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Trial record 5 of 133 for:    ZOLPIDEM

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

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ClinicalTrials.gov Identifier: NCT00492232
Recruitment Status : Completed
First Posted : June 27, 2007
Results First Posted : July 17, 2009
Last Update Posted : July 20, 2010
Sponsor:
Information provided by:
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Chronic Insomnia
Interventions Drug: Ramelteon and zolpidem
Drug: Placebo and zolpidem
Enrollment 135
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.
Arm/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP. Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Period Title: Placebo Run-in
Started 0 205 [1]
Completed 0 135 [2]
Not Completed 0 70
Reason Not Completed
Adverse Event             0             2
Protocol Violation             0             3
Lost to Follow-up             0             3
Withdrawal by Subject             0             8
Pregnancy             0             1
Entrance criteria not met             0             45
Other             0             6
Missing             0             2
[1]
All subjects received placebo in the placebo run-in period.
[2]
These subjects successfully completed the placebo run-in period and were randomized to the DBTP.
Period Title: Double-Blind Treatment
Started 65 70
Completed 47 45
Not Completed 18 25
Reason Not Completed
Adverse Event             1             2
Protocol Violation             3             7
Lost to Follow-up             2             3
Withdrawal by Subject             4             8
Lack of Efficacy             1             0
Other             6             5
Randomized not treated             1             0
Period Title: Open-Label Treatment
Started 89 [1] 0 [2]
Completed 88 0
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
[1]
In the previous DBTP, 45 and 44 subjects were randomized to ramelteon and placebo, respectively.
[2]
All subjects received ramelteon in the OLTP.
Arm/Group Title Ramelteon 8 mg QD Placebo QD Total
Hide Arm/Group Description Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP. Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP. Total of all reporting groups
Overall Number of Baseline Participants 65 70 135
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 65 participants 70 participants 135 participants
51.5  (13.45) 47.0  (12.98) 49.2  (13.35)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 70 participants 135 participants
Female
42
  64.6%
49
  70.0%
91.0
Male
23
  35.4%
21
  30.0%
44.0
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 65 participants 70 participants 135 participants
Asian 1 1 2
Black or African American 5 9 14
White 59 59 118
Multiracial 0 1 1
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 70 participants 135 participants
Hispanic or Latino
10
  15.4%
9
  12.9%
19.0
Not Hispanic or Latino
55
  84.6%
61
  87.1%
116.0
Unknown or Not Reported
0
   0.0%
0
   0.0%
0.0
Baseline average total daily zolpidem dosage  
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 65 participants 70 participants 135 participants
≤10 mg 56 60 116
>10 mg 8 10 18
Information not available 1 0 1
Use of pharmacological assistance to sleep   [1] 
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 65 participants 70 participants 135 participants
4 nights per week 8 9 17
>4 nights per week 57 61 118
[1]
Measure Description: Randomized subjects responded to the question, "How often per week do you use pharmacological assistance to sleep?" 4=4 nights/week; >4=5-7 nights/week.
Weekly frequency zolpidem consumption   [1] 
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 65 participants 70 participants 135 participants
0-3 nights per week 0 0 0
4 nights per week 2 1 3
5 nights per week 8 9 17
6 nights per week 8 7 15
7 nights per week 46 53 99
Information not available 1 0 1
[1]
Measure Description: The average number of nights per week subjects took zolpidem was calculated.
Baseline weekly zolpidem dosage   [1] 
Mean (Standard Deviation)
Unit of measure:  Dosage (mg)
Number Analyzed 65 participants 70 participants 135 participants
68.7  (17.71) 70.3  (20.37) 69.5  (19.09)
[1]
Measure Description: Baseline for the weekly zolpidem dosage was calculated as the total amount zolpidem intake recorded by a subject during placebo run-in, divided by the number of days in the period, multiplied by 7. Ramelteon 8 mg n=64; Placebo n=70.
