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

• 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: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• 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

Participant Flow

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)
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

Baseline Characteristics

Arm/Group Title		Suvorexant LD	Suvorexant HD	Placebo	Total
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
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.

Outcome Measures

1. Primary Outcome

Title	Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) at Month 1
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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)

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]

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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]

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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]

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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]

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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]

Adverse Events

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

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

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

--/--

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 1

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 1

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 1

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 1

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 1

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

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 1

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 1

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 1

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 1

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 1

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 1

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 1

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 1

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 1

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 1

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 1

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 1

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 1

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 1

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

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 1

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 1

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 1

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

Limitations and Caveats

[Not Specified]

More Information

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
• EMail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Herring WJ, Connor KM, Ivgy-May N, Snyder E, Liu K, Snavely DB, Krystal AD, Walsh JK, Benca RM, Rosenberg R, Sangal RB, Budd K, Hutzelmann J, Leibensperger H, Froman S, Lines C, Roth T, Michelson D. Suvorexant in Patients With Insomnia: Results From Two 3-Month Randomized Controlled Clinical Trials. Biol Psychiatry. 2016 Jan 15;79(2):136-48. doi: 10.1016/j.biopsych.2014.10.003. Epub 2014 Oct 23.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Snyder ES, Tao P, Svetnik V, Lines C, Herring WJ. Use of the single-item Patient Global Impression-Severity scale as a self-reported assessment of insomnia severity. J Sleep Res. 2021 Feb;30(1):e13141. doi: 10.1111/jsr.13141. Epub 2020 Jul 30.

Svetnik V, Snyder ES, Tao P, Roth T, Lines C, Herring WJ. How well can a large number of polysomnography sleep measures predict subjective sleep quality in insomnia patients? Sleep Med. 2020 Mar;67:137-146. doi: 10.1016/j.sleep.2019.08.020. Epub 2019 Sep 11.

Herring WJ, Connor KM, Snyder E, Snavely DB, Morin CM, Lines C, Michelson D. Effects of suvorexant on the Insomnia Severity Index in patients with insomnia: analysis of pooled phase 3 data. Sleep Med. 2019 Apr;56:219-223. doi: 10.1016/j.sleep.2018.09.010. Epub 2018 Oct 2.

Svetnik V, Snyder ES, Tao P, Scammell TE, Roth T, Lines C, Herring WJ. Insight Into Reduction of Wakefulness by Suvorexant in Patients With Insomnia: Analysis of Wake Bouts. Sleep. 2018 Jan 1;41(1). doi: 10.1093/sleep/zsx178.

Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. Suvorexant in Elderly Patients with Insomnia: Pooled Analyses of Data from Phase III Randomized Controlled Clinical Trials. Am J Geriatr Psychiatry. 2017 Jul;25(7):791-802. doi: 10.1016/j.jagp.2017.03.004. Epub 2017 Mar 8.

Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. Clinical profile of suvorexant for the treatment of insomnia over 3 months in women and men: subgroup analysis of pooled phase-3 data. Psychopharmacology (Berl). 2017 Jun;234(11):1703-1711. doi: 10.1007/s00213-017-4573-1. Epub 2017 Mar 7.

Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials. J Clin Sleep Med. 2016 Sep 15;12(9):1215-25. doi: 10.5664/jcsm.6116.

Snyder E, Ma J, Svetnik V, Connor KM, Lines C, Michelson D, Herring WJ. Effects of suvorexant on sleep architecture and power spectral profile in patients with insomnia: analysis of pooled phase 3 data. Sleep Med. 2016 Mar;19:93-100. doi: 10.1016/j.sleep.2015.10.007. Epub 2015 Nov 10.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01097616
• 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