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Phase IIB 2-Period Crossover Polysomnography Study in Participants With Primary Insomnia (MK-4305-006)

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ClinicalTrials.gov Identifier: NCT00792298
Recruitment Status : Completed
First Posted : November 17, 2008
Results First Posted : November 14, 2014
Last Update Posted : November 6, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Primary Insomnia
Interventions Drug: Suvorexant
Drug: Dose-matched Placebo to Suvorexant
Enrollment 254
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Suvorexant 10 mg → Placebo Placebo → Suvorexant 10 mg Suvorexant 20 mg → Placebo Placebo → Suvorexant 20 mg Suvorexant 40 mg → Placebo Placebo → Suvorexant 40 mg Suvorexant 80 mg → Placebo Placebo → Suvorexant 80 mg
Hide Arm/Group Description After an ~1- to 2-week single-blind placebo run-in period, participants received 10 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2. After an ~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 10 mg suvorexant daily prior to bedtime during Treatment Period 2. After an ~1- to 2-week single-blind placebo run-in period, participants received 20 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2. After an ~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 20 mg suvorexant daily prior to bedtime during Treatment Period 2. After an ~1- to 2-week single-blind placebo run-in period, participants received 40 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2. After an ~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 40 mg suvorexant daily prior to bedtime during Treatment Period 2. After an ~1- to 2-week single-blind placebo run-in period, participants received 80 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2. After an ~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 80 mg suvorexant daily prior to bedtime during Treatment Period 2.
Period Title: Treatment Period 1
Started 31 32 33 32 32 32 31 31
Completed 30 31 31 28 32 29 27 30
Not Completed 1 1 2 4 0 3 4 1
Reason Not Completed
Adverse Event             0             1             0             1             0             1             1             0
Lack of Efficacy             0             0             1             0             0             0             0             0
Withdrawal by Subject             1             0             1             2             0             2             1             0
Lost to Follow-up             0             0             0             0             0             0             1             0
Physician Decision             0             0             0             1             0             0             1             0
Protocol Violation             0             0             0             0             0             0             0             1
Period Title: Washout
Started 30 31 32 [1] 28 32 29 29 [2] 30
Completed 30 31 31 28 32 27 29 30
Not Completed 0 0 1 0 0 2 0 0
Reason Not Completed
Adverse Event             0             0             0             0             0             1             0             0
Withdrawal by Subject             0             0             1             0             0             1             0             0
[1]
1 participant discontinued therapy during Period 1 but entered the Washout as allowed per protocol
[2]
2 participants discontinued therapy during Period 1 but entered the Washout as allowed per protocol
Period Title: Treatment Period 2
Started 30 31 31 28 32 27 29 30
Completed 29 30 30 26 30 27 28 28
Not Completed 1 1 1 2 2 0 1 2
Reason Not Completed
Lack of Efficacy             0             0             0             0             1             0             0             0
Physician Decision             0             0             0             0             0             0             1             0
Pregnancy             0             0             1             0             0             0             0             0
Withdrawal by Subject             1             1             0             2             1             0             0             2
Arm/Group Title All Treated Participants
Hide Arm/Group Description All randomized participants who received at least one dose of study treatment.
Overall Number of Baseline Participants 254
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 254 participants
44.4  (11.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 254 participants
Female
148
  58.3%
Male
106
  41.7%
1.Primary Outcome
Title LS Mean Sleep Efficiency (SE) During Periods 1 and 2
Hide Description SE was defined as total sleep time (TST) in minutes divided by time in bed (measured from lights off to lights on; fixed at 8 hours on each Polysomnography [PSG] night) in minutes, multiplied by 100, where TST is defined as the total time (minutes) in Stages 1, 2, 3, 4 and Rapid Eye Movement (REM). SE= (total sleep time/time in bed) x 100
Time Frame Night 1 and end of Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
Arm/Group Title Placebo Suvorexant 10 mg Suvorexant 20 mg Suvorexant 40 mg Suvorexant 80 mg
Hide Arm/Group Description:
Participants received dose-matched placebo to suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 10 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 20 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 40 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 80 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Overall Number of Participants Analyzed 249 62 61 59 61
Least Squares Mean (Standard Error)
Unit of Measure: percent of time in bed
Night 1 (n=249, 62, 61, 59, 61) 75.8  (0.93) 81.0  (1.75) 83.4  (1.75) 86.6  (1.77) 88.7  (1.77)
Week 4 (n=232, 59, 57, 57, 55) 76.6  (0.94) 81.3  (1.66) 87.0  (1.68) 84.4  (1.68) 84.2  (1.70)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 80 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value 12.9
Confidence Interval (2-Sided) 95%
9.5 to 16.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 80 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value 7.6
Confidence Interval (2-Sided) 95%
4.4 to 10.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 40 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value 10.8
Confidence Interval (2-Sided) 95%
7.4 to 14.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 40 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value 7.8
Confidence Interval (2-Sided) 95%
4.6 to 10.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 20 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value 7.6
Confidence Interval (2-Sided) 95%
4.2 to 11.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 20 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value 10.4
Confidence Interval (2-Sided) 95%
7.2 to 13.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 10 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value 5.2
Confidence Interval (2-Sided) 95%
1.9 to 8.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 20 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
1.6 to 7.8
Estimation Comments [Not Specified]
2.Secondary Outcome
Title LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2
Hide Description WASO was defined as the duration of wakefulness measured in minutes (any epoch of Stage 0) from persistent sleep onset (first epoch of the first twenty consecutive epochs of non-wake) to lights on.