Weekly frequency zolpidem consumption   [1] 
Mean (Standard Deviation)
Unit of measure:  Nights per week
Number Analyzed 65 participants 70 participants 135 participants
6.53  (0.835) 6.60  (0.769) 6.57  (0.799)
[1]
Measure Description: Average number of nights per week randomized subjects used zolpidem. Ramelteon 8 mg n=64; Placebo n=70.
1.Primary Outcome
Title Percentage of Participants Who Discontinued Zolpidem Therapy
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 49
Measure Type: Number
Unit of Measure: Percentage of participants
28.8 32.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.484
Comments Statistical significance was determined at the 0.05 level.
Method Regression, Logistic
Comments Log odds of achieving response were estimated using the logistic regression analysis adjusted for effects of treatment and pooled center.
Method of Estimation Estimation Parameter Adjusted Odds Ratio
Estimated Value 0.71
Confidence Interval 95%
0.27 to 1.85
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Weekly Zolpidem Dosage During Weeks 1-2
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 49
Least Squares Mean (Standard Error)
Unit of Measure: Dose (mg)
-11.8  (3.06) -11.6  (3.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.946
Comments 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.
Method ANCOVA
Comments LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs >10 mg) and pooled center as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval 95%
-6.23 to 5.81
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Weekly Zolpidem Dosage During Weeks 3-4
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 49
Least Squares Mean (Standard Error)
Unit of Measure: Dose (mg)
-35.3  (2.89) -35.6  (2.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.901
Comments 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.
Method ANCOVA
Comments LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs >10 mg) and pooled center as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval 95%
-5.31 to 6.03
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Weekly Zolpidem Dosage During Weeks 5-6
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 48
Least Squares Mean (Standard Error)
Unit of Measure: Dose (mg)
-40.2  (3.18) -42.1  (3.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.538
Comments 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.
Method ANCOVA
Comments LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs >10 mg) and pooled center as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.0
Confidence Interval 95%
-4.32 to 8.23
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Weekly Zolpidem Dosage During Weeks 7-8
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 51 48
Least Squares Mean (Standard Error)
Unit of Measure: Dose (mg)
-52.1  (3.49) -49.9  (3.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.517
Comments 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.
Method ANCOVA
Comments LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs >10 mg) and pooled center as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.2
Confidence Interval 95%
-9.09 to 4.60
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Weekly Zolpidem Dosage During Weeks 9-10
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 49
Least Squares Mean (Standard Error)
Unit of Measure: Dose (mg)
-60.6  (3.27) -60.7  (3.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.965
Comments 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.
Method ANCOVA
Comments LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs >10 mg) and pooled center as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval 95%
-6.28 to 6.56
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Weekly Zolpidem Frequency During Weeks 1-2
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 49
Least Squares Mean (Standard Error)
Unit of Measure: nights per week
0.13  (0.183) 0.04  (0.186)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.617
Comments 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.
Method ANCOVA
Comments LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs >10 mg), baseline zolpidem frequency, and pooled center as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.09
Confidence Interval 95%
-0.27 to 0.45
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Weekly Zolpidem Frequency During Weeks 3-4
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 49
Least Squares Mean (Standard Error)
Unit of Measure: nights per week
-0.08  (0.288) -0.26  (0.292)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.541
Comments 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.
Method ANCOVA
Comments LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs >10 mg), baseline zolpidem frequency, and pooled center as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.17
Confidence Interval 95%
-0.39 to 0.74
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Weekly Zolpidem Frequency During Weeks 5-6
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 48
Least Squares Mean (Standard Error)
Unit of Measure: nights per week
-0.05  (0.396) -0.60  (0.400)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.163
Comments 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.
Method ANCOVA
Comments LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs >10 mg), baseline zolpidem frequency, and pooled center as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.55
Confidence Interval 95%
-0.23 to 1.33
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Weekly Zolpidem Frequency During Weeks 7-8
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 51 48
Least Squares Mean (Standard Error)
Unit of Measure: nights per week
-1.10  (0.475) -1.24  (0.475)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.757
Comments 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.
