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Study of the Safety and Effectiveness of Esmirtazapine in Participants With Chronic Primary Insomnia (P05706) (RUBY)

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ClinicalTrials.gov Identifier: NCT00482612
Recruitment Status : Completed
First Posted : June 5, 2007
Results First Posted : July 10, 2014
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Insomnia
Interventions Drug: Esmirtazapine
Drug: Placebo
Enrollment 526
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Esmirtazapine 1.5 mg Esmirtazapine 3.0 mg Esmirtazapine 4.5 mg Placebo
Hide Arm/Group Description Participants took esmirtazapine 1.5 mg tablets once daily by mouth during the 14-day In-treatment Period. Participants were followed for safety during a Follow-up Period, in which no study medication was administered. Participants took esmirtazapine 3.0 mg tablets once daily by mouth during the 14-day In-treatment Period. Participants were followed for safety during a Follow-up Period, in which no study medication was administered. Participants took esmirtazapine 4.5 mg tablets once daily by mouth during the 14-day In-treatment Period. Participants were followed for safety during a Follow-up Period, in which no study medication was administered. Participants took placebo tablets once daily by mouth during the 14-day In-treatment Period. Participants were followed for safety during a Follow-up Period, in which no study medication was administered.
Period Title: In-treatment Period
Started 137 125 129 135
Treated 137 125 128 135
Completed 137 125 128 135
Not Completed 0 0 1 0
Reason Not Completed
No study medication administered             0             0             1             0
Period Title: Follow-up Period
Started 137 125 128 135
Completed 123 107 106 127
Not Completed 14 18 22 8
Reason Not Completed
Other             4             2             1             2
Lack of compliance             0             0             1             0
Lost to Follow-up             0             4             2             1
Adverse Event             4             7             9             0
Lack of Efficacy             2             0             1             0
Withdrawal by Subject             3             5             7             2
Reasons not related to trial             1             0             1             3
Arm/Group Title Esmirtazapine 1.5 mg Esmirtazapine 3.0 mg Esmirtazapine 4.5 mg Placebo Total
Hide Arm/Group Description Participants took esmirtazapine 1.5 mg tablets once daily by mouth during the 14-day In-treatment Period. No study medication was administered during the Follow-up Period. Participants took esmirtazapine 3.0 mg tablets once daily by mouth during the 14-day In-treatment Period. No study medication was administered during the Follow-up Period. Participants took esmirtazapine 4.5 mg tablets once daily by mouth during the 14-day In-treatment Period. No study medication was administered during the Follow-up Period. Participants took placebo tablets once daily by mouth during the 14-day In-treatment Period. No study medication was administered during the Follow-up Period. Total of all reporting groups
Overall Number of Baseline Participants 137 125 128 135 525
Hide Baseline Analysis Population Description
Baseline characteristics were reported for the All-Subjects-Treated group. One participant who was randomized to receive MK-8265 4.5 mg did not receive double-blind study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 137 participants 125 participants 128 participants 135 participants 525 participants
44.8  (12.4) 45.6  (12.0) 44.5  (12.2) 46.2  (11.3) 45.3  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 137 participants 125 participants 128 participants 135 participants 525 participants
Female
92
  67.2%
85
  68.0%
72
  56.3%
90
  66.7%
339
  64.6%
Male
45
  32.8%
40
  32.0%
56
  43.8%
45
  33.3%
186
  35.4%
1.Primary Outcome
Title Average Total Sleep Time (TST) as Recorded Daily in the Sleep Diary During the 14-day In-treatment Period
Hide Description TST was defined as the total amount of time (measured in minutes) that was actually spent sleeping the previous night as recorded daily in the participant's sleep diary. TST values over the 14-day active treatment period were averaged for each participant, and average TST was then reported by treatment arm. For participants with missing data, the average of the nights for which TST data were present was used in the analysis.
Time Frame Day 1 to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat Group consisted of all randomized participants who received at least one dose of double-blind trial medication, and had baseline and at least one post-baseline measurement for at least one efficacy assessment.
Arm/Group Title Esmirtazapine 1.5 mg Esmirtazapine 3.0 mg Esmirtazapine 4.5 mg Placebo
Hide Arm/Group Description:
Participants took esmirtazapine 1.5 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took esmirtazapine 3.0 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took esmirtazapine 4.5 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took placebo tablets once daily by mouth during the 14-day In-treatment Period.
