Chronic Insomnia
Conditions
Keywords
chronic insomnia
Brief summary
This study is being conducted to evaluate the effectiveness of ramelteon 8mgs in the treatment of insomnia in patients that have completed their first chemotherapy treatment for breast cancer.
Detailed description
Phase IV, randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy of ramelteon 8mgs in the treatment of insomnia in patients with breast cancer.
Interventions
DRUGPlacebo
Placebo taken 30 minutes before bedtime days 1-28 of treatment period
DRUGRamelteon
8 mgs daily for days 1-28 of treatment period
Sponsors
Takeda Pharmaceuticals North America, Inc.
Accelerated Community Oncology Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Female patients aged 21-60 years old * Have a negative serum or urine pregnancy test for women of child-bearing potential * Have a three-month or longer history of insomnia * Self-report \< 6.5 hours of total sleep time, in addition to a sleep efficiency of less than 85%, averaged over two weeks of screening * A score of less than 60 on the Zung Self-Rating Depression Scale * Self-report bedtimes that do not vary by more than two hours on five nights per week * Have completed chemotherapy for breast cancer less than two years prior to study drug administration * Have completed chemotherapy for breast cancer for at least two months prior to screening visit * Patients that are receiving Herceptin are eligible for study enrollment * Have completed radiation therapy for breast cancer for at least two months prior to screening visit * ECOG (Eastern Cooperative Oncology Group)score of 0-1 * Be able to read, understand, and provide written informed consent before enrolling in the study * Must be willing to comply with all study visits and comply with daily phone calls to the IVRS throughout the study * Agree to participate for the entire study period (about two months)
Exclusion criteria
* Metastatic disease * Pregnant or lactating female * Self-reports typical consumption of more than five alcoholic beverages on a single day or greater than 14 alcoholic beverages weekly * Self-reports use of products containing nicotine of greater than 15 cigarettes daily or cannot avoid products containing nicotine during sleep periods * Current use of any of the following medications, and cannot discontinue these medications for the duration of the study: Hypnotic medication, Anti-convulsants, Anxiolytics, Narcotic analgesics, Medications or supplements containing Melatonin, Ketaconazole and Fluconazole * Currently taking fluvoxamine, brand name Luvox * Have symptoms consistent with the diagnosis of any other sleep disorder other than insomnia (e.g. obstructive sleep apnea, narcolepsy, restless legs syndrome) * Currently on night or rotating shift work * Self-reports habitual napping of greater than one hour accumulated sleep on 4 or more days per week * Has a psychiatric illness that interferes with normal sleep-wake function (e.g. major depression, post-traumatic stress disorder) * A score of 60 or greater on the Zung Self-Rating Depression Scale * Has current unstable medical disorder, such as symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, or other serious medical condition as determined by the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Efficiency | Every morning during the screening, treatment, and withdrawal periods | Total time in bed is calculated as the time the subject got out of bed minus the time the subject went to bed. The total sleep time is reported by the subject. Percent sleep efficiency is calulated as 100\*(total sleep time divided by total time in bed). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative Sleep Parameters - Number of Awakenings | Every morning during the screening, treatment, and withdrawal periods | The subject reports how many times she woke up during the night. |
| Qualitative Evaluation of Sleep - Global Sleep Impression | Once during the withdrawal period | The Patient Global Impression is a 7-point scale which asks How much has your sleep improved? with the following anchors: no improvement, minimal improvement, slight improvement, moderate improvement, very good improvement, near complete improvement, and complete improvement. |
| Qualitative Evaluation of Sleep - Quality of Sleep | Every morning during the screening, treatment, and withdrawal periods | The subject rates the quality of her sleep on a scale of 0 through 10, where 0 is a very bad night of sleep and 10 is a very good night of sleep. |
| Quantitative Sleep Parameters - Total Sleep Time | Every morning during the screening, treatment, and withdrawal periods | The subject reports how many hours of sleep she got. |
| Daytime Function - Despair | Once during the screening period; once during the treatment period; twice during the withdrawal period for a total of 4 assessments | The subject rates 7 questions related to despair on a scale of 0 through 10 for each question, where 0 is not bad and 10 is as bad as possible. The scores of these 7 questions are combined and normalized, and used to describe despair. |
| Daytime Function - Distress | Once during the screening period; once during the treatment period; twice during the withdrawal period for a total of 4 assessments | The subject rates 4 questions related to distress on a scale of 0 through 10 for each question, where 0 is not bad and 10 is as bad as possible. The scores of these 4 questions are combined and normalized, and used to describe distress. |
| Daytime Function - Fatigue | Once during the screening period; once during the treatment period; twice during the withdrawal period for a total of 4 assessments | The subject rates her fatigue on a scale of 0 through 10, where 0 is not a problem and 10 is as bad as possible. |
Countries
United States
Participant flow
Recruitment details
10 community oncology research sites across the United States within Accelerated Community Oncology Research Network (ACORN) participated in this study. Enrollment started in August 2006 and closed in August 2008.
