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Safety and Efficacy Study of Suvorexant in Participants With Primary Insomnia - Study B (MK-4305-029)

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ClinicalTrials.gov Identifier: NCT01097629
Recruitment Status : Completed
First Posted : April 1, 2010
Results First Posted : September 1, 2014
Last Update Posted : July 2, 2017
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 Primary Insomnia
Interventions Drug: Suvorexant High Dose (HD)
Drug: Suvorexant Low Dose (LD)
Drug: Comparator: Placebo
Enrollment 1020
Recruitment Details  
Pre-assignment Details A 2-week single-blind placebo Run-in occurred prior to randomization. 1 of the 1020 randomized participants enrolled in 2 separate suvorexant trials and is excluded from all summaries and analyses. 10 other randomized participants were not treated and are in Participant Flow Table below, but are excluded from all other summaries and analyses.
Arm/Group Title Suvorexant Low Dose (LD) (TRT Phase) Suvorexant High Dose (HD) (TRT Phase) Placebo (TRT Phase) Suvorexant LD (Run-out [RO], After Suvorexant LD in TRT) Placebo (RO, After Suvorexant LD in TRT) Suvorexant HD (RO, After Suvorexant HD in TRT) Placebo (RO, After Suvorexant HD in TRT) Placebo (RO, After Placebo in TRT)
Hide Arm/Group Description After a 2-week single-blind placebo Run-in, participants received suvorexant LD (20 mg for participants aged 18 to <65 years; and 15 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase. After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase. After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase. After receiving suvorexant LD during the 3-Month DB TRT Phase, participants received their same dose of suvorexant during a 1-week DB RO Phase. After receiving suvorexant LD during the 3-Month DB TRT Phase, participants received placebo to suvorexant during a 1-week DB RO Phase. After receiving suvorexant HD during the 3-Month DB TRT Phase, participants received their same dose of suvorexant during a 1-week DB RO Phase. After receiving suvorexant HD during the 3-Month DB TRT Phase, participants received placebo to suvorexant during a 1-week DB RO Phase. After receiving placebo to suvorexant during the 3-Month DB TRT Phase, participants received placebo to suvorexant during a 1-week DB RO Phase.
Period Title: Double-Blind (DB) Treatment (TRT) Phase
Started 240 392 387 0 0 0 0 0
Treated 239 387 383 0 0 0 0 0
Completed 205 346 [1] 330 [2] 0 0 0 0 0
Not Completed 35 46 57 0 0 0 0 0
Reason Not Completed
Adverse Event             10             19             17             0             0             0             0             0
Withdrawal by Subject             8             9             19             0             0             0             0             0
Protocol Violation             5             4             8             0             0             0             0             0
Lost to Follow-up             2             4             1             0             0             0             0             0
Lack of Efficacy             7             4             8             0             0             0             0             0
Physician Decision             2             1             0             0             0             0             0             0
Not Treated             1             5             4             0             0             0             0             0
[1]
2 did not continue into RO
[2]
3 did not continue into RO
Period Title: DB RO Phase
Started 0 0 0 97 108 173 171 327
Completed 0 0 0 96 108 172 168 326
Not Completed 0 0 0 1 0 1 3 1
Reason Not Completed
Withdrawal by Subject             0             0             0             0             0             0             0             1
Protocol Violation             0             0             0             1             0             1             1             0
Lost to Follow-up             0             0             0             0             0             0             2             0
Arm/Group Title Suvorexant LD Suvorexant HD Placebo Total
Hide Arm/Group Description After a 2-week single-blind placebo Run-in, participants received suvorexant LD (20 mg for participants aged 18 to <65 years; and 15 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase. After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase. After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase. Total of all reporting groups
Overall Number of Baseline Participants 239 387 383 1009
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 239 participants 387 participants 383 participants 1009 participants
56  (16) 57  (15) 57  (15) 56  (15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 239 participants 387 participants 383 participants 1009 participants
Female
157
  65.7%
267
  69.0%
247
  64.5%
671
  66.5%
Male
82
  34.3%
120
  31.0%
136
  35.5%
338
  33.5%
Mean Subjective Total Sleep Time (sTSTm)   [1] 
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 239 participants 387 participants 383 participants 1009 participants
298.3  (81.9) 315.3  (77.0) 309.7  (77.1) 309.2  (78.4)
[1]
Measure Description: N=238, 386, 383, 1007 for Suvorexant Low Dose, Suvorexant High Dose, Placebo and Total, respectively.
