Chronic Insomnia
Conditions
Keywords
Chronic Insomnia, Sleep Initiation and Maintenance Disorder, Drug Therapy
Brief summary
The purpose of this study is to assess whether ramelteon, once daily (QD), can facilitate the discontinuation of zolpidem in subjects with chronic insomnia.
Detailed description
Approximately 60 to 70 million adults in the United States alone are affected by insomnia. Daytime symptoms of insomnia include tiredness, lack of energy, difficulty concentrating, and irritability. Recent epidemiologic research focusing on the quality of life has identified significant insomnia-related morbidities that relate to work productivity, health care utilization, and risk of depression. Insomnia is associated with diminished work output, absenteeism, and greater rates of accidents. Zolpidem is the most commonly prescribed hypnotic in the United States for patients suffering from insomnia. The purpose of this study is to assess whether ramelteon therapy can facilitate the discontinuation of benzodiazepine therapy in long term users. Subject participation in this study is anticipated to be about 17 weeks. Subjects were screened and enrolled in a 4-week placebo run-in period, may have been randomized to a 10-week double-blind treatment period, and may have completed with a 2-week open-label treatment period. In the double-blind treatment period, subjects were randomized to one of two treatments: either ramelteon 8 mg tablets taken orally once-daily with concomitant current zolpidem therapy or to placebo-matching tablets once daily with concomitant current zolpidem therapy. Subjects incrementally reduced zolpidem therapy by dose, frequency, or both for up to 10 weeks. Only those subjects who completed the double-blind treatment period and had achieved a 50% reduction in zolpidem therapy during the double-blind treatment period participated in the open-label treatment period in which 8 mg ramelteon was administered. Zolpidem consumed during the open-label treatment period was recorded.
Interventions
DRUGRamelteon and zolpidem
Ramelteon 8 mg, tablets, orally, once daily and current zolpidem therapy incrementally reduced by dose, frequency, or both for up to 10 weeks.
DRUGPlacebo and zolpidem
Ramelteon placebo-matching tablets, orally, once daily and current zolpidem therapy incrementally reduced by dose, frequency, or both for up to 10 weeks.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic insomnia and taking greater than or equal to 10 mg zolpidem at least 4 times per week. * Has been prescribed zolpidem for difficulty in initiating sleep. * Must report chronic use of zolpidem greater than or equal to10 mg therapy for a minimum of 3 months prior to entry into Period 1 of the study. * Must have taken zolpidem greater than or equal to 10 mg therapy for at least 4 of 7 days each week of the 4 weeks immediately prior to entry into the double blind phase, Period 2. * Expressed a willingness to discontinue zolpidem therapy. * Habitual bedtime is between 9:00 PM and 1:00 AM based on sleep history. * Negative test result for hepatitis B surface antigen and hepatitis C virus antibody. * Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
Exclusion criteria
* Known hypersensitivity to ramelteon, zolpidem, or melatonin. * Participated in any other investigational study and/or taken any investigational drug within 30 days prior to the first dose of run-in study medication. * Sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the first night of run-in study medication. * History of fibromyalgia, history of seizures, sleep apnea, restless leg syndrome, periodic leg syndrome, chronic obstructive pulmonary disease, schizophrenia, bipolar disorder, mental retardation, or cognitive disorder. * History of drug addiction or drug abuse within the past 12 months. * History of alcohol abuse within the past 12 months, as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition revised and/or regularly consumes more than 2 alcoholic drinks per day. * Current significant hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological, or metabolic disease, unless currently controlled and stable with protocol-allowed medication, within 30 days prior to the first night of run-in study medication. * Body mass index of less than 18 or greater than 34 (weight /height2). * Any clinically important abnormal finding as documented by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator. * Positive hepatitis panel. * Known history of human immunodeficiency virus. * Any additional conditions(s) that in the investigator's opinion would affect: * sleep/wake function * prohibit the subject from completing the study * indicate that continuation in the study would not be in the best interests of the subject. * Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication, including: * Melatonin * Anxiolytics * Antipsychotics * Over-the-counter and prescription sedatives * Hypnotics (excluding zolpidem) * Narcotic analgesics * Antidepressants * Beta-blockers (exception is that Atenolol is permissible) * Anticonvulsants * St. John's wort * Sedating H1 antihistamines * Kava-kava * Systemic steroids * Ginkgo-biloba * Respiratory stimulants * Over-the-counter and prescription diet