Overall Number of Participants Analyzed 135 121 126 133
Mean (Standard Deviation)
Unit of Measure: Minutes
382.14  (68.155) 382.77  (81.172) 394.83  (85.575) 351.40  (78.551)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Esmirtazapine 1.5 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Baseline TST was used as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Esmirtazapine 3.0 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Baseline TST was used as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Esmirtazapine 4.5 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Baseline TST was used as a covariate.
2.Secondary Outcome
Title Average Sleep Latency (SL) as Recorded Daily in the Sleep Diary During the 14-day In-treatment Period
Hide Description SL was defined as the duration of time measured in minutes that it took a participant to fall asleep as recorded daily in the participant's sleep diary. SL values over the 14-day active treatment period were averaged for each participant, and average SL was then reported by treatment arm. For participants with missing data, the average of the nights for which TST data were present were used in the analysis.
Time Frame Day 1 to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat Group consisted of all randomized participants who received at least one dose of double-blind trial medication and had baseline and at least one post-baseline measurement for at least one efficacy assessment.
Arm/Group Title Esmirtazapine 1.5 mg Esmirtazapine 3.0 mg Esmirtazapine 4.5 mg Placebo
Hide Arm/Group Description:
Participants took esmirtazapine 1.5 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took esmirtazapine 3.0 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took esmirtazapine 4.5 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took placebo tablets once daily by mouth during the 14-day In-treatment Period.
Overall Number of Participants Analyzed 135 121 126 133
Mean (Standard Deviation)
Unit of Measure: Minutes
48.93  (34.59) 52.02  (38.95) 50.80  (45.76) 60.13  (42.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Esmirtazapine 1.5 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method ANCOVA
Comments Baseline SL was used as a covariate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Esmirtazapine 3.0 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0135
Comments [Not Specified]
Method ANCOVA
Comments Baseline SL was used as a covariate.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Esmirtazapine 4.5 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Baseline SL was used as a covariate.
3.Secondary Outcome
Title Number of Participants Experiencing an Adverse Event (AE) During the 14-day In-treatment Period
Hide Description The total number of participants with an AE during the 14-day In-treatment Period was tallied for each treatment arm. An AE was defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time Frame Day 1 to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The All-Subjects-Treated Group consisted of all participants who received at least 1 dose of trial medication.
Arm/Group Title Esmirtazapine 1.5 mg Esmirtazapine 3.0 mg Esmirtazapine 4.5 mg Placebo
Hide Arm/Group Description:
Participants took esmirtazapine 1.5 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took esmirtazapine 3.0 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took esmirtazapine 4.5 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took placebo tablets once daily by mouth during the 14-day In-treatment Period.
Overall Number of Participants Analyzed 137 125 128 135
Measure Type: Number
Unit of Measure: Number of participants
35 41 41 28
4.Secondary Outcome
Title Number of Participants Who Discontinued From Study Treatment Due to an AE During the 14-day In-Treatment Period
Hide Description The total number of participants discontinuing from study treatment due to experiencing an AE was tallied for each treatment arm. An AE was defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time Frame Day 1 to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The All-Subjects-Treated Group consisted of all participants who received at least 1 dose of trial medication.
Arm/Group Title Esmirtazapine 1.5 mg Esmirtazapine 3.0 mg Esmirtazapine 4.5 mg Placebo
Hide Arm/Group Description:
Participants took esmirtazapine 1.5 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took esmirtazapine 3.0 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took esmirtazapine 4.5 mg tablets once daily by mouth during the 14-day In-treatment Period.
Participants took placebo tablets once daily by mouth during the 14-day In-treatment Period.
Overall Number of Participants Analyzed 137 125 128 135
Measure Type: Number
Unit of Measure: Number of participants
4 7 9 0
Time Frame From Day 1 of the Treatment Period up to 30 days after completion of the Treatment Period (up to 45 days). AE data were not reported for the 1 enrolled participant who did not receive study medication.
Adverse Event Reporting Description AEs were collected for 525 treated participants separately during the In-Treatment Period (Days 1-15) and during the Follow-up Period (up to Day 45).