Wakefulness After Persistent Sleep Onset (WASO)   [1] 
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 239 participants 387 participants 383 participants 1009 participants
119.6  (50.8) 119.4  (51.3) 118.4  (49.1) 119.0  (50.3)
[1]
Measure Description: N=150, 299, 295, 744 for Suvorexant Low Dose, Suvorexant High Dose, Placebo and Total, respectively. WASO was assessed during sleep laboratory (polysomnography [PSG]) assessment, which was conducted in a subset of the study population.
Mean Subjective Time to Sleep Onset (sTSOm)   [1] 
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 239 participants 387 participants 383 participants 1009 participants
86.0  (77.6) 74.4  (61.9) 81.3  (76.2) 79.8  (71.5)
[1]
Measure Description: N=238, 386, 383, 1007 for Suvorexant Low Dose, Suvorexant High Dose, Placebo and Total, respectively.
Latency to Onset of Persistent Sleep (LPS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 239 participants 387 participants 383 participants 1009 participants
65.3  (47.8) 67.3  (48.8) 68.0  (42.8) 67.2  (46.2)
[1]
Measure Description: N=150, 299, 295, 744 for Suvorexant Low Dose, Suvorexant High Dose, Placebo and Total, respectively. LPS was assessed during sleep laboratory (PSG) assessment, which was conducted in a subset of the study population.
1.Primary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) at Month 1
Hide Description sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily electronic diary (e-diary). Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any polysomnography [PSG] nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time Frame Baseline and Month 1
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 365 350
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
48.7
(43.1 to 54.3)
22.4
(16.7 to 28.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Month 1 sTSTm, had planned marginal power of 97.6%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments By multiplicity strategy above, overall Type I error among primary hypotheses was controlled at two-sided 5% significance level.
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, time by treatment interaction, and cohort (e-diary only, PSG-plus-e-diary).
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 26.3
Confidence Interval (2-Sided) 95%
18.3 to 34.3
Estimation Comments [Not Specified]
2.Primary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Month 3
Hide Description sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time Frame Baseline and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 340 325
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
62.8
(56.4 to 69.2)
37.7
(31.2 to 44.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Month 3 sTSTm, had planned marginal power of 95.7%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments By multiplicity strategy above, overall Type I error among primary hypotheses was controlled at two-sided 5% significance level.
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, time by treatment interaction, and cohort (e-diary only, PSG-plus-e-diary).
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 25.1
Confidence Interval 95%
16.0 to 34.2
Estimation Comments [Not Specified]
3.Primary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in Wakefulness After Persistent Sleep Onset (WASO) at Month 1
Hide Description WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time Frame Baseline and Month 1
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 278 270
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-51.9
(-56.9 to -46.9)
-22.5
(-27.5 to -17.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Month 1 WASO, had planned marginal power of 99.2%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments By multiplicity strategy above, overall Type I error among primary hypotheses was controlled at two-sided 5% significance level.
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, and time by treatment interaction.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -29.4
Confidence Interval (2-Sided) 95%
-36.6 to -22.3
Estimation Comments [Not Specified]
4.Primary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in WASO at Month 3
Hide Description WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time Frame Baseline and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 260 252
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-54.2
(-59.3 to -49.1)
-24.8
(-30.0 to -19.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Month 3 WASO, had planned marginal power of 98.3%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments By multiplicity strategy above, overall Type I error among primary hypotheses was controlled at two-sided 5% significance level.
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, and time by treatment interaction.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -29.4
Confidence Interval (2-Sided) 95%
-36.7 to -22.1
Estimation Comments [Not Specified]
5.Primary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Time to Sleep Onset (sTSOm) at Month 1
Hide Description sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time Frame Baseline and Month 1
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 365 350
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-26.9
(-31.1 to -22.8)
-14.1
(-18.4 to -9.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Month 1 sTSOm, had planned marginal power of 99.9%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00003
Comments By multiplicity strategy above, overall Type I error among primary hypotheses was controlled at two-sided 5% significance level.
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, time by treatment interaction, and cohort (e-diary only, PSG-plus-e-diary).
