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Safety and Efficacy Study of Suvorexant in Participants With Primary Insomnia - Study A (MK-4305-028)

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ClinicalTrials.gov Identifier: NCT01097616
Recruitment Status : Completed
First Posted : April 1, 2010
Results First Posted : September 1, 2014
Last Update Posted : September 21, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Primary Insomnia
Interventions Drug: Suvorexant High Dose (HD)
Drug: Suvorexant Low Dose (LD)
Drug: Comparator: Placebo
Enrollment 1023
Recruitment Details  
Pre-assignment Details A 2-week single-blind placebo Run-in occurred prior to randomization. 1 of the 1023 randomized participants enrolled in 2 separate suvorexant trials and is excluded from all summaries and analyses. 1 other randomized participant was not treated and is in Participant Flow Table below, but is excluded from all other summaries and analyses.
Arm/Group Title Suvorexant Low Dose (LD) (TRT/Extension [EXT] Phase) Suvorexant High Dose (HD) (TRT/EXT Phase) Placebo (TRT/EXT Phase) Suvorexant LD (Run-out [RO], After Suvorexant LD in TRT/EXT) Placebo (RO, After Suvorexant LD in TRT/EXT) Suvorexant HD (RO, After Suvorexant HD in TRT/EXT) Placebo (RO, After Suvorexant HD in TRT/EXT) Placebo (RO, After Placebo in TRT/EXT)
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, and could continue on same dose during the optional 3-month DB EXT 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, and could continue on same dose during the optional 3-month DB EXT Phase. After a 2-week single-blind placebo Run-in, participants received placebo to suvorexant daily before bedtime during the 3-month DB TRT Phase, and could continue on placebo to suvorexant during the optional 3-month DB EXT Phase. After receiving suvorexant LD during the 3-Month DB TRT Phase, and for some participants, the optional 3-Month DB EXT 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, and for some participants, the optional 3-Month DB EXT Phase, participants received placebo to suvorexant during a 1-week DB RO Phase. After receiving suvorexant HD during the 3-Month DB TRT Phase, and for some participants, the optional 3-Month DB EXT 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, and for some participants, the optional 3-Month DB EXT 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, and for some participants, the optional 3-Month DB EXT Phase, participants received placebo to suvorexant during a 1-week DB RO Phase.
Period Title: Double-Blind (DB) Treatment (TRT) Phase
Started 254 383 385 0 0 0 0 0
Treated 254 383 384 0 0 0 0 0
Completed 230 [1] 345 [2] 341 [3] 0 0 0 0 0
Not Completed 24 38 44 0 0 0 0 0
Reason Not Completed
Adverse Event             6             15             21             0             0             0             0             0
Withdrawal by Subject             6             8             12             0             0             0             0             0
Protocol Violation             5             3             1             0             0             0             0             0
Lost to Follow-up             1             1             0             0             0             0             0             0
Lack of Efficacy             1             7             9             0             0             0             0             0
Pregnancy             1             1             0             0             0             0             0             0
Physician Decision             4             3             0             0             0             0             0             0
Not Treated             0             0             1             0             0             0             0             0
[1]
100 continued into EXT, 128 continued directly into RO, 2 did not continue into either Phase
[2]
172 continued into EXT, 172 continued directly into RO, 1 did not continue into either Phase
[3]
151 continued into EXT, 186 continued directly into RO, 4 did not continue into either Phase
Period Title: Optional DB EXT Phase
Started 100 172 151 0 0 0 0 0
Completed 85 [1] 151 [2] 141 [3] 0 0 0 0 0
Not Completed 15 21 10 0 0 0 0 0
Reason Not Completed
Adverse Event             0             7             2             0             0             0             0             0
Withdrawal by Subject             12             6             3             0             0             0             0             0
Protocol Violation             0             2             3             0             0             0             0             0
Lost to Follow-up             1             5             1             0             0             0             0             0
Lack of Efficacy             1             1             1             0             0             0             0             0
Physician Decision             1             0             0             0             0             0             0             0
[1]
All 85 continued into RO
[2]
All 151 continued into RO
[3]
All 141 continued into RO
Period Title: DB RO Phase
Started 0 0 0 101 112 [1] 161 [2] 162 327
Completed 0 0 0 100 111 159 161 326
Not Completed 0 0 0 1 1 2 1 1
Reason Not Completed
Adverse Event             0             0             0             0             0             0             1             0
Withdrawal by Subject             0             0             0             0             0             1             0             0
Lost to Follow-up             0             0             0             1             1             0             0             1
Not Treated in RO             0             0             0             0             0             1             0             0