Pre-assignment details
After consent, subjects underwent a 2 week screening period to see if they met the criteria for insomnia and to assess compliance with daily Interactive Voice Recognition System (IVRS) calls.
Participants by arm
| Arm | Count |
|---|---|
| 1 (Placebo) Patients will take placebo 30 minutes before bedtime days 1-28 of treatment period. | 7 |
| 2 (Ramelteon) Patients will take 8 mgs of ramelteon 30 minutes before bedtime days 1-28 of treatment period. | 9 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Screening Period (Pre-randomization) | Non-compliance | 1 | 0 |
| Screening Period (Pre-randomization) | Screen failure | 3 | 0 |
| Screening Period (Pre-randomization) | Withdrawal by Subject | 2 | 0 |
| Treatment Period | Non-compliance | 1 | 1 |
| Treatment Period | Withdrawal by Subject | 0 | 1 |
| Withdrawal Period | Non-compliance | 0 | 1 |
Baseline characteristics
| Characteristic | 1 (Placebo) | 2 (Ramelteon) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 9 Participants | 16 Participants |
| Age Continuous | 51.69 Years STANDARD_DEVIATION 5.98 | 49.11 Years STANDARD_DEVIATION 6.78 | 50.24 Years STANDARD_DEVIATION 6.37 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 7 Participants | 14 Participants |
| Region of Enrollment United States | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 7 | 4 / 9 |
| serious Total, serious adverse events | 0 / 7 | 0 / 9 |
Outcome results
Primary
Sleep Efficiency
Total time in bed is calculated as the time the subject got out of bed minus the time the subject went to bed. The total sleep time is reported by the subject. Percent sleep efficiency is calulated as 100\*(total sleep time divided by total time in bed).
Time frame: Every morning during the screening, treatment, and withdrawal periods
Population: Screening period: 14 patients with 6 treated with Placebo and 8 with Ramelteon. Treatment period: 13 patients with 5 treated with Placebo and 8 with Ramelteon. Withdrawal period: 10 patients with 4 treated with Placebo and 6 with Ramelteon.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 (Placebo) | Sleep Efficiency | Screening Period | 59.62 Percent sleep efficiency | Standard Deviation 16.72 |
| 1 (Placebo) | Sleep Efficiency | Treatment Period | 72.09 Percent sleep efficiency | Standard Deviation 9.38 |
| 1 (Placebo) | Sleep Efficiency | Withdrawal Period | 75.87 Percent sleep efficiency | Standard Deviation 11.85 |
| 2 (Ramelteon) | Sleep Efficiency | Screening Period | 70.16 Percent sleep efficiency | Standard Deviation 12.55 |
| 2 (Ramelteon) | Sleep Efficiency | Treatment Period | 71.26 Percent sleep efficiency | Standard Deviation 14.54 |
| 2 (Ramelteon) | Sleep Efficiency | Withdrawal Period | 67.48 Percent sleep efficiency | Standard Deviation 14.19 |
Secondary
Daytime Function - Despair
The subject rates 7 questions related to despair on a scale of 0 through 10 for each question, where 0 is not bad and 10 is as bad as possible. The scores of these 7 questions are combined and normalized, and used to describe despair.
Time frame: Once during the screening period; once during the treatment period; twice during the withdrawal period for a total of 4 assessments
Population: Screening period: 11 patients with 6 treated with Placebo and 5 with Ramelteon. Treatment period: 9 patients with 4 treated with Placebo and 5 with Ramelteon. Withdrawal period: 8 patients with 4 treated with Placebo and 4 with Ramelteon.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 (Placebo) | Daytime Function - Despair | Screening Period | 47.07 Units on a Scale | Standard Deviation 10.17 |
| 1 (Placebo) | Daytime Function - Despair | Treatment Period | 42.92 Units on a Scale | Standard Deviation 0 |
| 1 (Placebo) | Daytime Function - Despair | Withdrawal Period | 49.38 Units on a Scale | Standard Deviation 12.91 |
| 2 (Ramelteon) | Daytime Function - Despair | Screening Period | 46.02 Units on a Scale | Standard Deviation 6.92 |
| 2 (Ramelteon) | Daytime Function - Despair | Treatment Period | 45.15 Units on a Scale | Standard Deviation 5 |
| 2 (Ramelteon) | Daytime Function - Despair | Withdrawal Period | 42.92 Units on a Scale | Standard Deviation 0 |
Secondary
Daytime Function - Distress
The subject rates 4 questions related to distress on a scale of 0 through 10 for each question, where 0 is not bad and 10 is as bad as possible. The scores of these 4 questions are combined and normalized, and used to describe distress.