aids * Sedating Decongestants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Discontinued Zolpidem Therapy | Week 10 | Participants reduced zolpidem incrementally from Week 3 to Week 10 of the double-blind treatment period (DBTP). A participant who did not take any zolpidem during the last 7 days of the DBTP was defined as having completely discontinued zolpidem by that time point. The number of subjects who discontinued zolpidem at the end of the DBTP was summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Zolpidem Dosage During Weeks 3-4 | Baseline and Weeks 3-4 | Dosages of zolpidem taken were recorded during Weeks 3-4 of the DBTP. Differences in dosages from baseline were summarized. Weekly dosage was calculated as total amount of zolpidem taken divided by the number of days within the phase, multiplied by 7. |
| Change From Baseline in Weekly Zolpidem Dosage During Weeks 5-6 | Baseline and Weeks 5-6 | Dosages of zolpidem taken were recorded during Weeks 5-6 of the DBTP. Differences in dosages from baseline were summarized. Weekly dosage was calculated as total amount of zolpidem taken divided by the number of days within the phase, multiplied by 7. |
| Change From Baseline in Weekly Zolpidem Dosage During Weeks 7-8 | Baseline and Weeks 7-8 | Dosages of zolpidem taken were recorded during Weeks 7-8 of the double blind period. Differences in dosages from baseline were summarized. |
| Change From Baseline in Weekly Zolpidem Dosage During Weeks 9-10 | Baseline and Weeks 9-10 | Dosages of zolpidem taken were recorded during Weeks 9-10 of the DBTP. Differences in dosages from baseline were summarized. Weekly dosage was calculated as total amount of zolpidem taken divided by the number of days within the phase, multiplied by 7. |
| Change From Baseline in Weekly Zolpidem Frequency During Weeks 1-2 | Baseline and Weeks 1-2 | The number of nights zolpidem was taken was recorded during Weeks 1-2 of the DBTP. Weekly frequency was calculated as the number of nights zolpidem was taken divided by the number of days within the period, multiplied by 7. Differences in frequency from BL were summarized. |
| Change From Baseline in Weekly Zolpidem Frequency During Weeks 3-4 | Weeks 3-4 | The number of nights zolpidem was taken was recorded during Weeks 3-4 of the DBTP. Weekly frequency was calculated as the number of nights zolpidem was taken divided by the number of days within the period, multiplied by 7. Differences in frequency from baseline were summarized. |
| Change From Baseline in Weekly Zolpidem Dosage During Weeks 1-2 | Baseline and Weeks 1-2 | Dosages of zolpidem taken were recorded during Weeks 1-2 of the DBTP. Differences in dosages from baseline were summarized. Weekly dosage was calculated as total amount of zolpidem taken divided by the number of days within the phase, multiplied by 7. |
| Change From Baseline in Weekly Zolpidem Frequency During Weeks 7-8 | Baseline and Weeks 7-8 | The number of nights zolpidem was taken was recorded during Weeks 7-8 of the DBTP. Weekly frequency was calculated as the number of nights zolpidem was taken divided by the number of days within the period, multiplied by 7. Differences in frequency from baseline were summarized. |
| Change From Baseline in Weekly Zolpidem Frequency During Weeks 9-10 | Baseline and Weeks 9-10 | The number of nights zolpidem was taken was recorded during Weeks 9-10 of the DBTP. Weekly frequency was calculated as the number of nights zolpidem was taken divided by the number of days within the period, multiplied by 7. Differences in frequency from baseline were summarized. |
| Participants Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation | Weeks 1-10 | Participants who took no zolpidem during the last 7 days of the DBTP were completely discontinued from zolpidem. Participants who completely discontinued zolpidem via reduction in zolpidem use frequency (alone) were not summarized. |
| Participants Who Achieved a 50% Reduction in Zolpidem Dosage at the End of the Double-Blind Treatment Period | Baseline and Week 10 | Participants who achieved a 50% reduction in zolpidem dosage (or frequency) at the end of the DBTP (ie, the end of Reduction Phase 4) were summarized. The reduction in dosage at Reduction Phase 4=\[1-(Reduction Phase 4 weekly dosage/baseline weekly dosage)\]\*100%. |
| Participants Who Achieved a 50% Reduction in Zolpidem Dosage at Any Time During the Double-Blind Treatment Period | Baseline and Weeks 1-10 | Participants who achieved a 50% reduction in zolpidem dosage at any previously defined 2-week period (ie, reduction phase) during the DBTP were summarized. The reduction in dosage at any time=\[1-(reduction phase weekly dosage/baseline weekly dosage)\]\*100%. |
| Change From Baseline in Weekly Zolpidem Frequency During Weeks 5-6 | Weeks 5-6 | The number of nights zolpidem was taken was recorded during Weeks 5-6 of the DBTP. Weekly frequency was calculated as the number of nights zolpidem was taken divided by the number of days within the period, multiplied by 7. Differences in frequency from baseline were summarized. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled at 38 investigative sites in the United States from 26 April 2007 to 28 May 2008.