[1]
1 was randomized to this group but actually received suvorexant LD during RO
[2]
1 entered RO but was not treated during RO
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 DB TRT Phase. Total of all reporting groups
Overall Number of Baseline Participants 254 383 384 1021
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 254 participants 383 participants 384 participants 1021 participants
55  (16) 56  (15) 56  (15) 56  (15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 254 participants 383 participants 384 participants 1021 participants
Female
162
  63.8%
230
  60.1%
245
  63.8%
637
  62.4%
Male
92
  36.2%
153
  39.9%
139
  36.2%
384
  37.6%
Mean Subjective Total Sleep Time (sTSTm)   [1] 
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 254 participants 383 participants 384 participants 1021 participants
322.4  (57.3) 316.1  (67.2) 315.7  (65.1) 317.5  (64.1)
[1]
Measure Description: N=252, 383, 384, 1019 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 254 participants 383 participants 384 participants 1021 participants
119.2  (46.5) 117.7  (49.6) 114.9  (45.7) 117.0  (47.4)
[1]
Measure Description: N=193, 291, 290, 774 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 254 participants 383 participants 384 participants 1021 participants
63.3  (37.1) 68.0  (50.1) 66.9  (40.5) 66.4  (43.6)
[1]
Measure Description: N=252, 383, 384, 1019 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 254 participants 383 participants 384 participants 1021 participants
68.9  (49.7) 61.8  (39.1) 66.2  (44.1) 65.2  (43.8)
[1]
Measure Description: N=193, 291, 290, 774 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 Primary 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 DB TRT Phase.
Overall Number of Participants Analyzed 363 365
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
42.6
(37.3 to 48.0)
23.1
(17.7 to 28.4)
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 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, and time by treatment interaction.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 19.6
Confidence Interval (2-Sided) 95%
12.0 to 27.1
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 Primary 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 DB TRT Phase.
Overall Number of Participants Analyzed 348 339
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
60.3
(54.8 to 65.8)
40.6
(35.0 to 46.1)
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 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, and time by treatment interaction.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 19.7
Confidence Interval (2-Sided) 95%
11.9 to 27.6
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 Primary 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 DB TRT Phase.
Overall Number of Participants Analyzed 272 272
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-45.0
(-50.1 to -39.9)
-18.7
(-23.7 to -13.6)
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 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 -26.3
Confidence Interval (2-Sided) 95%
-33.5 to -19.2
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 Primary 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 DB TRT Phase.
Overall Number of Participants Analyzed 251 251
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-47.9
(-53.2 to -42.6)
-25.0
(-30.3 to -19.8)
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 -22.9
Confidence Interval (2-Sided) 95%
-30.3 to -15.4
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 Primary 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 DB TRT Phase.
Overall Number of Participants Analyzed 363 365
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-19.1
(-22.6 to -15.7)
-11.7
(-15.2 to -8.2)
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 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 0.00298
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 -7.4
Confidence Interval (2-Sided) 95%
-12.3 to -2.5
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 Primary 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 DB TRT Phase.
Overall Number of Participants Analyzed 348 339
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-25.7
(-28.8 to -22.6)
-17.3
(-20.4 to -14.2)
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 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 0.00019
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 -8.4
Confidence Interval (2-Sided) 95%
-12.8 to -4.0
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 Primary 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 DB TRT Phase.
Overall Number of Participants Analyzed 275 272
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-34.5
(-38.1 to -30.9)
-23.3
(-26.9 to -19.7)
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 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 0.00002
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 -11.2
Confidence Interval (2-Sided) 95%
-16.3 to -6.1
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 Primary 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 DB TRT Phase.
Overall Number of Participants Analyzed 254 251
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-36.0
(-39.7 to -32.4)
-26.6
(-30.2 to -22.9)
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 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 0.00037
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 -9.4
Confidence Interval (2-Sided) 95%
-14.6 to -4.3
Estimation Comments [Not Specified]
9.Primary Outcome
Title Number of Participants With an Adverse Event (AE) During Initial 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 initial 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 DB TRT Phase.
