was enrolled in the treatment period), as well as between the day on which the study treatment started and the Week 4 visit. For pre-treatment (screening period), the representative value was calculated from the data of the 7 days preceding enrollment in the treatment period. A median of all the data between the day of enrollment in the treatment period and the day before dose escalation judgment was presented as the data of the overall period. The change was calculated as the WASO of the overall period assessment - WASO at baseline (screening period). |
| Mean Change From Baseline in Total Sleep Time | Baseline (screening period) and 4 weeks of treatment | Based on subjective symptoms, the participants recorded their total sleep time defined as total sleeping time from bedtime to final awakening in a sleep diary questionnaire for the week preceding the start of the study treatment (the day on which the patient was enrolled in the treatment period), as well as between the day on which the study treatment started and the Week 4 visit. For pre-treatment (screening period), the representative value was calculated from the data of the 7 days preceding enrollment in the treatment period. A median of all the data between the day of enrollment in the treatment period and the day before dose escalation judgment was presented as the data of the overall period. The change was calculated as the total sleep time of the overall period assessment - total sleep time at baseline (screening period). |
| Mean Change From Baseline in Total Number of Awakenings | Baseline (screening period) and 4 weeks of treatment | Based on subjective symptoms, the participants recorded their number of awakenings defined as total number of spontaneous awakenings from falling asleep to final awakening in a sleep diary questionnaire for the week preceding the start of the study treatment (the day on which the patient was enrolled in the treatment period), as well as between the day on which the study treatment started and the Week 4 visit. For pre-treatment (screening period), the representative value was calculated from the data of the 7 days preceding enrollment in the treatment period. A median of all the data between the day of enrollment in the treatment period and the day before dose escalation judgment was presented as the data of the overall period. The change was calculated as the total number of awakenings of the overall period assessment - total number of awakenings at baseline (screening period). |
Countries
Japan
Participant flow
Pre-assignment details
181 non-elderly & 188 elderly participants were enrolled in the screening period 1 week prior to the first dose. Among these, 20 non-elderly & 24 elderly participants discontinued during the screening period. 161 non-elderly and 164 elderly participants enrolled. 1 elderly participant enrolled for treatment did not receive treatment.
Participants by arm
| Arm | Count |
|---|---|
| Eszopiclone 1 mg- Elderly Elderly participants: Eszopiclone 1 mg tablet and 1 tablet of placebo 2 mg daily by mouth at bedtime for 24 weeks.
Dose escalation occurred after 4 weeks of treatment. Participants received 1 mg tablet additionally until the end of study treatment. | 80 |
| Eszopiclone 2 mg- Elderly Elderly participants: Eszopiclone 2 mg tablet and 1 tablet placebo 1 mg daily by mouth at bedtime for 24 weeks.
Dose escalation occurred after 4 weeks of treatment. Participants received 1 mg placebo tablet additionally to maintain blind until the end of study treatment. | 83 |
| Eszopiclone 2 mg- Non-elderly Non-elderly participants: Eszopiclone 2 mg tablet and 1 tablet of placebo 3 mg daily by mouth at bedtime for 24 weeks.
Dose escalation occurred after 4 weeks of treatment. Participants received 1 mg tablet additionally until the end of study treatment. | 84 |
| Eszopiclone 3 mg- Non-elderly Non-elderly participants: Eszopiclone 3 mg tablet and 1 tablet of placebo 2 mg daily by mouth at bedtime for 24 weeks.
