CClinicalTrials.gg
Sign In
CompletedNCT00492232Updated Jul 20, 2010Results posted

Facilitation of Zolpidem (≥10 mg) Discontinuation Through Use of Ramelteon in Subjects With Chronic Insomnia

A Phase 4 interventional study of Ramelteon and zolpidem and Placebo and zolpidem in Chronic Insomnia, sponsored by Takeda. Completed at 41 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2010-07-20.

Sponsored by Takeda · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
135
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Chronic Insomnia

Keywords

  • Chronic Insomnia
  • Sleep Initiation and Maintenance Disorder
  • Drug Therapy
03

In context

Sleep Initiation and Maintenance Disorders

1,856 studies on the registry are indexed under Sleep Initiation and Maintenance Disorders; 594 are open to participants now.

This study's enrollment of 135 is above the median of 73 across 1,631 interventional studies indexed under Sleep Initiation and Maintenance Disorders.

Browse Sleep Initiation and Maintenance Disorders studies →

Lead sponsor

Takeda is the lead sponsor of 1,002 studies on the registry; 92 are open to participants now.

Of its 173 completed or terminated interventional studies of FDA-regulated products, 149 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
135 participants (actual)

Study arms

  • Experimental
    Ramelteon 8 mg QD and current Zolpidem therapy

    Zolpidem therapy will be reduced by dose, frequency, or both for up to 10 weeks.

    Drug: Ramelteon and zolpidem

  • Placebo comparator
    Placebo QD and current Zolpidem therapy

    Zolpidem therapy will be reduced by dose, frequency, or both for up to 10 weeks.

    Drug: Placebo and zolpidem

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.

    Also known as: Rozerem™, TAK-375, Ambien®

  • 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.

    Also known as: Ambien®

06

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

07

Results

Posted Jul 17, 2009

Participant flow

Subjects were enrolled at 38 investigative sites in the United States from 26 April 2007 to 28 May 2008.

Placebo Run-in
Participant flow — Placebo Run-in
MilestoneRamelteon 8 mg QDPlacebo QD
Started0205
Completed0135
Not completed070
Withdrew: Adverse event02
Withdrew: Protocol violation03
Withdrew: Lost to follow-up03
Withdrew: Withdrawal by subject08
Withdrew: Pregnancy01
Withdrew: Entrance criteria not met045
Withdrew: Other06
Withdrew: Missing02
Double-Blind Treatment
Participant flow — Double-Blind Treatment
MilestoneRamelteon 8 mg QDPlacebo QD
Started6570
Completed4745
Not completed1825
Withdrew: Adverse event12
Withdrew: Protocol violation37
Withdrew: Lost to follow-up23
Withdrew: Withdrawal by subject48
Withdrew: Lack of efficacy10
Withdrew: Other65
Withdrew: Randomized not treated10
Open-Label Treatment
Participant flow — Open-Label Treatment
MilestoneRamelteon 8 mg QDPlacebo QD
Started890
Completed880
Not completed10
Withdrew: Withdrawal by subject10

