A Study to Evaluate Safety and Efficacy of SAGE-547 in Pa... | NCT02942017

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received an infusion rate equivalent to the 90 micrograms per kilogram per hour (μg/kg/h) group.	Drug: Placebo
SAGE-547 90 μg/kg/h	Experimental	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).	Drug: SAGE-547 90 μg/kg/h

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Intravenous infusion of matching placebo for SAGE-547.	Placebo

Measure	Description	Time Frame
Change From Baseline at 60 Hours in 17-Item Hamilton Rating Scale for Depression (HAM-D) Total Score	The HAM-D Total Score comprises a sum of the 17 individual item scores. Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The Total Score can range from 0 to 52, and higher scores indicate a greater degree of depression. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.	Baseline, Hour 60

Measure	Description	Time Frame
Change From Baseline in HAM-D Total Score at Day 30	The HAM-D Total Score comprises a sum of the 17 individual item scores. Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The Total Score can range from 0 to 52, and higher scores indicate a greater degree of depression. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.

Name	Affiliation	Role
Helen Colquhoun, MD	Sage Therapeutics	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Sage Investigational Site		Chandler	Arizona	85226	United States
Sage Investigational Site

PubMed Identifier	Type	Citation	Retractions
33181049	Derived	Gerbasi ME, Meltzer-Brody S, Acaster S, Fridman M, Bonthapally V, Hodgkins P, Kanes SJ, Eldar-Lissai A. Brexanolone in Postpartum Depression: Post Hoc Analyses to Help Inform Clinical Decision-Making. J Womens Health (Larchmt). 2021 Mar;30(3):385-392. doi: 10.1089/jwh.2020.8483. Epub 2020 Nov 12.
30177236	Derived

Label	URL
Related Info	View source

ID	Title	Description
FG000	Placebo	Participants received an infusion rate equivalent to the 90 micrograms per kilogram per hour (μg/kg/h) group.
FG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 16, 2017	Apr 11, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline at 60 Hours in 17-Item Hamilton Rating Scale for Depression (HAM-D) Total Score

The HAM-D Total Score comprises a sum of the 17 individual item scores. Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The Total Score can range from 0 to 52, and higher scores indicate a greater degree of depression. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.

All randomized participants who started study drug infusion, had a valid baseline HAM-D assessment and at least one post-baseline HAM-D assessment. Overall number of participants analyzed is the number of participants with data available for analysis at the given time-point.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Hour 60

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Units	Counts
Participants	OG00052 OG00149

Title

Denominators

Categories

Title	Measurements
	OG000-12.12± 0.773 OG001-14.62± 0.782

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Mixed effect model for repeated measures (MMRM) was used for analysis. The change from baseline in HAM-D total score at each visit was the dependent variable. Treatment, baseline HAM-D total score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM		0.0160		Least Square (LS) Mean Difference	-2.50	Standard Error of the Mean	1.019	2-Sided	95	-4.52	-0.48					Superiority

Secondary

Change From Baseline in HAM-D Total Score at Day 30

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Day 30

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Secondary

Change From Baseline in HAM-D Total Score

All randomized participants who started study drug infusion, had a valid baseline HAM-D assessment and at least one post-baseline HAM-D assessment. Number analyzed is the number of participants with data available for analysis at the given time point.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Hours 2, 4, 8, 12, 24, 36, 48, 72, and Days 7, 14 and 21

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Secondary

Percentage of Participants With HAM-D Response

The HAM-D response is defined as having a 50% or greater reduction from baseline in HAM-D total score. The HAM-D Total Score comprises a sum of the 17 individual item scores. Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The Total Score can range from 0 to 52, and higher scores indicate a greater degree of depression. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.

Posted

Number

percentage of participants

Hour 60, Days 7 and 30

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Secondary

Percentage of Participants With HAM-D Remission

HAM-D remission is defined as having a HAM-D total score of ≤7. The HAM-D Total Score comprises a sum of the 17 individual item scores. Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The Total Score can range from 0 to 52, and higher scores indicate a greater degree of depression. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.