Overall Number of Participants Analyzed 254 383 384
Measure Type: Number
Unit of Measure: participants
126 198 191
10.Primary Outcome
Title Number of Participants Who Discontinued Study Drug Due to an AE Occurring During Initial 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 initial 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 DB TRT Phase.
Overall Number of Participants Analyzed 254 383 384
Measure Type: Number
Unit of Measure: participants
6 18 23
11.Secondary Outcome
Title Suvorexant LD/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.
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 DB TRT Phase.
Overall Number of Participants Analyzed 248 379 376
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
28.2
(23.0 to 33.4)
36.0
(31.8 to 40.2)
14.6
(10.4 to 18.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments Sleep maintenance and sleep onset 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 the subjective or objective Month 3 endpoint must be significant to test the Week 1/Night 1 endpoints. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 0.00007
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 13.6
Confidence Interval (2-Sided) 95%
6.9 to 20.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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, and time by treatment interaction.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 21.4
Confidence Interval (2-Sided) 95%
15.5 to 27.4
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Suvorexant LD Versus Placebo: Change From Baseline in 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 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. Only suvorexant LD-placebo comparison included, as suvorexant HD-placebo comparison is included in Primary hypothesis.
Arm/Group Title Suvorexant LD 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 placebo to suvorexant daily before bedtime during the 3-month DB TRT Phase.
Overall Number of Participants Analyzed 244 365
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
39.4
(32.8 to 45.9)
23.1
(17.7 to 28.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments 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. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 0.00016
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 16.3
Confidence Interval (2-Sided) 95%
7.9 to 24.8
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Suvorexant LD 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. Only suvorexant LD-placebo comparison included, as suvorexant HD-placebo comparison is included in Primary hypothesis.
Arm/Group Title Suvorexant LD 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 placebo to suvorexant daily before bedtime during the 3-month DB TRT Phase.
Overall Number of Participants Analyzed 228 339
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
51.2
(44.4 to 58.1)
40.6
(35.0 to 46.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments 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. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 0.01711
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 10.7
Confidence Interval (2-Sided) 95%
1.9 to 19.5
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Suvorexant LD/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.
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 DB TRT Phase.
Overall Number of Participants Analyzed 192 291 287
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-52.1
(-57.4 to -46.8)
-58.0
(-62.3 to -53.7)
-19.6
(-23.9 to -15.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments Sleep maintenance and sleep onset 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 the subjective or objective Month 3 endpoint must be significant to test the Week 1/Night 1 endpoints. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 -32.5
Confidence Interval (2-Sided) 95%
-39.3 to -25.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 -38.4
Confidence Interval (2-Sided) 95%
-44.5 to -32.3
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Suvorexant LD Versus Placebo: Change From Baseline in 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. Only suvorexant LD-placebo comparison included, as suvorexant HD-placebo comparison is included in Primary hypothesis.
Arm/Group Title Suvorexant LD 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 placebo to suvorexant daily before bedtime during the 3-month DB TRT Phase.
Overall Number of Participants Analyzed 185 272
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-45.0
(-51.2 to -38.9)
-18.7
(-23.7 to -13.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments 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. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 -26.4
Confidence Interval (2-Sided) 95%
-34.3 to -18.4
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Suvorexant LD 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. Only suvorexant LD-placebo comparison included, as suvorexant HD-placebo comparison is included in Primary hypothesis.
Arm/Group Title Suvorexant LD 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 placebo to suvorexant daily before bedtime during the 3-month DB TRT Phase.
Overall Number of Participants Analyzed 172 251
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-41.6
(-48.0 to -35.2)
-25.0
(-30.3 to -19.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments 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. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 0.00009
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 -16.6
Confidence Interval (2-Sided) 95%
-24.8 to -8.3
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Suvorexant LD/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.
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 DB TRT Phase.
Overall Number of Participants Analyzed 248 379 376
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-15.2
(-18.7 to -11.7)
-15.3
(-18.1 to -12.4)
-9.6
(-12.5 to -6.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments Sleep maintenance and sleep onset 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 the subjective or objective Month 3 endpoint must be significant to test the Week 1/Night 1 endpoints. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 0.01564
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 -5.6
Confidence Interval (2-Sided) 95%
-10.2 to -1.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.00609
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 -5.7
Confidence Interval (2-Sided) 95%
-9.7 to -1.6
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Suvorexant LD Versus Placebo: Change From Baseline in 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. Only suvorexant LD-placebo comparison included, as suvorexant HD-placebo comparison is included in Primary hypothesis.