Pre-assignment details
Subjects completed a 4-week single-blind placebo run-in period prior to randomization in the double-blind treatment period (DBTP). During this time they took placebo-matching tablets once-daily (QD) with concomitant current zolpidem therapy. Subjects used a daily subject diary to record zolpidem dose reduction, daily activities, and sleep quality.
Participants by arm
| Arm | Count |
|---|---|
| Ramelteon 8 mg QD Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP. | 65 |
| Placebo QD Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP. | 70 |
| Total | 135 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Treatment | Adverse Event | 1 | 2 |
| Double-Blind Treatment | Lack of Efficacy | 1 | 0 |
| Double-Blind Treatment | Lost to Follow-up | 2 | 3 |
| Double-Blind Treatment | Other | 6 | 5 |
| Double-Blind Treatment | Protocol Violation | 3 | 7 |
| Double-Blind Treatment | Randomized not treated | 1 | 0 |
| Double-Blind Treatment | Withdrawal by Subject | 4 | 8 |
| Open-Label Treatment | Withdrawal by Subject | 1 | 0 |
| Placebo Run-in | Adverse Event | 0 | 2 |
| Placebo Run-in | Entrance criteria not met | 0 | 45 |
| Placebo Run-in | Lost to Follow-up | 0 | 3 |
| Placebo Run-in | Missing | 0 | 2 |
| Placebo Run-in | Other | 0 | 6 |
| Placebo Run-in | Pregnancy | 0 | 1 |
| Placebo Run-in | Protocol Violation | 0 | 3 |
| Placebo Run-in | Withdrawal by Subject | 0 | 8 |
Baseline characteristics
| Characteristic | Placebo QD | Total | Ramelteon 8 mg QD |
|---|---|---|---|
| Age Continuous | 47.0 years STANDARD_DEVIATION 12.98 | 49.2 years STANDARD_DEVIATION 13.35 | 51.5 years STANDARD_DEVIATION 13.45 |
| Baseline average total daily zolpidem dosage ≤10 mg | 60 subjects | 116 subjects | 56 subjects |
| Baseline average total daily zolpidem dosage >10 mg | 10 subjects | 18 subjects | 8 subjects |
| Baseline average total daily zolpidem dosage Information not available | 0 subjects | 1 subjects | 1 subjects |
| Baseline weekly zolpidem dosage | 70.3 Dosage (mg) STANDARD_DEVIATION 20.37 | 69.5 Dosage (mg) STANDARD_DEVIATION 19.09 | 68.7 Dosage (mg) STANDARD_DEVIATION 17.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 19.0 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 116.0 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0.0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Subjects | 2.0 Subjects | 1 Subjects |
| Race/Ethnicity, Customized Black or African American | 9 Subjects | 14.0 Subjects | 5 Subjects |
| Race/Ethnicity, Customized Multiracial | 1 Subjects | 1.0 Subjects | 0 Subjects |
| Race/Ethnicity, Customized White | 59 Subjects | 118.0 Subjects | 59 Subjects |
| Sex: Female, Male Female | 49 Participants | 91.0 Participants | 42 Participants |
| Sex: Female, Male Male | 21 Participants | 44.0 Participants | 23 Participants |
| Use of pharmacological assistance to sleep >4 nights per week | 61 subjects | 118 subjects | 57 subjects |
| Use of pharmacological assistance to sleep 4 nights per week | 9 subjects | 17 subjects | 8 subjects |
| Weekly frequency zolpidem consumption 0-3 nights per week | 0 subjects | 0 subjects | 0 subjects |
| Weekly frequency zolpidem consumption 4 nights per week | 1 subjects | 3 subjects | 2 subjects |