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -12.8
Confidence Interval (2-Sided) 95%
-18.8 to -6.9
Estimation Comments [Not Specified]
6.Primary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Month 3
Hide Description sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time Frame Baseline and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 340 325
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-33.7
(-38.0 to -29.3)
-20.5
(-24.9 to -16.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Month 3 sTSOm, had planned marginal power of 99.6%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00003
Comments By multiplicity strategy above, overall Type I error among primary hypotheses was controlled at two-sided 5% significance level.
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, time by treatment interaction, and cohort (e-diary only, PSG-plus-e-diary).
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -13.2
Confidence Interval (2-Sided) 95%
-19.4 to -7.0
Estimation Comments [Not Specified]
7.Primary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in Latency to Onset of Persistent Sleep (LPS) at Month 1
Hide Description LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment ("Lights-Off") to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time Frame Baseline and Month 1
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 280 271
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-36.7
(-40.8 to -32.7)
-24.6
(-28.7 to -20.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Month 1 LPS, had planned marginal power of 81.4%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00004
Comments By multiplicity strategy above, overall Type I error among primary hypotheses was controlled at two-sided 5% significance level.
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, and time by treatment interaction.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -12.1
Confidence Interval (2-Sided) 95%
-17.8 to -6.4
Estimation Comments [Not Specified]
8.Primary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in LPS at Month 3
Hide Description LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment ("Lights-Off") to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time Frame Baseline and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 262 255
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-32.2
(-36.7 to -27.7)
-28.6
(-33.1 to -24.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Month 3 LPS, had planned marginal power of 76.2%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints; the same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26510
Comments By multiplicity strategy above, overall Type I error among primary hypotheses was controlled at two-sided 5% significance level.
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, and time by treatment interaction.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -3.6
Confidence Interval (2-Sided) 95%
-10.1 to 2.8
Estimation Comments [Not Specified]
9.Primary Outcome
Title Number of Participants With an Adverse Event (AE) During 3-Month DB TRT Phase
Hide Description An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Participants with an AE occurring during the 3-month DB TRT Phase are counted once in this summary.
Time Frame Up to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Patients as Treated (APaT) population, consisting of all randomized participants who received at least one dose of study medication
Arm/Group Title Suvorexant LD Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant LD (20 mg for participants aged 18 to <65 years; and 15 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 239 387 383
Measure Type: Number
Unit of Measure: participants
103 189 167
10.Primary Outcome
Title Number of Participants Who Discontinued Study Drug Due to an AE Occurring During 3-Month DB TRT Phase
Hide Description An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Participants who discontinued study drug treatment due to an AE occurring during the 3-month DB TRT Phase are counted once in this summary.
Time Frame Up to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Patients as Treated (APaT) population, consisting of all randomized participants who received at least one dose of study medication
Arm/Group Title Suvorexant LD Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant LD (20 mg for participants aged 18 to <65 years; and 15 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 239 387 383
Measure Type: Number
Unit of Measure: participants
9 18 17
11.Secondary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Week 1
Hide Description sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Week 1 range is Days 2-8 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time Frame Baseline and Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 373 364
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
40.4
(35.7 to 45.1)
14.0
(9.2 to 18.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Week 1 sTSTm, had planned marginal power of 98.3%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints and either subjective or objective Month 3 endpoint must be significant to test Week 1/Night 1 endpoints. The same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, time by treatment interaction, and cohort (e-diary only, PSG-plus-e-diary).
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 26.4
Confidence Interval (2-Sided) 95%
19.8 to 33.1
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in WASO at Night 1
Hide Description WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time Frame Baseline and Night 1
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 285 283
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-63.3
(-68.0 to -58.6)
-21.3
(-26.1 to -16.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Night 1 WASO, had planned marginal power of 100.0%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints and either subjective or objective Month 3 endpoint must be significant to test Week 1/Night 1 endpoints. The same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, and time by treatment interaction.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -42.0
Confidence Interval (2-Sided) 95%
-48.6 to -35.3
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Week 1
Hide Description sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Week 1 range is Days 2-8 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.