Arm/Group Title Suvorexant LD 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 placebo to suvorexant daily before bedtime during the 3-month DB TRT Phase.
Overall Number of Participants Analyzed 244 365
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-17.1
(-21.4 to -12.9)
-11.7
(-15.2 to -8.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments 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. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 0.05191
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 -5.4
Confidence Interval (2-Sided) 95%
-10.9 to 0.0
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Suvorexant LD 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. Only suvorexant LD-placebo comparison included, as suvorexant HD-placebo comparison is included in Primary hypothesis.
Arm/Group Title Suvorexant LD 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 placebo to suvorexant daily before bedtime during the 3-month DB TRT Phase.
Overall Number of Participants Analyzed 228 339
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-22.5
(-26.3 to -18.7)
-17.3
(-20.4 to -14.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments 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. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 0.03771
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 -5.2
Confidence Interval (2-Sided) 95%
-10.2 to -0.3
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Suvorexant LD/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.
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 DB TRT Phase.
Overall Number of Participants Analyzed 193 291 290
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-29.9
(-34.0 to -25.8)
-30.6
(-33.9 to -27.2)
-20.3
(-23.6 to -17.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments Sleep maintenance and sleep onset 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 the subjective or objective Month 3 endpoint must be significant to test the Week 1/Night 1 endpoints. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 0.00041
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 -9.6
Confidence Interval (2-Sided) 95%
-14.9 to -4.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.00002
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 -10.3
Confidence Interval (2-Sided) 95%
-15.0 to -5.5
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Suvorexant LD Versus Placebo: Change From Baseline in 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. Only suvorexant LD-placebo comparison included, as suvorexant HD-placebo comparison is included in Primary hypothesis.
Arm/Group Title Suvorexant LD 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 placebo to suvorexant daily before bedtime during the 3-month DB TRT Phase.
Overall Number of Participants Analyzed 185 272
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-33.6
(-37.9 to -29.2)
-23.3
(-26.9 to -19.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments 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. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 0.00040
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 -10.3
Confidence Interval (2-Sided) 95%
-16.0 to -4.6
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Suvorexant LD 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. Only suvorexant LD-placebo comparison included, as suvorexant HD-placebo comparison is included in Primary hypothesis.
Arm/Group Title Suvorexant LD 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 placebo to suvorexant daily before bedtime during the 3-month DB TRT Phase.
Overall Number of Participants Analyzed 172 251
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-34.7
(-39.1 to -30.2)
-26.6
(-30.2 to -22.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Suvorexant LD, Placebo
Comments 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. A sleep maintenance LD endpoint was tested if ≥1 HD Month 3 endpoint for sleep maintenance and corresponding HD endpoint were significant. 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 0.00606
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 -8.1
Confidence Interval (2-Sided) 95%
-13.8 to -2.3
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 - EXT - RO (enter from TRT or EXT phase) - Follow-up (enter directly from TRT or EXT Phase, or from RO). Participants are allocated to treatment actually received.
 