Posted

Number

percentage of participants

Hour 60, Days 7 and 30

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Secondary

Change From Baseline in HAM-D Bech 6 Subscale

The HAM-D Bech 6 subscale score is calculated as the sum of the following six items: Item # 1 (depressed mood), Item # 2 (feelings of guilt), Item # 7 (work and activities), Item # 8 (retardation), Item # 10 (anxiety psychic), and Item # 13 (general somatic symptoms). Each item is scored in a range of 0 to 2 or 0 to 4, with higher scores indicating a greater degree of depression. The scores were transformed to a 100-point scale with a higher score indicating a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Hour 60, Days 7 and 30

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Secondary

Change From Baseline in HAM-D Individual Item Scores

The HAM-D comprises individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Hours 2, 4, 8, 12, 24, 36, 48, 60, 72, and Days 7, 14, 21, and 30

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Secondary

Change From Baseline at Key Time Points in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

The MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in participants with mood disorders. It was designed as an adjunct to the HAM-D, to be more sensitive than the Hamilton Scale to the changes brought on by antidepressants and other forms of treatment. Each item yielded a score of 0 to 6. The MADRS total score was calculated as the sum of the 10 individual item scores, which ranged from 0 to 60. Higher MADRS scores indicates more severe depression. A negative change from baseline indicates less severe depression. A positive change from baseline indicates more severe depression.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Hour 60, Days 7 and 30

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Secondary

Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response

The CGI-I response was defined as having a score of 1 (very much improved) or 2 (much improved). CGI-I item employs a 7-point Likert scale to measure the overall improvement in the participant's condition post-treatment. The investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. Response choices include: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The CGI-I was only rated at post-treatment assessments. By definition, all CGI-I assessments were evaluated against baseline conditions.

Posted

Number

percentage of participants

Hour 60, Days 7 and 30

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Secondary

Change From Baseline in the Generalized Anxiety Disorder 7-Item Scale (GAD-7) Total Score

The GAD-7 is a participant-rated, generalized anxiety symptom severity scale. Scoring for GAD-7 generalized anxiety is calculated by assigning scores of 0 = "not at all sure," 1 = "several days," 2 = "over half the days," and 3 = "nearly every day" to the response categories. The GAD-7 total score for the seven items ranges from 0 to 21, where a score of 0 to 4 = minimal anxiety, 5 to 9 = mild anxiety, 10 to 14 = moderate anxiety, and 15 to 21 = severe anxiety. The GAD-7 total score was calculated as the sum of the seven individual item scores. A negative change from baseline indicates less anxiety. A positive change from baseline indicates more anxiety.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Hour 60, Days 7, 14, 21 and 30

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Secondary

Percentage of Participants With Treatment Emergent Adverse Event (TEAE)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE with onset on or after the start of study drug infusion, or any worsening of a pre-existing medical condition/AE with onset on or after the start of study drug infusion.

The safety set included all randomized participants who started the study drug infusion.

Posted

Number

percentage of participants

Up to approximately 37 days

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Secondary

Time to Change in Antidepressant Medication

The time to first start or increase in the dose and time to first stop or decrease in the dose of any antidepressant medication.

Posted

Median

Full Range

days

Up to approximately 37 days

ID	Title	Description
OG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
OG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).