| Weekly frequency zolpidem consumption 5 nights per week | 9 subjects | 17 subjects | 8 subjects |
| Weekly frequency zolpidem consumption 6 nights per week | 7 subjects | 15 subjects | 8 subjects |
| Weekly frequency zolpidem consumption 7 nights per week | 53 subjects | 99 subjects | 46 subjects |
| Weekly frequency zolpidem consumption Information not available | 0 subjects | 1 subjects | 1 subjects |
| Weekly frequency zolpidem consumption | 6.60 nights per week STANDARD_DEVIATION 0.769 | 6.57 nights per week STANDARD_DEVIATION 0.799 | 6.53 nights per week STANDARD_DEVIATION 0.835 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 64 | 7 / 70 |
| serious Total, serious adverse events | 0 / 64 | 1 / 70 |
Outcome results
Primary
Percentage of Participants Who Discontinued Zolpidem Therapy
Participants reduced zolpidem incrementally from Week 3 to Week 10 of the double-blind treatment period (DBTP). A participant who did not take any zolpidem during the last 7 days of the DBTP was defined as having completely discontinued zolpidem by that time point. The number of subjects who discontinued zolpidem at the end of the DBTP was summarized.
Time frame: Week 10
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramelteon 8 mg QD | Percentage of Participants Who Discontinued Zolpidem Therapy | 28.8 Percentage of participants |
| Placebo QD | Percentage of Participants Who Discontinued Zolpidem Therapy | 32.7 Percentage of participants |
p-value: 0.48495% CI: [0.27, 1.85]Regression, Logistic
Secondary
Change From Baseline in Weekly Zolpidem Dosage During Weeks 1-2
Dosages of zolpidem taken were recorded during Weeks 1-2 of the DBTP. Differences in dosages from baseline were summarized. Weekly dosage was calculated as total amount of zolpidem taken divided by the number of days within the phase, multiplied by 7.
Time frame: Baseline and Weeks 1-2
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg QD | Change From Baseline in Weekly Zolpidem Dosage During Weeks 1-2 | -11.8 Dose (mg) | Standard Error 3.06 |
| Placebo QD | Change From Baseline in Weekly Zolpidem Dosage During Weeks 1-2 | -11.6 Dose (mg) | Standard Error 3.11 |
p-value: 0.94695% CI: [-6.23, 5.81]ANCOVA
Secondary
Change From Baseline in Weekly Zolpidem Dosage During Weeks 3-4
Dosages of zolpidem taken were recorded during Weeks 3-4 of the DBTP. Differences in dosages from baseline were summarized. Weekly dosage was calculated as total amount of zolpidem taken divided by the number of days within the phase, multiplied by 7.
Time frame: Baseline and Weeks 3-4
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg QD | Change From Baseline in Weekly Zolpidem Dosage During Weeks 3-4 | -35.3 Dose (mg) | Standard Error 2.89 |
| Placebo QD | Change From Baseline in Weekly Zolpidem Dosage During Weeks 3-4 | -35.6 Dose (mg) | Standard Error 2.93 |
p-value: 0.90195% CI: [-5.31, 6.03]ANCOVA
Secondary
Change From Baseline in Weekly Zolpidem Dosage During Weeks 5-6
Dosages of zolpidem taken were recorded during Weeks 5-6 of the DBTP. Differences in dosages from baseline were summarized. Weekly dosage was calculated as total amount of zolpidem taken divided by the number of days within the phase, multiplied by 7.