Time Frame Night 1 and end of Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
Arm/Group Title Placebo Suvorexant 10 mg Suvorexant 20 mg Suvorexant 40 mg Suvorexant 80 mg
Hide Arm/Group Description:
Participants received dose-matched placebo to suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 10 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 20 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 40 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 80 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Overall Number of Participants Analyzed 249 62 61 59 61
Least Squares Mean (Standard Error)
Unit of Measure: minutes
Night 1 (n=249, 62, 61, 59, 61) 72.4  (3.38) 51.3  (6.40) 47.7  (6.41) 38.5  (6.47) 35.6  (6.46)
Week 4 (n=232, 59, 57, 57, 55) 76.7  (3.60) 55.2  (6.65) 48.6  (6.75) 43.4  (6.77) 47.8  (6.84)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 80 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -36.8
Confidence Interval (2-Sided) 95%
-49.4 to -24.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 80 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -28.9
Confidence Interval (2-Sided) 95%
-42.1 to -15.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 40 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -33.9
Confidence Interval (2-Sided) 95%
-46.4 to -21.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 40 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -33.2
Confidence Interval (2-Sided) 95%
-46.3 to -20.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 20 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -24.7
Confidence Interval (2-Sided) 95%
-37.1 to -12.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 20 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -28.1
Confidence Interval (2-Sided) 95%
-41.0 to -15.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 10 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -21.2
Confidence Interval (2-Sided) 95%
-33.5 to -8.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 10 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -21.4
Confidence Interval (2-Sided) 95%
-34.2 to -8.7
Estimation Comments [Not Specified]
3.Secondary Outcome
Title LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2
Hide Description LPS is defined as the duration of time measured in minutes from lights off to persistent sleep onset.
Time Frame Night 1 and end of Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
Arm/Group Title Placebo Suvorexant 10 mg Suvorexant 20 mg Suvorexant 40 mg Suvorexant 80 mg
Hide Arm/Group Description:
Participants received dose-matched placebo to suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 10 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 20 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 40 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Participants received 80 mg suvorexant daily prior to bedtime over a 4-week treatment period.
Overall Number of Participants Analyzed 249 62 61 59 61
Least Squares Mean (Standard Error)
Unit of Measure: minutes
Night 1 (n=249, 62, 61, 59, 61) 49.8  (2.91) 46.4  (6.08) 40.4  (6.08) 26.7  (6.13) 24.4  (6.13)
Week 4 (n=232, 59, 57, 57, 55) 41.7  (2.75) 39.4  (5.12) 19.4  (5.17) 37.9  (5.19) 32.2  (5.28)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 80 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -25.4
Confidence Interval (2-Sided) 95%
-37.7 to -13.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 80 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.068
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -9.5
Confidence Interval (2-Sided) 95%
-19.7 to 0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 40 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -23.1
Confidence Interval (2-Sided) 95%
-35.3 to -10.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 40 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.459
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-13.8 to 6.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 20 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.130
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -9.4
Confidence Interval (2-Sided) 95%
-21.5 to 2.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 20 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -22.3
Confidence Interval (2-Sided) 95%
-32.3 to -12.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 10 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.577
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -3.4
Confidence Interval (2-Sided) 95%
-15.6 to 8.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 10 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.644
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-12.2 to 7.5
Estimation Comments [Not Specified]
4.Post-Hoc Outcome
Title LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect)
Hide Description LPS is defined as the duration of time measured in minutes from lights off to persistent sleep onset. In order to evaluate the efficacy of suvorexant on LPS excluding the influence of a carryover effect from Period 1 to Period 2, an ad hoc analysis of LPS restricted to Period 1 data was also performed.