Dose escalation occurred after 4 weeks of treatment. Participants received 1 mg placebo tablet additionally to maintain blind until the end of study treatment. | 77 |
| Total | 324 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 4 | 4 |
| Overall Study | Investigator judgment | 2 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 9 | 9 | 6 |
Baseline characteristics
| Characteristic | Eszopiclone 1 mg- Elderly | Eszopiclone 2 mg- Elderly | Eszopiclone 2 mg- Non-elderly | Eszopiclone 3 mg- Non-elderly | Total |
|---|---|---|---|---|---|
| Age Continuous | 70.4 years STANDARD_DEVIATION 4.5 | 70.7 years STANDARD_DEVIATION 4.7 | 40.1 years STANDARD_DEVIATION 10.8 | 41.9 years STANDARD_DEVIATION 11.5 | 55.6 years STANDARD_DEVIATION 17.1 |
| Sex: Female, Male Female | 45 Participants | 49 Participants | 55 Participants | 36 Participants | 185 Participants |
| Sex: Female, Male Male | 35 Participants | 34 Participants | 29 Participants | 41 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 69 / 84 | 67 / 77 | 66 / 81 | 66 / 83 |
| serious Total, serious adverse events | 2 / 84 | 2 / 77 | 3 / 81 | 3 / 83 |
Outcome results
Primary
Incidence of Adverse Events
Incidence of adverse events was defined as: (number of participants with adverse events/ number of participants analyzed in the safety analysis set)\*100. An adverse event was defined as any unwanted or untoward disease or its symptom, sign, or abnormality in laboratory parameters in a subject who receives a study drug. An adverse event does not necessarily have a causal relationship with the study drug. The investigator or subinvestigator evaluated adverse events and recorded the results in the case report form (CRF). The investigator or subinvestigator recorded all adverse events occurring after the start of study treatment in the CRF, irrespective of the causal relationship with the study drug or the study procedures. All data collected from the follow-up was recorded in CRF.
Time frame: Up to 25 weeks (24 weeks treatment period & 1 week follow-up)
Population: Safety analysis set: All 161 non-elderly participants who were enrolled in the treatment period were included. All 164 elderly patients who were enrolled in the treatment period were included. The participant who was excluded from the efficacy analysis set was included in the safety analysis set because the participant had evaluable safety data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eszopiclone 1 mg- Elderly | Incidence of Adverse Events | 81.5 Percentage of Participants |
| Eszopiclone 2 mg- Elderly | Incidence of Adverse Events | 79.5 Percentage of Participants |
| Eszopiclone 2 mg- Non-elderly | Incidence of Adverse Events | 82.1 Percentage of Participants |
| Eszopiclone 3 mg- Non-elderly | Incidence of Adverse Events | 87.0 Percentage of Participants |
Secondary
Mean Change From Baseline In Sleep Latency
Based on subjective symptoms, the participants recorded their sleep latency (the amount of time measured in minutes it takes to fall asleep) in a sleep diary questionnaire for the week preceding the start of the study treatment (the day on which the patient was enrolled in the treatment period), as well as between the day on which the study treatment started and the Week 4 visit. For pre-treatment (screening period), the representative value was calculated from the data of the 7 days preceding enrollment in the treatment period. A median of all the data between the day of enrollment in the treatment period and the day before dose escalation judgment was presented as the data of the overall period. The change was calculated as the sleep latency of the overall period assessment - sleep latency at baseline (screening period).
Time frame: Baseline (screening period) and 4 weeks of treatment
Population: Efficacy analysis set: all of the 161 non-elderly participants who were enrolled in the treatment period. Among the 164 elderly participants who were enrolled in the treatment period, 163 (80 in the 1 mg group and 83 in the 2 mg group) were included in the efficacy set, excluding 1 participant in the 1 mg group who had no evaluable efficacy data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszopiclone 1 mg- Elderly | Mean Change From Baseline In Sleep Latency | Baseline | 65.5 minutes | Standard Deviation 40.5 |
| Eszopiclone 1 mg- Elderly | Mean Change From Baseline In Sleep Latency | Overall Period (Change From Baseline) | -32.1 minutes | Standard Deviation 35.6 |
| Eszopiclone 2 mg- Elderly | Mean Change From Baseline In Sleep Latency | Overall Period (Change From Baseline) | -37.0 minutes | Standard Deviation 42.7 |
| Eszopiclone 2 mg- Elderly | Mean Change From Baseline In Sleep Latency | Baseline | 70.7 minutes | Standard Deviation 47.1 |
| Eszopiclone 2 mg- Non-elderly | Mean Change From Baseline In Sleep Latency | Baseline | 71.8 minutes | Standard Deviation 53.5 |
| Eszopiclone 2 mg- Non-elderly | Mean Change From Baseline In Sleep Latency | Overall Period (Change From Baseline) | -36.7 minutes | Standard Deviation 51.8 |
| Eszopiclone 3 mg- Non-elderly | Mean Change From Baseline In Sleep Latency | Baseline | 64.0 minutes | Standard Deviation 42.2 |
| Eszopiclone 3 mg- Non-elderly | Mean Change From Baseline In Sleep Latency | Overall Period (Change From Baseline) | -32.8 minutes | Standard Deviation 35.4 |
Secondary
Mean Change From Baseline in Total Number of Awakenings
Based on subjective symptoms, the participants recorded their number of awakenings defined as total number of spontaneous awakenings from falling asleep to final awakening in a sleep diary questionnaire for the week preceding the start of the study treatment (the day on which the patient was enrolled in the treatment period), as well as between the day on which the study treatment started and the Week 4 visit. For pre-treatment (screening period), the representative value was calculated from the data of the 7 days preceding enrollment in the treatment period. A median of all the data between the day of enrollment in the treatment period and the day before dose escalation judgment was presented as the data of the overall period. The change was calculated as the total number of awakenings of the overall period assessment - total number of awakenings at baseline (screening period).