 
Arm/Group Title Esmirtazapine 1.5 mg In-treatment Esmirtazapine 3.0 mg In-Treatment Esmirtazapine 4.5 mg In-treatment Placebo In-treatment Esmirtazapine 1.5 mg Follow-up Esmirtazapine 3.0 mg Folow-up Esmirtazapine 4.5 mg Follow-up Placebo Follow-up
Hide Arm/Group Description Participants took esmirtazapine 1.5 mg tablets once daily by mouth during the 14-day In-treatment Period. Participants took esmirtazapine 3.0 mg tablets once daily by mouth during the 14-day In-treatment Period. Participants took esmirtazapine 4.5 mg tablets once daily by mouth during the 14-day In-treatment Period. Participants took placebo tablets once daily by mouth during the 14-day In-treatment Period. After receiving 1.5 mg esmirtazipine in the In-Treatment Period, participants were followed for safety during a Follow-up Period in which no study medication was administered. After receiving 3.0 mg esmirtazipine in the In-Treatment Period, participants were followed for safety during a Follow-up Period in which no study medication was administered. After receiving 4.5 mg esmirtazipine in the In-Treatment Period, participants were followed for safety during a Follow-up Period in which no study medication was administered. After receiving placebo in the In-Treatment Period, participants were followed for safety during a Follow-up Period in which no study medication was administered.
All-Cause Mortality
Esmirtazapine 1.5 mg In-treatment Esmirtazapine 3.0 mg In-Treatment Esmirtazapine 4.5 mg In-treatment Placebo In-treatment Esmirtazapine 1.5 mg Follow-up Esmirtazapine 3.0 mg Folow-up Esmirtazapine 4.5 mg Follow-up Placebo Follow-up
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Esmirtazapine 1.5 mg In-treatment Esmirtazapine 3.0 mg In-Treatment Esmirtazapine 4.5 mg In-treatment Placebo In-treatment Esmirtazapine 1.5 mg Follow-up Esmirtazapine 3.0 mg Folow-up Esmirtazapine 4.5 mg Follow-up Placebo Follow-up
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/137 (1.46%)      1/125 (0.80%)      1/128 (0.78%)      0/135 (0.00%)      0/137 (0.00%)      0/125 (0.00%)      0/128 (0.00%)      0/135 (0.00%)    
Infections and infestations                 
Appendicitis  1  0/137 (0.00%)  0 0/125 (0.00%)  0 1/128 (0.78%)  1 0/135 (0.00%)  0 0/137 (0.00%)  0 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0
Bronchitis  1  1/137 (0.73%)  1 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0 0/137 (0.00%)  0 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0
Staphylococcal infection  1  1/137 (0.73%)  1 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0 0/137 (0.00%)  0 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                 
Acute respiratory failure  1  1/137 (0.73%)  1 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0 0/137 (0.00%)  0 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0
Asthma  1  1/137 (0.73%)  1 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0 0/137 (0.00%)  0 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0
Surgical and medical procedures                 
Abdominoplasty  1  0/137 (0.00%)  0 1/125 (0.80%)  1 0/128 (0.00%)  0 0/135 (0.00%)  0 0/137 (0.00%)  0 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v.11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Esmirtazapine 1.5 mg In-treatment Esmirtazapine 3.0 mg In-Treatment Esmirtazapine 4.5 mg In-treatment Placebo In-treatment Esmirtazapine 1.5 mg Follow-up Esmirtazapine 3.0 mg Folow-up Esmirtazapine 4.5 mg Follow-up Placebo Follow-up
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/137 (7.30%)      11/125 (8.80%)      9/128 (7.03%)      2/135 (1.48%)      0/137 (0.00%)      0/125 (0.00%)      0/128 (0.00%)      0/135 (0.00%)    
Nervous system disorders                 
Somnolence  1  10/137 (7.30%)  10 11/125 (8.80%)  11 9/128 (7.03%)  9 2/135 (1.48%)  2 0/137 (0.00%)  0 0/125 (0.00%)  0 0/128 (0.00%)  0 0/135 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v.11.0
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.
All publications must be based on data validated and released by the Sponsor. Any such scientific paper, presentation, or other communication concerning the clinical trial will first be submitted to the Sponsor, at least 6 weeks ahead of estimated publication or presentation, for written consent, which shall not be withheld unreasonably.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00482612     History of Changes
Other Study ID Numbers: P05706
176001 ( Other Identifier: Protocol number )
MK-8265-003 ( Other Identifier: Protocol number )
First Submitted: June 1, 2007
First Posted: June 5, 2007
Results First Submitted: June 9, 2014
Results First Posted: July 10, 2014
Last Update Posted: October 3, 2018