Time frame: Baseline and Weeks 5-6
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg QD | Change From Baseline in Weekly Zolpidem Dosage During Weeks 5-6 | -40.2 Dose (mg) | Standard Error 3.18 |
| Placebo QD | Change From Baseline in Weekly Zolpidem Dosage During Weeks 5-6 | -42.1 Dose (mg) | Standard Error 3.22 |
p-value: 0.53895% CI: [-4.32, 8.23]ANCOVA
Secondary
Change From Baseline in Weekly Zolpidem Dosage During Weeks 7-8
Dosages of zolpidem taken were recorded during Weeks 7-8 of the double blind period. Differences in dosages from baseline were summarized.
Time frame: Baseline and Weeks 7-8
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg QD | Change From Baseline in Weekly Zolpidem Dosage During Weeks 7-8 | -52.1 Dose (mg) | Standard Error 3.49 |
| Placebo QD | Change From Baseline in Weekly Zolpidem Dosage During Weeks 7-8 | -49.9 Dose (mg) | Standard Error 3.49 |
p-value: 0.51795% CI: [-9.09, 4.6]ANCOVA
Secondary
Change From Baseline in Weekly Zolpidem Dosage During Weeks 9-10
Dosages of zolpidem taken were recorded during Weeks 9-10 of the DBTP. Differences in dosages from baseline were summarized. Weekly dosage was calculated as total amount of zolpidem taken divided by the number of days within the phase, multiplied by 7.
Time frame: Baseline and Weeks 9-10
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg QD | Change From Baseline in Weekly Zolpidem Dosage During Weeks 9-10 | -60.6 Dose (mg) | Standard Error 3.27 |
| Placebo QD | Change From Baseline in Weekly Zolpidem Dosage During Weeks 9-10 | -60.7 Dose (mg) | Standard Error 3.31 |
p-value: 0.96595% CI: [-6.28, 6.56]ANCOVA
Secondary
Change From Baseline in Weekly Zolpidem Frequency During Weeks 1-2
The number of nights zolpidem was taken was recorded during Weeks 1-2 of the DBTP. Weekly frequency was calculated as the number of nights zolpidem was taken divided by the number of days within the period, multiplied by 7. Differences in frequency from BL were summarized.
Time frame: Baseline and Weeks 1-2
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg QD | Change From Baseline in Weekly Zolpidem Frequency During Weeks 1-2 | 0.13 nights per week | Standard Error 0.183 |
| Placebo QD | Change From Baseline in Weekly Zolpidem Frequency During Weeks 1-2 | 0.04 nights per week | Standard Error 0.186 |
p-value: 0.61795% CI: [-0.27, 0.45]ANCOVA
Secondary
Change From Baseline in Weekly Zolpidem Frequency During Weeks 3-4
The number of nights zolpidem was taken was recorded during Weeks 3-4 of the DBTP. Weekly frequency was calculated as the number of nights zolpidem was taken divided by the number of days within the period, multiplied by 7. Differences in frequency from baseline were summarized.
Time frame: Weeks 3-4
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg QD | Change From Baseline in Weekly Zolpidem Frequency During Weeks 3-4 | -0.08 nights per week | Standard Error 0.288 |
| Placebo QD | Change From Baseline in Weekly Zolpidem Frequency During Weeks 3-4 | -0.26 nights per week | Standard Error 0.292 |
p-value: 0.54195% CI: [-0.39, 0.74]ANCOVA
Secondary
Change From Baseline in Weekly Zolpidem Frequency During Weeks 5-6
The number of nights zolpidem was taken was recorded during Weeks 5-6 of the DBTP. Weekly frequency was calculated as the number of nights zolpidem was taken divided by the number of days within the period, multiplied by 7. Differences in frequency from baseline were summarized.
Time frame: Weeks 5-6
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg QD | Change From Baseline in Weekly Zolpidem Frequency During Weeks 5-6 | -0.05 nights per week | Standard Error 0.396 |
| Placebo QD | Change From Baseline in Weekly Zolpidem Frequency During Weeks 5-6 | -0.60 nights per week | Standard Error 0.4 |
p-value: 0.16395% CI: [-0.23, 1.33]ANCOVA
Secondary
Change From Baseline in Weekly Zolpidem Frequency During Weeks 7-8
The number of nights zolpidem was taken was recorded during Weeks 7-8 of the DBTP. Weekly frequency was calculated as the number of nights zolpidem was taken divided by the number of days within the period, multiplied by 7. Differences in frequency from baseline were summarized.