Time frame: Baseline (screening period) and 4 weeks of treatment
Population: Efficacy analysis set: all of the 161 non-elderly participants who were enrolled in the treatment period. Among the 164 elderly participants who were enrolled in the treatment period, 163 (80 in the 1 mg group and 83 in the 2 mg group) were included in the efficacy set, excluding 1 participant in the 1 mg group who had no evaluable efficacy data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszopiclone 1 mg- Elderly | Mean Change From Baseline in Total Number of Awakenings | Baseline | 1.8 Number of Awakenings | Standard Deviation 0.9 |
| Eszopiclone 1 mg- Elderly | Mean Change From Baseline in Total Number of Awakenings | Overall Period (Change From Baseline) | -0.5 Number of Awakenings | Standard Deviation 0.7 |
| Eszopiclone 2 mg- Elderly | Mean Change From Baseline in Total Number of Awakenings | Overall Period (Change From Baseline) | -0.5 Number of Awakenings | Standard Deviation 0.8 |
| Eszopiclone 2 mg- Elderly | Mean Change From Baseline in Total Number of Awakenings | Baseline | 1.9 Number of Awakenings | Standard Deviation 1 |
| Eszopiclone 2 mg- Non-elderly | Mean Change From Baseline in Total Number of Awakenings | Baseline | 1.7 Number of Awakenings | Standard Deviation 0.9 |
| Eszopiclone 2 mg- Non-elderly | Mean Change From Baseline in Total Number of Awakenings | Overall Period (Change From Baseline) | -0.7 Number of Awakenings | Standard Deviation 0.9 |
| Eszopiclone 3 mg- Non-elderly | Mean Change From Baseline in Total Number of Awakenings | Baseline | 1.6 Number of Awakenings | Standard Deviation 1.1 |
| Eszopiclone 3 mg- Non-elderly | Mean Change From Baseline in Total Number of Awakenings | Overall Period (Change From Baseline) | -0.7 Number of Awakenings | Standard Deviation 0.9 |
Secondary
Mean Change From Baseline in Total Sleep Time
Based on subjective symptoms, the participants recorded their total sleep time defined as total sleeping time from bedtime to final awakening in a sleep diary questionnaire for the week preceding the start of the study treatment (the day on which the patient was enrolled in the treatment period), as well as between the day on which the study treatment started and the Week 4 visit. For pre-treatment (screening period), the representative value was calculated from the data of the 7 days preceding enrollment in the treatment period. A median of all the data between the day of enrollment in the treatment period and the day before dose escalation judgment was presented as the data of the overall period. The change was calculated as the total sleep time of the overall period assessment - total sleep time at baseline (screening period).