Units	Counts
Participants	OG000

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Depressed Mood, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5132	LS Mean Difference	-0.10	Standard Error of the Mean	0.154	2-Sided	95	-0.41	0.21	Superiority
OG000 OG001	Depressed Mood, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1672	LS Mean Difference	-0.25	Standard Error of the Mean	0.181	2-Sided	95	-0.61	0.11	Superiority
OG000 OG001	Depressed Mood, Hour 8:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0963	LS Mean Difference	-0.30	Standard Error of the Mean	0.178	2-Sided	95	-0.65	0.05	Superiority
OG000 OG001	Depressed Mood, Hour 12:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4803	LS Mean Difference	-0.13	Standard Error of the Mean	0.183	2-Sided	95	-0.49	0.23	Superiority
OG000 OG001	Depressed Mood, Hour 24:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0844	LS Mean Difference	-0.33	Standard Error of the Mean	0.191	2-Sided	95	-0.71	0.05	Superiority
OG000 OG001	Depressed Mood, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1325	LS Mean Difference	-0.29	Standard Error of the Mean	0.193	2-Sided	95	-0.68	0.09	Superiority
OG000 OG001	Depressed Mood, Hour 48:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0332	LS Mean Difference	-0.41	Standard Error of the Mean	0.192	2-Sided	95	-0.79	-0.03	Superiority
OG000 OG001	Depressed Mood, Hour 60:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1273	LS Mean Difference	-0.29	Standard Error of the Mean	0.189	2-Sided	95	-0.67	0.08	Superiority
OG000 OG001	Depressed Mood, Hour 72:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1059	LS Mean Difference	-0.30	Standard Error of the Mean	0.182	2-Sided	95	-0.66	0.06	Superiority
OG000 OG001	Depressed Mood, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0683	LS Mean Difference	-0.40	Standard Error of the Mean	0.215	2-Sided	95	-0.82	0.03	Superiority
OG000 OG001	Depressed Mood, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4458	LS Mean Difference	-0.18	Standard Error of the Mean	0.232	2-Sided	95	-0.64	0.28	Superiority
OG000 OG001	Depressed Mood, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2905	LS Mean Difference	0.24	Standard Error of the Mean	0.228	2-Sided	95	-0.21	0.70	Superiority
OG000 OG001	Depressed Mood, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3096	LS Mean Difference	0.19	Standard Error of the Mean	0.182	2-Sided	95	-0.18	0.55	Superiority
OG000 OG001	Feeling of Guilt, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1925	LS Mean Difference	-0.22	Standard Error of the Mean	0.165	2-Sided	95	-0.55	0.11	Superiority
OG000 OG001	Feeling of Guilt, Hour 4:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0101	LS Mean Difference	-0.44	Standard Error of the Mean	0.168	2-Sided	95	-0.77	-0.11	Superiority
OG000 OG001	Feeling of Guilt, Hour 8:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1546	LS Mean Difference	-0.23	Standard Error of the Mean	0.163	2-Sided	95	-0.56	0.09	Superiority
OG000 OG001	Feeling of Guilt, Hour 12:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0901	LS Mean Difference	-0.29	Standard Error of the Mean	0.168	2-Sided	95	-0.62	0.05	Superiority
OG000 OG001	Feeling of Guilt, Hour 24:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0717	LS Mean Difference	-0.29	Standard Error of the Mean	0.162	2-Sided	95	-0.62	0.03	Superiority
OG000 OG001	Feeling of Guilt, Hour 36:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0468	LS Mean Difference	-0.34	Standard Error of the Mean	0.169	2-Sided	95	-0.68	0.00	Superiority
OG000 OG001	Feeling of Guilt, Hour 48:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2222	LS Mean Difference	-0.21	Standard Error of the Mean	0.173	2-Sided	95	-0.56	0.13	Superiority
OG000 OG001	Feeling of Guilt, Hour 60:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0682	LS Mean Difference	-0.29	Standard Error of the Mean	0.156	2-Sided	95	-0.60	0.02	Superiority
OG000 OG001	Feeling of Guilt, Hour 72:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0147	LS Mean Difference	-0.40	Standard Error of the Mean	0.160	2-Sided	95	-0.72	-0.08	Superiority