Time Frame Night 1 (Period 1 only) and end of Week 4 (Period 1 only)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
Arm/Group Title Placebo Suvorexant 10 mg Suvorexant 20 mg Suvorexant 40 mg Suvorexant 80 mg
Hide Arm/Group Description:
Participants received dose-matched placebo to suvorexant daily prior to bedtime over 4 weeks in Treatment Period 1.
Participants received 10 mg suvorexant daily prior to bedtime over 4 weeks in Treatment Period 1.
Participants received 20 mg suvorexant daily prior to bedtime over 4 weeks in Treatment Period 1.
Participants received 40 mg suvorexant daily prior to bedtime over 4 weeks in Treatment Period 1.
Participants received 80 mg suvorexant daily prior to bedtime over 4 weeks in Treatment Period 1.
Overall Number of Participants Analyzed 127 31 33 32 31
Least Squares Mean (Standard Error)
Unit of Measure: minutes
Night 1 (n=127, 31, 33, 32, 31) 57.0  (4.29) 38.0  (7.67) 39.6  (7.41) 26.0  (7.56) 34.7  (7.67)
Week 4 (n=116, 29, 31, 30, 28) 52.4  (4.43) 32.2  (7.97) 27.7  (7.71) 36.6  (7.88) 32.8  (8.07)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 80 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -22.3
Confidence Interval (2-Sided) 95%
-38.3 to -6.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 80 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -19.6
Confidence Interval (2-Sided) 95%
-36.6 to -2.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 40 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -31.0
Confidence Interval (2-Sided) 95%
-46.9 to -15.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 40 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -15.7
Confidence Interval (2-Sided) 95%
-32.3 to 0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 20 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -17.4
Confidence Interval (2-Sided) 95%
-33.1 to -1.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 20 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -24.6
Confidence Interval (2-Sided) 95%
-41.0 to -8.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 10 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Night 1
Estimated Value -19.1
Confidence Interval (2-Sided) 95%
-35.1 to -3.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Suvorexant 10 mg
Comments A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference: Week 4
Estimated Value -20.2
Confidence Interval (2-Sided) 95%
-37.0 to -3.4
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Suvorexant 10 mg Suvorexant 20 mg Suvorexant 40 mg Suvorexant 80 mg
Hide Arm/Group Description Participants received dose-matched placebo to suvorexant daily prior to bedtime over a 4-week treatment period. Participants received 10 mg suvorexant daily prior to bedtime over a 4-week treatment period. Participants received 20 mg suvorexant daily prior to bedtime over a 4-week treatment period. Participants received 40 mg suvorexant daily prior to bedtime over a 4-week treatment period. Participants received 80 mg suvorexant daily prior to bedtime over a 4-week treatment period.
All-Cause Mortality
Placebo Suvorexant 10 mg Suvorexant 20 mg Suvorexant 40 mg Suvorexant 80 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Placebo Suvorexant 10 mg Suvorexant 20 mg Suvorexant 40 mg Suvorexant 80 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/249 (0.00%)      0/62 (0.00%)      0/61 (0.00%)      0/59 (0.00%)      0/61 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Suvorexant 10 mg Suvorexant 20 mg Suvorexant 40 mg Suvorexant 80 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/249 (3.61%)      1/62 (1.61%)      4/61 (6.56%)      11/59 (18.64%)      11/61 (18.03%)    
Infections and infestations           
Urinary tract infection  2/249 (0.80%)  2 0/62 (0.00%)  0 0/61 (0.00%)  0 3/59 (5.08%)  3 2/61 (3.28%)  2
Nervous system disorders           
Headache  6/249 (2.41%)  6 0/62 (0.00%)  0 1/61 (1.64%)  1 3/59 (5.08%)  3 3/61 (4.92%)  3
Somnolence  1/249 (0.40%)  1 1/62 (1.61%)  1 3/61 (4.92%)  3 7/59 (11.86%)  7 7/61 (11.48%)  8
1
Term from vocabulary, MedDRA 12.1
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.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck, Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00792298    
Other Study ID Numbers: 4305-006
2008_583 ( Other Identifier: Merck Registration Number )
First Submitted: November 10, 2008
First Posted: November 17, 2008
Results First Submitted: August 19, 2014
Results First Posted: November 14, 2014
Last Update Posted: November 6, 2018