Time frame: Baseline (screening period) and 4 weeks of treatment
Population: Efficacy analysis set: all of the 161 non-elderly participants who were enrolled in the treatment period. Among the 164 elderly participants who were enrolled in the treatment period, 163 (80 in the 1 mg group and 83 in the 2 mg group) were included in the efficacy set, excluding 1 participant in the 1 mg group who had no evaluable efficacy data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszopiclone 1 mg- Elderly | Mean Change From Baseline in Total Sleep Time | Baseline | 314.2 minutes | Standard Deviation 73.2 |
| Eszopiclone 1 mg- Elderly | Mean Change From Baseline in Total Sleep Time | Overall Period (Change From Baseline) | 63.6 minutes | Standard Deviation 64.1 |
| Eszopiclone 2 mg- Elderly | Mean Change From Baseline in Total Sleep Time | Overall Period (Change From Baseline) | 74.2 minutes | Standard Deviation 61.4 |
| Eszopiclone 2 mg- Elderly | Mean Change From Baseline in Total Sleep Time | Baseline | 307.9 minutes | Standard Deviation 60 |
| Eszopiclone 2 mg- Non-elderly | Mean Change From Baseline in Total Sleep Time | Baseline | 290.7 minutes | Standard Deviation 44 |
| Eszopiclone 2 mg- Non-elderly | Mean Change From Baseline in Total Sleep Time | Overall Period (Change From Baseline) | 70.2 minutes | Standard Deviation 50.2 |
| Eszopiclone 3 mg- Non-elderly | Mean Change From Baseline in Total Sleep Time | Baseline | 308.2 minutes | Standard Deviation 57.7 |
| Eszopiclone 3 mg- Non-elderly | Mean Change From Baseline in Total Sleep Time | Overall Period (Change From Baseline) | 61.8 minutes | Standard Deviation 54.7 |
Secondary
Mean Change From Baseline in Wake Time After Sleep Onset (WASO)
Based on subjective symptoms, the participants recorded their WASO defined as total awakening time from falling asleep to final awakening in a sleep diary questionnaire for the week preceding the start of the study treatment (the day on which the patient was enrolled in the treatment period), as well as between the day on which the study treatment started and the Week 4 visit. For pre-treatment (screening period), the representative value was calculated from the data of the 7 days preceding enrollment in the treatment period. A median of all the data between the day of enrollment in the treatment period and the day before dose escalation judgment was presented as the data of the overall period. The change was calculated as the WASO of the overall period assessment - WASO at baseline (screening period).
Time frame: Baseline (screening period) and 4 weeks of treatment
Population: Efficacy analysis set: all of the 161 non-elderly participants who were enrolled in the treatment period. Among the 164 elderly participants who were enrolled in the treatment period, 163 (80 in the 1 mg group and 83 in the 2 mg group) were included in the efficacy set, excluding 1 participant in the 1 mg group who had no evaluable efficacy data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszopiclone 1 mg- Elderly | Mean Change From Baseline in Wake Time After Sleep Onset (WASO) | Baseline | 61.6 minutes | Standard Deviation 52.3 |
| Eszopiclone 1 mg- Elderly | Mean Change From Baseline in Wake Time After Sleep Onset (WASO) | Overall Period (Change From Baseline) | -30.8 minutes | Standard Deviation 39.9 |
| Eszopiclone 2 mg- Elderly | Mean Change From Baseline in Wake Time After Sleep Onset (WASO) | Overall Period (Change From Baseline) | -35.1 minutes | Standard Deviation -25 |
| Eszopiclone 2 mg- Elderly | Mean Change From Baseline in Wake Time After Sleep Onset (WASO) | Baseline | 68.8 minutes | Standard Deviation 63 |
| Eszopiclone 2 mg- Non-elderly | Mean Change From Baseline in Wake Time After Sleep Onset (WASO) | Baseline | 53.2 minutes | Standard Deviation 41.8 |
| Eszopiclone 2 mg- Non-elderly | Mean Change From Baseline in Wake Time After Sleep Onset (WASO) | Overall Period (Change From Baseline) | -32.4 minutes | Standard Deviation 36.9 |
| Eszopiclone 3 mg- Non-elderly | Mean Change From Baseline in Wake Time After Sleep Onset (WASO) | Baseline | 42.3 minutes | Standard Deviation 40.8 |
| Eszopiclone 3 mg- Non-elderly | Mean Change From Baseline in Wake Time After Sleep Onset (WASO) | Overall Period (Change From Baseline) | -23.3 minutes | Standard Deviation 31.1 |