Method ANCOVA
Comments LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs >10 mg), baseline zolpidem frequency, and pooled center as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.15
Confidence Interval 95%
-0.79 to 1.08
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Weekly Zolpidem Frequency During Weeks 9-10
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 49
Least Squares Mean (Standard Error)
Unit of Measure: nights per week
-2.22  (0.534) -2.34  (0.542)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.820
Comments 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.
Method ANCOVA
Comments LS means are from an ANCOVA model with baseline zolpidem dosage (≤10 mg vs >10 mg), baseline zolpidem frequency, and pooled center as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.12
Confidence Interval 95%
-0.93 to 1.17
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Participants Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 49
Measure Type: Number
Unit of Measure: participants
Reduction in Dose 12 8
Reduction in Dose and Frequency 3 8
13.Secondary Outcome
Title Participants Who Achieved a 50% Reduction in Zolpidem Dosage at the End of the Double-Blind Treatment Period
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 52 49
Measure Type: Number
Unit of Measure: participants
48 42
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.284
Comments 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.
Method Regression, Logistic
Comments Log odds of achieving response were estimated using logistic regression analysis adjusted for effects of baseline zolpidem dosage (≤10 mg vs >10 mg).
Method of Estimation Estimation Parameter Adjusted Odds Ratio
Estimated Value 2.01
Confidence Interval 95%
0.55 to 7.34
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Participants Who Achieved a 50% Reduction in Zolpidem Dosage at Any Time During the Double-Blind Treatment Period
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description:
Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP.
Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
Overall Number of Participants Analyzed 64 70
Measure Type: Number
Unit of Measure: participants
50 50
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramelteon 8 mg QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.389
Comments 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.
Method Regression, Logistic
Comments Log odds of achieving response were estimated using logistic regression analysis adjusted for effects of baseline zolpidem dosage (≤10 mg vs >10 mg).
Method of Estimation Estimation Parameter Adjusted Odds Ratio
Estimated Value 1.42
Confidence Interval 95%
0.64 to 3.13
Estimation Comments [Not Specified]
Time Frame 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.
Adverse Event Reporting Description Two ramelteon-treated subjects permanently discontinued the study due to adverse events during the double-blind treatment period. One placebo-treated subject had multiple temporary study drug interruptions due to adverse events but did not permanently discontinue the study
 
Arm/Group Title Ramelteon 8 mg QD Placebo QD
Hide Arm/Group Description Ramelteon 8 mg, tablets, orally, once daily for up to 10 weeks in the DBTP. Ramelteon placebo-matching tablets, orally, once daily for up to 10 weeks in the DBTP.
All-Cause Mortality
Ramelteon 8 mg QD Placebo QD
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Ramelteon 8 mg QD Placebo QD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/64 (0.00%)      1/70 (1.43%)    
Cardiac disorders     
Coronary Artery Disease  1  0/64 (0.00%)  0 1/70 (1.43%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ramelteon 8 mg QD Placebo QD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/64 (17.19%)      7/70 (10.00%)    
Infections and infestations     
Upper Respiratory Tract Infections  1  5/64 (7.81%)  5 2/70 (2.86%)  2
Nervous system disorders     
Dizziness  1  4/64 (6.25%)  5 1/70 (1.43%)  1
Headache  1  2/64 (3.13%)  2 4/70 (5.71%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period up to 150 days to permit actions necessary to preserve sponsor's intellectual property; can request changes to the results communication only for the purpose of removing non study related information that is proprietary and confidential to sponsor; can require delay of a results communication until the study has been completed at all participating sites.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
Phone: 800-778-2860
EMail: clinicaltrialregistry@tpna.com
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Responsible Party: Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00492232     History of Changes
Other Study ID Numbers: 01-06-TL-375-071
U1111-1114-3262 ( Registry Identifier: WHO )
First Submitted: June 25, 2007
First Posted: June 27, 2007
Results First Submitted: May 28, 2009
Results First Posted: July 17, 2009
Last Update Posted: July 20, 2010