Outcome measures

PrimaryPercentage 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
Reported as:
Number · Percentage of participants
Percentage of Participants Who Discontinued Zolpidem Therapy
Percentage of participantsRamelteon 8 mg QDPlacebo QD
Percentage of Participants Who Discontinued Zolpidem Therapy28.832.7
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · Regression, Logistic · p = 0.484 (Statistical significance was determined at the 0.05 level.) · Adjusted odds ratio: 0.71 · 95% CI 0.27 to 1.85Log odds of achieving response were estimated using the logistic regression analysis adjusted for effects of treatment and pooled center.
SecondaryChange 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
Reported as:
Least squares mean · Dose (mg)
Change From Baseline in Weekly Zolpidem Dosage During Weeks 1-2
Dose (mg)Ramelteon 8 mg QDPlacebo QD
Change From Baseline in Weekly Zolpidem Dosage During Weeks 1-2-11.8 ± 3.06-11.6 ± 3.11
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · ANCOVA · p = 0.946 (P-values are from t-tests of the analysis of covariance (ANCOVA) model for the difference in least squares (LS) means between treatments. Statistical significance was determined at the 0.05 level.) · Mean difference (final values): -0.2 · 95% CI -6.23 to 5.81LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs \>10 mg) and pooled center as covariates.
SecondaryChange 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
Reported as:
Least squares mean · Dose (mg)
Change From Baseline in Weekly Zolpidem Dosage During Weeks 3-4
Dose (mg)Ramelteon 8 mg QDPlacebo QD
Change From Baseline in Weekly Zolpidem Dosage During Weeks 3-4-35.3 ± 2.89-35.6 ± 2.93
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · ANCOVA · p = 0.901 (P-values are from t-tests of the ANCOVA model for the difference in LS means between treatments. Statistical significance was determined at the 0.05 level.) · Mean difference (final values): 0.4 · 95% CI -5.31 to 6.03LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs \>10 mg) and pooled center as covariates.
SecondaryChange 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
Reported as:
Least squares mean · Dose (mg)
Change From Baseline in Weekly Zolpidem Dosage During Weeks 5-6
Dose (mg)Ramelteon 8 mg QDPlacebo QD
Change From Baseline in Weekly Zolpidem Dosage During Weeks 5-6-40.2 ± 3.18-42.1 ± 3.22
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · ANCOVA · p = 0.538 (P-values are from t-tests of the ANCOVA model for the difference in LS means between treatments. Statistical significance was determined at the 0.05 level.) · Mean difference (final values): 2.0 · 95% CI -4.32 to 8.23LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs \>10 mg) and pooled center as covariates.
SecondaryChange 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
Reported as:
Least squares mean · Dose (mg)
Change From Baseline in Weekly Zolpidem Dosage During Weeks 7-8
Dose (mg)Ramelteon 8 mg QDPlacebo QD
Change From Baseline in Weekly Zolpidem Dosage During Weeks 7-8-52.1 ± 3.49-49.9 ± 3.49
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · ANCOVA · p = 0.517 (P-values are from t-tests of the ANCOVA model for the difference in LS means between treatments. Statistical significance was determined at the 0.05 level.) · Mean difference (final values): -2.2 · 95% CI -9.09 to 4.60LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs \>10 mg) and pooled center as covariates.
SecondaryChange 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
Reported as:
Least squares mean · Dose (mg)
Change From Baseline in Weekly Zolpidem Dosage During Weeks 9-10
Dose (mg)Ramelteon 8 mg QDPlacebo QD
Change From Baseline in Weekly Zolpidem Dosage During Weeks 9-10-60.6 ± 3.27-60.7 ± 3.31
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · ANCOVA · p = 0.965 (P-values are from t-tests of the ANCOVA model for the difference in LS means between treatments. Statistical significance was determined at the 0.05 level.) · Mean difference (final values): 0.1 · 95% CI -6.28 to 6.56LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs \>10 mg) and pooled center as covariates.
SecondaryChange 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
Reported as:
Least squares mean · nights per week
Change From Baseline in Weekly Zolpidem Frequency During Weeks 1-2
nights per weekRamelteon 8 mg QDPlacebo QD
Change From Baseline in Weekly Zolpidem Frequency During Weeks 1-20.13 ± 0.1830.04 ± 0.186
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · ANCOVA · p = 0.617 (P-values are from t-tests of the ANCOVA model for the difference in LS means between treatments. Statistical significance was determined at the 0.05 level.) · Mean difference (final values): 0.09 · 95% CI -0.27 to 0.45LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs \>10 mg), baseline zolpidem frequency, and pooled center as covariates.