OG000 OG001	Feeling of Guilt, Day 7:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0837	LS Mean Difference	-0.32	Standard Error of the Mean	0.182	2-Sided	95	-0.68	0.04	Superiority
OG000 OG001	Feeling of Guilt, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5828	LS Mean Difference	-0.10	Standard Error of the Mean	0.179	2-Sided	95	-0.46	0.26	Superiority
OG000 OG001	Feeling of Guilt, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5674	LS Mean Difference	-0.10	Standard Error of the Mean	0.168	2-Sided	95	-0.43	0.24	Superiority
OG000 OG001	Feeling of Guilt, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4613	LS Mean Difference	0.11	Standard Error of the Mean	0.145	2-Sided	95	-0.18	0.40	Superiority
OG000 OG001	Suicide, Hour 2:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3240	LS Mean Difference	-0.08	Standard Error of the Mean	0.082	2-Sided	95	-0.24	0.08	Superiority
OG000 OG001	Suicide, Hour 4:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3023	LS Mean Difference	-0.08	Standard Error of the Mean	0.082	2-Sided	95	-0.24	0.08	Superiority
OG000 OG001	Suicide, Hour 8:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4127	LS Mean Difference	-0.07	Standard Error of the Mean	0.082	2-Sided	95	-0.23	0.09	Superiority
OG000 OG001	Suicide, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2819	LS Mean Difference	-0.09	Standard Error of the Mean	0.082	2-Sided	95	-0.25	0.07	Superiority
OG000 OG001	Suicide, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3884	LS Mean Difference	-0.07	Standard Error of the Mean	0.082	2-Sided	95	-0.23	0.09	Superiority
OG000 OG001	Suicide, Hour 36:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2750	LS Mean Difference	-0.09	Standard Error of the Mean	0.082	2-Sided	95	-0.25	0.07	Superiority
OG000 OG001	Suicide, Hour 48:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1811	LS Mean Difference	-0.11	Standard Error of the Mean	0.082	2-Sided	95	-0.27	0.05	Superiority
OG000 OG001	Suicide, Hour 60:MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3854	LS Mean Difference	-0.07	Standard Error of the Mean	0.082	2-Sided	95	-0.23	0.09	Superiority
OG000 OG001	Suicide, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3822	LS Mean Difference	-0.07	Standard Error of the Mean	0.082	2-Sided	95	-0.23	0.09	Superiority
OG000 OG001	Suicide, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9255	LS Mean Difference	-0.01	Standard Error of the Mean	0.082	2-Sided	95	-0.17	0.15	Superiority
OG000 OG001	Suicide, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6714	LS Mean Difference	0.04	Standard Error of the Mean	0.091	2-Sided	95	-0.14	0.22	Superiority
OG000 OG001	Suicide, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9838	LS Mean Difference	0.00	Standard Error of the Mean	0.091	2-Sided	95	-0.18	0.18	Superiority
OG000 OG001	Suicide, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8884	LS Mean Difference	-0.01	Standard Error of the Mean	0.083	2-Sided	95	-0.17	0.15	Superiority
OG000 OG001	Insomnia-Early, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6996	LS Mean Difference	-0.04	Standard Error of the Mean	0.097	2-Sided	95	-0.23	0.16	Superiority
OG000 OG001	Insomnia-Early, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4426	LS Mean Difference	0.09	Standard Error of the Mean	0.121	2-Sided	95	-0.15	0.33	Superiority
OG000 OG001	Insomnia-Early, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8743	LS Mean Difference	0.02	Standard Error of the Mean	0.110	2-Sided	95	-0.20	0.24	Superiority
OG000 OG001	Insomnia-Early, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3498	LS Mean Difference	0.11	Standard Error of the Mean	0.118	2-Sided	95	-0.12	0.35	Superiority
OG000 OG001	Insomnia-Early, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0839	LS Mean Difference	-0.26	Standard Error of the Mean	0.151	2-Sided	95	-0.56	0.04	Superiority
OG000 OG001	Insomnia-Early, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2595	LS Mean Difference	-0.18	Standard Error of the Mean	0.157	2-Sided	95	-0.49	0.13	Superiority
OG000 OG001	Insomnia-Early, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0560	LS Mean Difference	-0.32	Standard Error of the Mean	0.168	2-Sided	95	-0.66	0.01	Superiority