Time frame: Once during the screening period; once during the treatment period; twice during the withdrawal period for a total of 4 assessments
Population: Screening period: 11 patients with 6 treated with Placebo and 5 with Ramelteon. Treatment period: 9 patients with 4 treated with Placebo and 5 with Ramelteon. Withdrawal period: 8 patients with 4 treated with Placebo and 4 with Ramelteon.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 (Placebo) | Daytime Function - Distress | Screening Period | 42.91 Units on a Scale | Standard Deviation 12.2 |
| 1 (Placebo) | Daytime Function - Distress | Treatment Period | 37.93 Units on a Scale | Standard Deviation 0 |
| 1 (Placebo) | Daytime Function - Distress | Withdrawal Period | 45.40 Units on a Scale | Standard Deviation 14.94 |
| 2 (Ramelteon) | Daytime Function - Distress | Screening Period | 41.99 Units on a Scale | Standard Deviation 9.07 |
| 2 (Ramelteon) | Daytime Function - Distress | Treatment Period | 39.86 Units on a Scale | Standard Deviation 4.32 |
| 2 (Ramelteon) | Daytime Function - Distress | Withdrawal Period | 37.93 Units on a Scale | Standard Deviation 0 |
Secondary
Daytime Function - Fatigue
The subject rates her fatigue on a scale of 0 through 10, where 0 is not a problem and 10 is as bad as possible.
Time frame: Once during the screening period; once during the treatment period; twice during the withdrawal period for a total of 4 assessments
Population: Screening period: 12 patients with 6 treated with Placebo and 6 with Ramelteon. Treatment period: 11 patients with 4 treated with Placebo and 7 with Ramelteon. Withdrawal period: 8 patients with 4 treated with Placebo and 4 with Ramelteon.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 (Placebo) | Daytime Function - Fatigue | Screening Period | 3.06 Units on a Scale | Standard Deviation 2.36 |
| 1 (Placebo) | Daytime Function - Fatigue | Treatment Period | 2.42 Units on a Scale | Standard Deviation 0.79 |
| 1 (Placebo) | Daytime Function - Fatigue | Withdrawal Period | 3.38 Units on a Scale | Standard Deviation 2.43 |
| 2 (Ramelteon) | Daytime Function - Fatigue | Screening Period | 2.11 Units on a Scale | Standard Deviation 1.7 |
| 2 (Ramelteon) | Daytime Function - Fatigue | Treatment Period | 4.07 Units on a Scale | Standard Deviation 1.84 |
| 2 (Ramelteon) | Daytime Function - Fatigue | Withdrawal Period | 3.00 Units on a Scale | Standard Deviation 2.45 |
Secondary
Qualitative Evaluation of Sleep - Global Sleep Impression
The Patient Global Impression is a 7-point scale which asks How much has your sleep improved? with the following anchors: no improvement, minimal improvement, slight improvement, moderate improvement, very good improvement, near complete improvement, and complete improvement.
Time frame: Once during the withdrawal period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 (Placebo) | Qualitative Evaluation of Sleep - Global Sleep Impression | Moderate improvement | 3 Participants |
| 1 (Placebo) | Qualitative Evaluation of Sleep - Global Sleep Impression | Minimal improvement | 0 Participants |
| 1 (Placebo) | Qualitative Evaluation of Sleep - Global Sleep Impression | Slight improvement | 1 Participants |
| 1 (Placebo) | Qualitative Evaluation of Sleep - Global Sleep Impression | No improvement | 2 Participants |
| 1 (Placebo) | Qualitative Evaluation of Sleep - Global Sleep Impression | Complete improvement | 0 Participants |
| 2 (Ramelteon) | Qualitative Evaluation of Sleep - Global Sleep Impression | No improvement | 4 Participants |
| 2 (Ramelteon) | Qualitative Evaluation of Sleep - Global Sleep Impression | Complete improvement | 1 Participants |
| 2 (Ramelteon) | Qualitative Evaluation of Sleep - Global Sleep Impression | Moderate improvement | 0 Participants |
| 2 (Ramelteon) | Qualitative Evaluation of Sleep - Global Sleep Impression | Slight improvement | 0 Participants |
| 2 (Ramelteon) | Qualitative Evaluation of Sleep - Global Sleep Impression | Minimal improvement | 2 Participants |
Secondary
Qualitative Evaluation of Sleep - Quality of Sleep
The subject rates the quality of her sleep on a scale of 0 through 10, where 0 is a very bad night of sleep and 10 is a very good night of sleep.