SecondaryChange 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
Reported as:
Least squares mean · nights per week
Change From Baseline in Weekly Zolpidem Frequency During Weeks 3-4
nights per weekRamelteon 8 mg QDPlacebo QD
Change From Baseline in Weekly Zolpidem Frequency During Weeks 3-4-0.08 ± 0.288-0.26 ± 0.292
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · ANCOVA · p = 0.541 (P-values are from t-tests of the ANCOVA model for the difference in LS means between treatments. Statistical significance was determined at the 0.05 level.) · Mean difference (final values): 0.17 · 95% CI -0.39 to 0.74LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs \>10 mg), baseline zolpidem frequency, and pooled center as covariates.
SecondaryChange 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
Reported as:
Least squares mean · nights per week
Change From Baseline in Weekly Zolpidem Frequency During Weeks 5-6
nights per weekRamelteon 8 mg QDPlacebo QD
Change From Baseline in Weekly Zolpidem Frequency During Weeks 5-6-0.05 ± 0.396-0.60 ± 0.400
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · ANCOVA · p = 0.163 (P-values are from t-tests of the ANCOVA model for the difference in LS means between treatments. Statistical significance was determined at the 0.05 level.) · Mean difference (final values): 0.55 · 95% CI -0.23 to 1.33LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs \>10 mg), baseline zolpidem frequency, and pooled center as covariates.
SecondaryChange 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
Reported as:
Least squares mean · nights per week
Change From Baseline in Weekly Zolpidem Frequency During Weeks 7-8
nights per weekRamelteon 8 mg QDPlacebo QD
Change From Baseline in Weekly Zolpidem Frequency During Weeks 7-8-1.10 ± 0.475-1.24 ± 0.475
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · ANCOVA · p = 0.757 (P-values are from t-tests of the ANCOVA model for the difference in LS means between treatments. Statistical significance was determined at the 0.05 level.) · Mean difference (final values): 0.15 · 95% CI -0.79 to 1.08LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs \>10 mg), baseline zolpidem frequency, and pooled center as covariates.
SecondaryChange 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
Reported as:
Least squares mean · nights per week
Change From Baseline in Weekly Zolpidem Frequency During Weeks 9-10
nights per weekRamelteon 8 mg QDPlacebo QD
Change From Baseline in Weekly Zolpidem Frequency During Weeks 9-10-2.22 ± 0.534-2.34 ± 0.542
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · ANCOVA · p = 0.820 (P-values are from t-tests of the ANCOVA model for the difference in LS means between treatments. Statistical significance was determined at the 0.05 level.) · Mean difference (final values): 0.12 · 95% CI -0.93 to 1.17LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs \>10 mg), baseline zolpidem frequency, and pooled center as covariates.
SecondaryParticipants 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
Reported as:
Number · participants
Participants Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation
participantsRamelteon 8 mg QDPlacebo QD
Reduction in Dose128
Reduction in Dose and Frequency38
SecondaryParticipants 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
Reported as:
Number · participants
Participants Who Achieved a 50% Reduction in Zolpidem Dosage at the End of the Double-Blind Treatment Period
participantsRamelteon 8 mg QDPlacebo QD
Participants Who Achieved a 50% Reduction in Zolpidem Dosage at the End of the Double-Blind Treatment Period4842
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · Regression, Logistic · p = 0.284 (P-values are from Chi-square tests of the log-regression model for the overall treatment comparison. Statistical significance was determined at the 0.05 level.) · Adjusted odds ratio: 2.01 · 95% CI 0.55 to 7.34Log odds of achieving response were estimated using logistic regression analysis adjusted for effects of baseline zolpidem dosage (≤10 mg vs \>10 mg).
SecondaryParticipants 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
Reported as:
Number · participants
Participants Who Achieved a 50% Reduction in Zolpidem Dosage at Any Time During the Double-Blind Treatment Period
participantsRamelteon 8 mg QDPlacebo QD
Participants Who Achieved a 50% Reduction in Zolpidem Dosage at Any Time During the Double-Blind Treatment Period5050
Statistical analysis
  • Ramelteon 8 mg QD vs Placebo QD · Regression, Logistic · p = 0.389 (P-values are from Chi-square tests of the log-regression model for the overall treatment comparison. Statistical significance was determined at the 0.05 level.) · Adjusted odds ratio: 1.42 · 95% CI 0.64 to 3.13Log odds of achieving response were estimated using logistic regression analysis adjusted for effects of baseline zolpidem dosage (≤10 mg vs \>10 mg).