Time Frame Baseline and Week 1
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization e-diary observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 373 364
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-19.7
(-23.0 to -16.4)
-6.7
(-10.0 to -3.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Week 1 sTSOm, had planned marginal power of 99.6%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints and either subjective or objective Month 3 endpoint must be significant to test Week 1/Night 1 endpoints. The same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, time by treatment interaction, and cohort (e-diary only, PSG-plus-e-diary).
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -13.1
Confidence Interval (2-Sided) 95%
-17.7 to -8.4
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Suvorexant HD Versus Placebo: Change From Baseline in LPS at Night 1
Hide Description LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment ("Lights-Off") to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.
Time Frame Baseline and Night 1
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with ≥1 post-randomization PSG observation after ≥1 dose of study drug, and baseline data were included in this analysis. The hypothesis included only the suvorexant HD-placebo comparison.
Arm/Group Title Suvorexant HD Placebo
Hide Arm/Group Description:
After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase.
After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase.
Overall Number of Participants Analyzed 289 284
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-34.7
(-39.5 to -29.9)
-13.0
(-17.8 to -8.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant HD, Placebo
Comments The null hypothesis, that suvorexant HD did not differ from placebo for Night 1 LPS, had planned marginal power of 100.0%. Sleep maintenance (sTSTm, WASO) and sleep onset (sTSOm, LPS) endpoints were tested at two-sided 2.5% significance level. Both Month 1 endpoints for sleep maintenance must be significant to test Month 3 endpoints and either subjective or objective Month 3 endpoint must be significant to test Week 1/Night 1 endpoints. The same approach was used for sleep onset endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Longitudinal Data Analysis
Comments Model terms: baseline value, age group, region, gender, treatment, time, and time by treatment interaction.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -21.7
Confidence Interval (2-Sided) 95%
-28.6 to -14.9
Estimation Comments [Not Specified]
Time Frame Up to 14 days after the last dose of study drug
Adverse Event Reporting Description The 3 TRT Phase reporting groups include total population; other groups present same or subsets of this population in other study phases. Events are reported by phase. Phases are: - TRT - RO - Follow-up (enter directly from TRT Phase, or from RO)
 
Arm/Group Title Suvorexant LD (TRT Phase) Suvorexant HD (TRT Phase) Placebo (TRT Phase) Suvorexant LD (RO, After Suvorexant LD in TRT) Placebo (RO, After Suvorexant LD in TRT) Suvorexant HD (RO, After Suvorexant HD in TRT) Placebo (RO, After Suvorexant HD in TRT) Placebo (RO, After Placebo in TRT) Suvorexant LD (TRT Phase): Follow-up Suvorexant HD (TRT Phase): Follow-up Placebo (TRT Phase): Follow-up Suvorexant LD (RO, After Suvorexant LD in TRT): Follow-up Placebo (RO, After Suvorexant LD in TRT): Follow-up Suvorexant HD (RO, After Suvorexant HD in TRT): Follow-up Placebo (RO, After Suvorexant HD in TRT): Follow-up Placebo (RO, After Placebo in TRT): Follow-up
Hide Arm/Group Description After a 2-week single-blind placebo Run-in, participants received suvorexant LD (20 mg for participants aged 18 to <65 years; and 15 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase. After a 2-week single-blind placebo Run-in, participants received suvorexant HD (40 mg for participants aged 18 to <65 years; and 30 mg for participants aged ≥65 years) daily before bedtime during the 3-month DB TRT Phase. After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month double-blind DB TRT Phase. After receiving suvorexant LD during the 3-Month DB TRT Phase, participants received their same dose of suvorexant during a 1-week DB RO Phase. After receiving suvorexant LD during the 3-Month DB TRT Phase, participants received placebo to suvorexant during a 1-week DB RO Phase. After receiving suvorexant HD during the 3-Month DB TRT Phase, participants received their same dose of suvorexant during a 1-week DB RO Phase. After receiving suvorexant HD during the 3-Month DB TRT Phase, participants received placebo to suvorexant during a 1-week DB RO Phase. After receiving placebo to suvorexant during the 3-Month DB TRT Phase, participants received placebo to suvorexant during a 1-week DB RO Phase. During 14-day Follow-up after last dose no study drug was administered. Follow-up AE data is presented for TRT Phase participants who entered Follow-up directly from TRT Phase and had received suvorexant LD during TRT Phase. During 14-day Follow-up after last dose no study drug was administered. Follow-up AE data is presented for TRT Phase participants who entered Follow-up directly from TRT Phase and had received suvorexant HD during TRT Phase. During 14-day Follow-up after last dose no study drug was administered. Follow-up AE data is presented for TRT Phase participants who entered Follow-up directly from TRT Phase and had received placebo during TRT Phase. During 14-day Follow-up after last dose no study drug was administered. Follow-up AE data is presented for RO participants who entered Follow-up from RO Phase, and had received suvorexant LD during TRT and RO Phases. During 14-day Follow-up after last dose no study drug was administered. Follow-up AE data is presented for RO participants who entered Follow-up from RO Phase, and had received suvorexant LD during TRT Phase and placebo during RO Phase. During 14-day Follow-up after last dose no study drug was administered. Follow-up AE data is presented for RO participants who entered Follow-up from RO Phase, and had received suvorexant HD during TRT and RO Phases. During 14-day Follow-up after last dose no study drug was administered. Follow-up AE data is presented for RO participants who entered Follow-up from RO Phase, and had received suvorexant HD during TRT Phase and placebo during RO Phase. During 14-day Follow-up after last dose no study drug was administered. Follow-up AE data is presented for RO participants who entered Follow-up from RO Phase, and had received placebo during TRT and RO Phases.