Arm/Group Title Suvorexant LD (TRT Phase) Suvorexant HD (TRT Phase) Placebo (TRT Phase) Suvorexant LD (EXT Phase) Suvorexant HD (EXT Phase) Placebo (EXT Phase) Suvorexant LD (RO, After Suvorexant LD in TRT/EXT) Placebo (RO, After Suvorexant LD in TRT/EXT) Suvorexant HD (RO, After Suvorexant HD in TRT/EXT) Placebo (RO, After Suvorexant HD in TRT/EXT) Placebo (RO, After Placebo in TRT/EXT) Suvorexant LD (TRT/EXT Phase): Follow-up Suvorexant HD (TRT/EXT Phase): Follow-up Placebo (TRT/EXT Phase): Follow-up Suvorexant LD (RO, After Suvorexant LD in TRT/EXT): Follow-up Placebo (RO, After Suvorexant LD in TRT/EXT): Follow-up Suvorexant HD (RO, After Suvorexant HD in TRT/EXT): Follow-up Placebo (RO, After Suvorexant HD in TRT/EXT): Follow-up Placebo (RO, After Placebo in TRT/EXT): 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 DB TRT Phase. After receiving suvorexant LD during the 3-month DB TRT Phase, participants could continue on same dose during the optional 3-month DB EXT Phase. After receiving suvorexant HD during the 3-month DB TRT Phase, participants could continue on same dose during the optional 3-month DB EXT Phase. After receiving placebo to suvorexant during the 3-month DB TRT Phase, participants could continue on placebo to suvorexant during the optional 3-month DB EXT Phase. After receiving suvorexant LD during the 3-Month DB TRT Phase, and for some participants, the optional 3-Month DB EXT 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, and for some participants, the optional 3-Month DB EXT Phase, participants received placebo to suvorexant during a 1-week DB RO Phase. After receiving suvorexant HD during the 3-Month DB TRT Phase, and for some participants, the optional 3-Month DB EXT 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, and for some participants, the optional 3-Month DB EXT 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, and for some participants, the optional 3-Month DB EXT 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/EXT participants who entered Follow-up directly from TRT or EXT Phase and had received suvorexant LD during TRT/EXT Phase. During 14-day Follow-up after last dose no study drug was administered. Follow-up AE data is presented for TRT/EXT participants who entered Follow-up directly from TRT or EXT Phase and had received suvorexant HD during TRT/EXT Phase. During 14-day Follow-up after last dose no study drug was administered. Follow-up AE data is presented for TRT/EXT participants who entered Follow-up directly from TRT or EXT Phase and had received placebo during TRT/EXT 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/EXT 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/EXT 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/EXT 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/EXT 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/EXT and RO Phases.
All-Cause Mortality
Suvorexant LD (TRT Phase) Suvorexant HD (TRT Phase) Placebo (TRT Phase) Suvorexant LD (EXT Phase) Suvorexant HD (EXT Phase) Placebo (EXT Phase) Suvorexant LD (RO, After Suvorexant LD in TRT/EXT) Placebo (RO, After Suvorexant LD in TRT/EXT) Suvorexant HD (RO, After Suvorexant HD in TRT/EXT) Placebo (RO, After Suvorexant HD in TRT/EXT) Placebo (RO, After Placebo in TRT/EXT) Suvorexant LD (TRT/EXT Phase): Follow-up Suvorexant HD (TRT/EXT Phase): Follow-up Placebo (TRT/EXT Phase): Follow-up Suvorexant LD (RO, After Suvorexant LD in TRT/EXT): Follow-up Placebo (RO, After Suvorexant LD in TRT/EXT): Follow-up Suvorexant HD (RO, After Suvorexant HD in TRT/EXT): Follow-up Placebo (RO, After Suvorexant HD in TRT/EXT): Follow-up Placebo (RO, After Placebo in TRT/EXT): 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 (%) 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 (EXT Phase) Suvorexant HD (EXT Phase) Placebo (EXT Phase) Suvorexant LD (RO, After Suvorexant LD in TRT/EXT) Placebo (RO, After Suvorexant LD in TRT/EXT) Suvorexant HD (RO, After Suvorexant HD in TRT/EXT) Placebo (RO, After Suvorexant HD in TRT/EXT) Placebo (RO, After Placebo in TRT/EXT) Suvorexant LD (TRT/EXT Phase): Follow-up Suvorexant HD (TRT/EXT Phase): Follow-up Placebo (TRT/EXT Phase): Follow-up Suvorexant LD (RO, After Suvorexant LD in TRT/EXT): Follow-up Placebo (RO, After Suvorexant LD in TRT/EXT): Follow-up Suvorexant HD (RO, After Suvorexant HD in TRT/EXT): Follow-up Placebo (RO, After Suvorexant HD in TRT/EXT): Follow-up Placebo (RO, After Placebo in TRT/EXT): 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/254 (0.39%)      0/383 (0.00%)      11/384 (2.86%)      0/100 (0.00%)      3/172 (1.74%)      0/151 (0.00%)      0/102 (0.00%)      0/111 (0.00%)      0/160 (0.00%)      1/162 (0.62%)      0/327 (0.00%)      0/254 (0.00%)      1/383 (0.26%)      0/384 (0.00%)      0/102 (0.00%)      0/111 (0.00%)      0/160 (0.00%)      0/162 (0.00%)      0/327 (0.00%)    
Cardiac disorders                                       
atrial fibrillation  0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 1/162 (0.62%)  1 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
myocardial infarction  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
Gastrointestinal disorders                                       