Time frame: Every morning during the screening, treatment, and withdrawal periods
Population: Screening period: 14 patients with 6 treated with Placebo and 8 with Ramelteon. Treatment period: 13 patients with 5 treated with Placebo and 8 with Ramelteon. Withdrawal period: 10 patients with 4 treated with Placebo and 6 with Ramelteon.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 (Placebo) | Qualitative Evaluation of Sleep - Quality of Sleep | Screening Period | 4.60 Units on a Scale | Standard Deviation 1.32 |
| 1 (Placebo) | Qualitative Evaluation of Sleep - Quality of Sleep | Treatment Period | 5.47 Units on a Scale | Standard Deviation 1.25 |
| 1 (Placebo) | Qualitative Evaluation of Sleep - Quality of Sleep | Withdrawal Period | 6.59 Units on a Scale | Standard Deviation 2.06 |
| 2 (Ramelteon) | Qualitative Evaluation of Sleep - Quality of Sleep | Screening Period | 5.32 Units on a Scale | Standard Deviation 0.78 |
| 2 (Ramelteon) | Qualitative Evaluation of Sleep - Quality of Sleep | Treatment Period | 5.15 Units on a Scale | Standard Deviation 0.93 |
| 2 (Ramelteon) | Qualitative Evaluation of Sleep - Quality of Sleep | Withdrawal Period | 5.47 Units on a Scale | Standard Deviation 0.68 |
Secondary
Quantitative Sleep Parameters - Number of Awakenings
The subject reports how many times she woke up during the night.
Time frame: Every morning during the screening, treatment, and withdrawal periods
Population: Screening period: 14 patients with 6 treated with Placebo and 8 with Ramelteon. Treatment period: 13 patients with 5 treated with Placebo and 8 with Ramelteon. Withdrawal period: 10 patients with 4 treated with Placebo and 6 with Ramelteon.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 (Placebo) | Quantitative Sleep Parameters - Number of Awakenings | Screening Period | 2.62 Awakenings | Standard Deviation 0.46 |
| 1 (Placebo) | Quantitative Sleep Parameters - Number of Awakenings | Treatment Period | 2.28 Awakenings | Standard Deviation 0.37 |
| 1 (Placebo) | Quantitative Sleep Parameters - Number of Awakenings | Withdrawal Period | 2.19 Awakenings | Standard Deviation 1.18 |
| 2 (Ramelteon) | Quantitative Sleep Parameters - Number of Awakenings | Screening Period | 2.66 Awakenings | Standard Deviation 1.1 |
| 2 (Ramelteon) | Quantitative Sleep Parameters - Number of Awakenings | Treatment Period | 2.76 Awakenings | Standard Deviation 1.7 |
| 2 (Ramelteon) | Quantitative Sleep Parameters - Number of Awakenings | Withdrawal Period | 2.37 Awakenings | Standard Deviation 0.8 |
Secondary
Quantitative Sleep Parameters - Total Sleep Time
The subject reports how many hours of sleep she got.
Time frame: Every morning during the screening, treatment, and withdrawal periods
Population: Screening period: 14 patients with 6 treated with Placebo and 8 with Ramelteon. Treatment period: 13 patients with 5 treated with Placebo and 8 with Ramelteon. Withdrawal period: 10 patients with 4 treated with Placebo and 6 with Ramelteon.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 (Placebo) | Quantitative Sleep Parameters - Total Sleep Time | Screening Period | 5.02 Hours | Standard Deviation 1.62 |
| 1 (Placebo) | Quantitative Sleep Parameters - Total Sleep Time | Treatment Period | 5.94 Hours | Standard Deviation 1.2 |
| 1 (Placebo) | Quantitative Sleep Parameters - Total Sleep Time | Withdrawal Period | 5.57 Hours | Standard Deviation 0.5 |
| 2 (Ramelteon) | Quantitative Sleep Parameters - Total Sleep Time | Screening Period | 5.27 Hours | Standard Deviation 0.83 |
| 2 (Ramelteon) | Quantitative Sleep Parameters - Total Sleep Time | Treatment Period | 5.62 Hours | Standard Deviation 0.79 |
| 2 (Ramelteon) | Quantitative Sleep Parameters - Total Sleep Time | Withdrawal Period | 5.11 Hours | Standard Deviation 0.87 |