All-Cause Mortality
Suvorexant LD (TRT Phase) Suvorexant HD (TRT Phase) Placebo (TRT Phase) Suvorexant LD (RO, After Suvorexant LD in TRT) Placebo (RO, After Suvorexant LD in TRT) Suvorexant HD (RO, After Suvorexant HD in TRT) Placebo (RO, After Suvorexant HD in TRT) Placebo (RO, After Placebo in TRT) Suvorexant LD (TRT Phase): Follow-up Suvorexant HD (TRT Phase): Follow-up Placebo (TRT Phase): Follow-up Suvorexant LD (RO, After Suvorexant LD in TRT): Follow-up Placebo (RO, After Suvorexant LD in TRT): Follow-up Suvorexant HD (RO, After Suvorexant HD in TRT): Follow-up Placebo (RO, After Suvorexant HD in TRT): Follow-up Placebo (RO, After Placebo in TRT): 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 (%) 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
Suvorexant LD (TRT Phase) Suvorexant HD (TRT Phase) Placebo (TRT Phase) Suvorexant LD (RO, After Suvorexant LD in TRT) Placebo (RO, After Suvorexant LD in TRT) Suvorexant HD (RO, After Suvorexant HD in TRT) Placebo (RO, After Suvorexant HD in TRT) Placebo (RO, After Placebo in TRT) Suvorexant LD (TRT Phase): Follow-up Suvorexant HD (TRT Phase): Follow-up Placebo (TRT Phase): Follow-up Suvorexant LD (RO, After Suvorexant LD in TRT): Follow-up Placebo (RO, After Suvorexant LD in TRT): Follow-up Suvorexant HD (RO, After Suvorexant HD in TRT): Follow-up Placebo (RO, After Suvorexant HD in TRT): Follow-up Placebo (RO, After Placebo in TRT): 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 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   2/239 (0.84%)      6/387 (1.55%)      5/383 (1.31%)      0/97 (0.00%)      1/108 (0.93%)      0/173 (0.00%)      0/171 (0.00%)      0/327 (0.00%)      0/239 (0.00%)      1/387 (0.26%)      0/383 (0.00%)      0/97 (0.00%)      0/108 (0.00%)      0/173 (0.00%)      0/171 (0.00%)      0/327 (0.00%)    
Cardiac disorders                                 
atrial fibrillation  1/239 (0.42%)  1 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
Ear and labyrinth disorders                                 
Meniere's disease  0/239 (0.00%)  0 1/387 (0.26%)  1 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
Endocrine disorders                                 
autoimmune thyroiditis  0/239 (0.00%)  0 1/387 (0.26%)  1 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
Infections and infestations                                 
endometritis  0/239 (0.00%)  0 0/387 (0.00%)  0 1/383 (0.26%)  1 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
gastroenteritis  0/239 (0.00%)  0 0/387 (0.00%)  0 1/383 (0.26%)  1 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
meningitis  0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 1/108 (0.93%)  1 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
Injury, poisoning and procedural complications                                 
ankle fracture  1/239 (0.42%)  1 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
compression fracture  0/239 (0.00%)  0 1/387 (0.26%)  1 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
fall  0/239 (0.00%)  0 1/387 (0.26%)  1 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
ulna fracture  0/239 (0.00%)  0 1/387 (0.26%)  1 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
Musculoskeletal and connective tissue disorders                                 
musculoskeletal chest pain  0/239 (0.00%)  0 1/387 (0.26%)  1 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                 