colitis  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
duodenal ulcer  0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/100 (0.00%)  0 1/172 (0.58%)  1 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
Infections and infestations                                       
gastroenteritis  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
pneumonia  1/254 (0.39%)  1 0/383 (0.00%)  0 0/384 (0.00%)  0 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
Injury, poisoning and procedural complications                                       
fall  0/254 (0.00%)  0 0/383 (0.00%)  0 2/384 (0.52%)  2 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
fibula fracture  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
rib fracture  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
tibia fracture  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
Musculoskeletal and connective tissue disorders                                       
intervertebral disc protrusion  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                       
basal cell carcinoma  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  5 0/100 (0.00%)  0 1/172 (0.58%)  2 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
borderline ovarian tumor  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
breast cancer  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
Nervous system disorders                                       
cerebrovascular accident  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
subarachnoid haemorrage  0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/100 (0.00%)  0 1/172 (0.58%)  1 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
Pregnancy, puerperium and perinatal conditions                                       
abortion spontaneous  0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 1/383 (0.26%)  1 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
Psychiatric disorders                                       
depressed mood  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
suicidal ideation  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                                       
pneumothorax  0/254 (0.00%)  0 0/383 (0.00%)  0 1/384 (0.26%)  1 0/100 (0.00%)  0 0/172 (0.00%)  0 0/151 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (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 (EXT Phase) Suvorexant HD (EXT Phase) Placebo (EXT Phase) Suvorexant LD (RO, After Suvorexant LD in TRT/EXT) Placebo (RO, After Suvorexant LD in TRT/EXT) Suvorexant HD (RO, After Suvorexant HD in TRT/EXT) Placebo (RO, After Suvorexant HD in TRT/EXT) Placebo (RO, After Placebo in TRT/EXT) Suvorexant LD (TRT/EXT Phase): Follow-up Suvorexant HD (TRT/EXT Phase): Follow-up Placebo (TRT/EXT Phase): Follow-up Suvorexant LD (RO, After Suvorexant LD in TRT/EXT): Follow-up Placebo (RO, After Suvorexant LD in TRT/EXT): Follow-up Suvorexant HD (RO, After Suvorexant HD in TRT/EXT): Follow-up Placebo (RO, After Suvorexant HD in TRT/EXT): Follow-up Placebo (RO, After Placebo in TRT/EXT): 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/254 (17.72%)      87/383 (22.72%)      67/384 (17.45%)      6/100 (6.00%)      14/172 (8.14%)      3/151 (1.99%)      1/102 (0.98%)      0/111 (0.00%)      0/160 (0.00%)      2/162 (1.23%)      3/327 (0.92%)      0/254 (0.00%)      1/383 (0.26%)      1/384 (0.26%)      0/102 (0.00%)      0/111 (0.00%)      1/160 (0.63%)      1/162 (0.62%)      2/327 (0.61%)    
Infections and infestations                                       
nasopharnygitis  18/254 (7.09%)  18 32/383 (8.36%)  33 34/384 (8.85%)  35 4/100 (4.00%)  4 9/172 (5.23%)  10 1/151 (0.66%)  1 1/102 (0.98%)  1 0/111 (0.00%)  0 0/160 (0.00%)  0 1/162 (0.62%)  1 1/327 (0.31%)  1 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 1/162 (0.62%)  1 2/327 (0.61%)  2
Nervous system disorders                                       
headache  17/254 (6.69%)  19 26/383 (6.79%)  33 23/384 (5.99%)  28 1/100 (1.00%)  1 2/172 (1.16%)  4 1/151 (0.66%)  1 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 1/162 (0.62%)  1 2/327 (0.61%)  2 0/254 (0.00%)  0 1/383 (0.26%)  3 1/384 (0.26%)  1 0/102 (0.00%)  0 0/111 (0.00%)  0 1/160 (0.63%)  1 0/162 (0.00%)  0 0/327 (0.00%)  0
somnolence  13/254 (5.12%)  14 41/383 (10.70%)  41 13/384 (3.39%)  13 1/100 (1.00%)  1 3/172 (1.74%)  3 1/151 (0.66%)  1 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (0.00%)  0 0/327 (0.00%)  0 0/254 (0.00%)  0 0/383 (0.00%)  0 0/384 (0.00%)  0 0/102 (0.00%)  0 0/111 (0.00%)  0 0/160 (0.00%)  0 0/162 (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: NCT01097616     History of Changes
Other Study ID Numbers: 4305-028
2010_520 ( Other Identifier: Merck Registration Number )
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: September 21, 2018