Adverse events

Collected over Treatment-emergent adverse events with onset dates the same or after the start of double-blind study medication and before the first dose of open-label study medication were summarized for the double-blind medication.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Ramelteon 8 mg QD—0/64 (0%)11/64 (17.2%)
Placebo QD—1/70 (1.4%)7/70 (10%)
Most frequent serious events
Most frequent serious events
EventRamelteon 8 mg QDPlacebo QD
Coronary Artery DiseaseCardiac disorders0/641/70
Most frequent other events
Most frequent other events
EventRamelteon 8 mg QDPlacebo QD
Upper Respiratory Tract InfectionsInfections and infestations5/642/70
DizzinessNervous system disorders4/641/70
HeadacheNervous system disorders2/644/70

Baseline characteristics

Age Continuous
Age Continuous(years)Ramelteon 8 mg QDPlacebo QDTotal
Mean51.5 ± 13.4547.0 ± 12.9849.2 ± 13.35
Sex: Female, Male
Sex: Female, Male(Participants)Ramelteon 8 mg QDPlacebo QDTotal
Female424991.0
Male232144.0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Subjects)Ramelteon 8 mg QDPlacebo QDTotal
Asian112.0
Black or African American5914.0
White5959118.0
Multiracial011.0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Ramelteon 8 mg QDPlacebo QDTotal
Hispanic or Latino10919.0
Not Hispanic or Latino5561116.0
Unknown or Not Reported000.0
Baseline average total daily zolpidem dosage
Baseline average total daily zolpidem dosage(subjects)Ramelteon 8 mg QDPlacebo QDTotal
≤10 mg5660116
>10 mg81018
Information not available101
Use of pharmacological assistance to sleep
Use of pharmacological assistance to sleep(subjects)Ramelteon 8 mg QDPlacebo QDTotal
4 nights per week8917
>4 nights per week5761118
Weekly frequency zolpidem consumption
Weekly frequency zolpidem consumption(subjects)Ramelteon 8 mg QDPlacebo QDTotal
0-3 nights per week000
4 nights per week213
5 nights per week8917
6 nights per week8715
7 nights per week465399
Information not available101
Baseline weekly zolpidem dosage
Baseline weekly zolpidem dosage(Dosage (mg))Ramelteon 8 mg QDPlacebo QDTotal
Mean68.7 ± 17.7170.3 ± 20.3769.5 ± 19.09

1 further baseline measures are reported on the registry.

08

Study locations

41 sites
  • Hot Springs, Arkansas, United States
  • Anaheim, California, United States
  • Fountain Valley, California, United States
  • La Mesa, California, United States
  • Los Angeles, California, United States
  • Redlands, California, United States
  • San Diego, California, United States
  • San Francisco, California, United States
  • Santa Monica, California, United States
  • Denver, Colorado, United States
  • Clearwater, Florida, United States
  • Hollywood, Florida, United States
  • Kissimmee, Florida, United States
  • Naples, Florida, United States
  • Pembroke Pines, Florida, United States
  • Winter Park, Florida, United States
  • Atlanta, Georgia, United States
  • Austell, Georgia, United States
  • Boise, Idaho, United States
  • Louisville, Kentucky, United States
  • Metairie, Louisiana, United States
  • Chevy Chase, Maryland, United States
  • St. Louis, Missouri, United States
  • Lincoln, Nebraska, United States
  • New York, New York, United States
  • West Seneca, New York, United States
  • Raleigh, North Carolina, United States
  • Wilmington, North Carolina, United States
  • Cincinnati, Ohio, United States
  • Toledo, Ohio, United States
  • Portland, Oregon, United States
  • Philadelphia, Pennsylvania, United States
  • Greer, South Carolina, United States
  • Fayetteville, Tennessee, United States
  • Austin, Texas, United States
  • Dallas, Texas, United States
  • Fort Worth, Texas, United States
  • Houston, Texas, United States
  • San Angelo, Texas, United States
  • San Antonio, Texas, United States
  • Salt Lake City, Utah, United States
09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 20, 2010, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00492232
Lead sponsor
Takeda
First posted
Jun 27, 2007
Start date
Apr 2007
Primary completion
Mar 2008
Completion
May 2008
Results posted
Jul 17, 2009
Last update
Jul 20, 2010

Study contacts

Medical Director Clinical Science
study director · Takeda Global Research & Development Center

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2010. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Sleep Initiation and Maintenance Disorders→

Other studies from this sponsor

Takeda

Start the discussion