Back to resultsFacilitation of Zolpidem (≥10 mg) Discontinuation Through Use of Ramelteon in Subjects With Chronic Insomnia
Primary Purpose
Chronic Insomnia
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ramelteon and zolpidem
Placebo and zolpidem
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Insomnia focused on measuring Chronic Insomnia, Sleep Initiation and Maintenance Disorder, Drug Therapy
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ramelteon 8 mg QD and current Zolpidem therapy
Placebo QD and current Zolpidem therapy
Arm Description
Zolpidem therapy will be reduced by dose, frequency, or both for up to 10 weeks.
Zolpidem therapy will be reduced by dose, frequency, or both for up to 10 weeks.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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%.
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%.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00492232
Brief Title
Facilitation of Zolpidem (≥10 mg) Discontinuation Through Use of Ramelteon in Subjects With Chronic Insomnia
Official Title
Randomized, Double Blind, Placebo-Controlled Study to Assess Whether the Administration of Ramelteon Could Facilitate the Discontinuation of Zolpidem (Ambien®) ≥10 mg Therapy in Subjects With Chronic Insomnia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2010
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
May 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Insomnia
Keywords
Chronic Insomnia, Sleep Initiation and Maintenance Disorder, Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
135 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ramelteon 8 mg QD and current Zolpidem therapy
Arm Type
Experimental
Arm Description
Zolpidem therapy will be reduced by dose, frequency, or both for up to 10 weeks.
Arm Title
Placebo QD and current Zolpidem therapy
Arm Type
Placebo Comparator
Arm Description
Zolpidem therapy will be reduced by dose, frequency, or both for up to 10 weeks.
Intervention Type
Drug
Intervention Name(s)
Ramelteon and zolpidem
Other Intervention Name(s)
Rozerem™, TAK-375, Ambien®
Intervention Description
Ramelteon 8 mg, tablets, orally, once daily and current zolpidem therapy incrementally reduced by dose, frequency, or both for up to 10 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo and zolpidem
Other Intervention Name(s)
Ambien®
Intervention Description
Ramelteon placebo-matching tablets, orally, once daily and current zolpidem therapy incrementally reduced by dose, frequency, or both for up to 10 weeks.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Discontinued Zolpidem Therapy
Description
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
Secondary Outcome Measure Information:
Title
Change From Baseline in Weekly Zolpidem Dosage During Weeks 1-2
Description
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
Title
Change From Baseline in Weekly Zolpidem Dosage During Weeks 3-4
Description
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
Title
Change From Baseline in Weekly Zolpidem Dosage During Weeks 5-6
Description
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
Title
Change From Baseline in Weekly Zolpidem Dosage During Weeks 7-8
Description
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
Title
Change From Baseline in Weekly Zolpidem Dosage During Weeks 9-10
Description
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
Title
Change From Baseline in Weekly Zolpidem Frequency During Weeks 1-2
Description
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
Title
Change From Baseline in Weekly Zolpidem Frequency During Weeks 3-4
Description
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
Title
Change From Baseline in Weekly Zolpidem Frequency During Weeks 5-6
Description
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
Title
Change From Baseline in Weekly Zolpidem Frequency During Weeks 7-8
Description
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
Title
Change From Baseline in Weekly Zolpidem Frequency During Weeks 9-10
Description
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
Title
Participants Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation
Description
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
Title
Participants Who Achieved a 50% Reduction in Zolpidem Dosage at the End of the Double-Blind Treatment Period
Description
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
Title
Participants Who Achieved a 50% Reduction in Zolpidem Dosage at Any Time During the Double-Blind Treatment Period
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director Clinical Science
Organizational Affiliation
Takeda Global Research & Development Center
Official's Role
Study Director
Facility Information:
City
Hot Springs
State/Province
Arkansas
Country
United States
City
Anaheim
State/Province
California
Country
United States
City
Fountain Valley
State/Province
California
Country
United States
City
La Mesa
State/Province
California
Country
United States
City
Los Angeles
State/Province
California
Country
United States
City
Redlands
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
San Francisco
State/Province
California
Country
United States
City
Santa Monica
State/Province
California
Country
United States
City
Denver
State/Province
Colorado
Country
United States
City
Clearwater
State/Province
Florida
Country
United States
City
Hollywood
State/Province
Florida
Country
United States
City
Kissimmee
State/Province
Florida
Country
United States
City
Naples
State/Province
Florida
Country
United States
City
Pembroke Pines
State/Province
Florida
Country
United States
City
Winter Park
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Austell
State/Province
Georgia
Country
United States
City
Boise
State/Province
Idaho
Country
United States
City
Louisville
State/Province
Kentucky
Country
United States
City
Metairie
State/Province
Louisiana
Country
United States
City
Chevy Chase
State/Province
Maryland
Country
United States
City
St. Louis
State/Province
Missouri
Country
United States
City
Lincoln
State/Province
Nebraska
Country
United States
City
New York
State/Province
New York
Country
United States
City
West Seneca
State/Province
New York
Country
United States
City
Raleigh
State/Province
North Carolina
Country
United States
City
Wilmington
State/Province
North Carolina
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Toledo
State/Province
Ohio
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Greer
State/Province
South Carolina
Country
United States
City
Fayetteville
State/Province
Tennessee
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Fort Worth
State/Province
Texas
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
San Angelo
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Salt Lake City
State/Province
Utah
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Facilitation of Zolpidem (≥10 mg) Discontinuation Through Use of Ramelteon in Subjects With Chronic Insomnia
We'll reach out to this number within 24 hrs