Time frame: Baseline and Weeks 7-8
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg QD | Change From Baseline in Weekly Zolpidem Frequency During Weeks 7-8 | -1.10 nights per week | Standard Error 0.475 |
| Placebo QD | Change From Baseline in Weekly Zolpidem Frequency During Weeks 7-8 | -1.24 nights per week | Standard Error 0.475 |
p-value: 0.75795% CI: [-0.79, 1.08]ANCOVA
Secondary
Change From Baseline in Weekly Zolpidem Frequency During Weeks 9-10
The number of nights zolpidem was taken was recorded during Weeks 9-10 of the DBTP. Weekly frequency was calculated as the number of nights zolpidem was taken divided by the number of days within the period, multiplied by 7. Differences in frequency from baseline were summarized.
Time frame: Baseline and Weeks 9-10
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon 8 mg QD | Change From Baseline in Weekly Zolpidem Frequency During Weeks 9-10 | -2.22 nights per week | Standard Error 0.534 |
| Placebo QD | Change From Baseline in Weekly Zolpidem Frequency During Weeks 9-10 | -2.34 nights per week | Standard Error 0.542 |
p-value: 0.8295% CI: [-0.93, 1.17]ANCOVA
Secondary
Participants Who Achieved a 50% Reduction in Zolpidem Dosage at Any Time During the Double-Blind Treatment Period
Participants who achieved a 50% reduction in zolpidem dosage at any previously defined 2-week period (ie, reduction phase) during the DBTP were summarized. The reduction in dosage at any time=\[1-(reduction phase weekly dosage/baseline weekly dosage)\]\*100%.
Time frame: Baseline and Weeks 1-10
Population: Analysis was performed on all subjects who were randomized and received at least 1 dose of double-blind medication during the study. Subjects were analyzed by the treatment they were randomized to receive.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramelteon 8 mg QD | Participants Who Achieved a 50% Reduction in Zolpidem Dosage at Any Time During the Double-Blind Treatment Period | 50 participants |
| Placebo QD | Participants Who Achieved a 50% Reduction in Zolpidem Dosage at Any Time During the Double-Blind Treatment Period | 50 participants |
p-value: 0.38995% CI: [0.64, 3.13]Regression, Logistic
Secondary
Participants Who Achieved a 50% Reduction in Zolpidem Dosage at the End of the Double-Blind Treatment Period
Participants who achieved a 50% reduction in zolpidem dosage (or frequency) at the end of the DBTP (ie, the end of Reduction Phase 4) were summarized. The reduction in dosage at Reduction Phase 4=\[1-(Reduction Phase 4 weekly dosage/baseline weekly dosage)\]\*100%.
Time frame: Baseline and Week 10
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, who had completed the DBTP, and who had sufficient zolpidem dosage data in the last 7 days of the DBTP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramelteon 8 mg QD | Participants Who Achieved a 50% Reduction in Zolpidem Dosage at the End of the Double-Blind Treatment Period | 48 participants |
| Placebo QD | Participants Who Achieved a 50% Reduction in Zolpidem Dosage at the End of the Double-Blind Treatment Period | 42 participants |
p-value: 0.28495% CI: [0.55, 7.34]Regression, Logistic
Secondary
Participants Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation
Participants who took no zolpidem during the last 7 days of the DBTP were completely discontinued from zolpidem. Participants who completely discontinued zolpidem via reduction in zolpidem use frequency (alone) were not summarized.
Time frame: Weeks 1-10
Population: Analysis was performed on all randomized subjects who took at least 1 dose of study drug, had completed the DBTP, and had sufficient zolpidem dosage data in the last 7 days of the DBTP. Estimates could not be reported with correct statistical inference due to small sample sizes by method of discontinuation (ie, most subjects reduced zolpidem dose).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ramelteon 8 mg QD | Participants Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation | Reduction in Dose | 12 participants |
| Ramelteon 8 mg QD | Participants Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation | Reduction in Dose and Frequency | 3 participants |
| Placebo QD | Participants Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation | Reduction in Dose | 8 participants |
| Placebo QD | Participants Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation | Reduction in Dose and Frequency | 8 participants |