bladder neoplasm  0/239 (0.00%)  0 0/387 (0.00%)  0 1/383 (0.26%)  1 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
malignant melanoma  0/239 (0.00%)  0 0/387 (0.00%)  0 1/383 (0.26%)  1 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
uterine leiomyoma  0/239 (0.00%)  0 0/387 (0.00%)  0 1/383 (0.26%)  1 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
Nervous system disorders                                 
cerebrovascular accident  0/239 (0.00%)  0 0/387 (0.00%)  0 1/383 (0.26%)  1 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
hypoxic-ischaemic encephalopathy  0/239 (0.00%)  0 1/387 (0.26%)  1 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
Psychiatric disorders                                 
alcohol withdrawal syndrome  0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 1/387 (0.26%)  1 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Suvorexant LD (TRT Phase) Suvorexant HD (TRT Phase) Placebo (TRT Phase) Suvorexant LD (RO, After Suvorexant LD in TRT) Placebo (RO, After Suvorexant LD in TRT) Suvorexant HD (RO, After Suvorexant HD in TRT) Placebo (RO, After Suvorexant HD in TRT) Placebo (RO, After Placebo in TRT) Suvorexant LD (TRT Phase): Follow-up Suvorexant HD (TRT Phase): Follow-up Placebo (TRT Phase): Follow-up Suvorexant LD (RO, After Suvorexant LD in TRT): Follow-up Placebo (RO, After Suvorexant LD in TRT): Follow-up Suvorexant HD (RO, After Suvorexant HD in TRT): Follow-up Placebo (RO, After Suvorexant HD in TRT): Follow-up Placebo (RO, After Placebo in TRT): 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 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   33/239 (13.81%)      59/387 (15.25%)      33/383 (8.62%)      0/97 (0.00%)      1/108 (0.93%)      4/173 (2.31%)      1/171 (0.58%)      4/327 (1.22%)      0/239 (0.00%)      2/387 (0.52%)      0/383 (0.00%)      0/97 (0.00%)      1/108 (0.93%)      0/173 (0.00%)      0/171 (0.00%)      1/327 (0.31%)    
Nervous system disorders                                 
headache  19/239 (7.95%)  22 29/387 (7.49%)  32 22/383 (5.74%)  22 0/97 (0.00%)  0 1/108 (0.93%)  1 3/173 (1.73%)  3 1/171 (0.58%)  1 4/327 (1.22%)  4 0/239 (0.00%)  0 2/387 (0.52%)  2 0/383 (0.00%)  0 0/97 (0.00%)  0 1/108 (0.93%)  1 0/173 (0.00%)  0 0/171 (0.00%)  0 1/327 (0.31%)  1
somnolence  20/239 (8.37%)  21 40/387 (10.34%)  44 12/383 (3.13%)  13 0/97 (0.00%)  0 0/108 (0.00%)  0 1/173 (0.58%)  1 0/171 (0.00%)  0 0/327 (0.00%)  0 0/239 (0.00%)  0 0/387 (0.00%)  0 0/383 (0.00%)  0 0/97 (0.00%)  0 0/108 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/327 (0.00%)  0
1
Term from vocabulary, MedDRA 14.1
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.
Investigator may publish results for his/her study site after publication of results of entire multicenter trial, or after public disclosure of the results online if a multicenter manuscript is not planned. Sponsor must be able to review all proposed results communications regarding study 60 days prior to submission for publication/presentation. Information identified by the Sponsor as confidential must be deleted prior to submission.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01097629     History of Changes
Other Study ID Numbers: 4305-029
2010_521 ( Other Identifier: Merck Registration Number )
CTRI/2010/091/001177 ( Registry Identifier: CTRI )
First Submitted: March 26, 2010
First Posted: April 1, 2010
Results First Submitted: August 19, 2014
Results First Posted: September 1, 2014
Last Update Posted: July 2, 2017