OG000 OG001	Insomnia-Early, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6187	LS Mean Difference	-0.09	Standard Error of the Mean	0.180	2-Sided	95	-0.45	0.27	Superiority
OG000 OG001	Insomnia-Early, Hour 72 MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0187	LS Mean Difference	-0.39	Standard Error of the Mean	0.163	2-Sided	95	-0.72	-0.07	Superiority
OG000 OG001	Insomnia-Early, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1531	LS Mean Difference	-0.26	Standard Error of the Mean	0.180	2-Sided	95	-0.62	0.10	Superiority
OG000 OG001	Insomnia-Early, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3341	LS Mean Difference	-0.19	Standard Error of the Mean	0.197	2-Sided	95	-0.58	0.20	Superiority
OG000 OG001	Insomnia-Early, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8969	LS Mean Difference	0.03	Standard Error of the Mean	0.216	2-Sided	95	-0.40	0.46	Superiority
OG000 OG001	Insomnia-Early, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5862	LS Mean Difference	0.10	Standard Error of the Mean	0.174	2-Sided	95	-0.25	0.44	Superiority
OG000 OG001	Insomnia-Middle, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3776	LS Mean Difference	0.10	Standard Error of the Mean	0.117	2-Sided	95	-0.13	0.34	Superiority
OG000 OG001	Insomnia-Middle, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9029	LS Mean Difference	-0.01	Standard Error of the Mean	0.121	2-Sided	95	-0.26	0.23	Superiority
OG000 OG001	Insomnia-Middle, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6173	LS Mean Difference	0.06	Standard Error of the Mean	0.121	2-Sided	95	-0.18	0.30	Superiority
OG000 OG001	Insomnia-Middle, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2433	LS Mean Difference	0.15	Standard Error of the Mean	0.124	2-Sided	95	-0.10	0.39	Superiority
OG000 OG001	Insomnia-Middle, Hour 24 MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0234	LS Mean Difference	-0.32	Standard Error of the Mean	0.139	2-Sided	95	-0.59	-0.04	Superiority
OG000 OG001	Insomnia-Middle, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0540	LS Mean Difference	-0.27	Standard Error of the Mean	0.139	2-Sided	95	-0.55	0.00	Superiority
OG000 OG001	Insomnia-Middle, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0406	LS Mean Difference	-0.30	Standard Error of the Mean	0.144	2-Sided	95	-0.58	-0.01	Superiority
OG000 OG001	Insomnia-Middle, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0295	LS Mean Difference	-0.29	Standard Error of the Mean	0.132	2-Sided	95	-0.56	-0.03	Superiority
OG000 OG001	Insomnia-Middle, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0925	LS Mean Difference	-0.23	Standard Error of the Mean	0.135	2-Sided	95	-0.50	0.04	Superiority
OG000 OG001	Insomnia-Middle, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1631	LS Mean Difference	-0.21	Standard Error of the Mean	0.152	2-Sided	95	-0.52	0.09	Superiority
OG000 OG001	Insomnia-Middle, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2213	LS Mean Difference	-0.23	Standard Error of the Mean	0.185	2-Sided	95	-0.60	0.14	Superiority
OG000 OG001	Insomnia-Middle, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9175	LS Mean Difference	0.02	Standard Error of the Mean	0.189	2-Sided	95	-0.36	0.39	Superiority
OG000 OG001	Insomnia-Middle, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6763	LS Mean Difference	-0.07	Standard Error of the Mean	0.165	2-Sided	95	-0.40	0.26	Superiority
OG000 OG001	Insomnia-Late, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3805	LS Mean Difference	0.11	Standard Error of the Mean	0.121	2-Sided	95	-0.13	0.35	Superiority
OG000 OG001	Insomnia-Late, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6073	LS Mean Difference	0.07	Standard Error of the Mean	0.127	2-Sided	95	-0.19	0.32	Superiority
OG000 OG001	Insomnia-Late, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.7848	LS Mean Difference	-0.03	Standard Error of the Mean	0.119	2-Sided	95	-0.27	0.20	Superiority
OG000 OG001	Insomnia-Late, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9038	LS Mean Difference	-0.01	Standard Error of the Mean	0.121	2-Sided	95	-0.25	0.23	Superiority
OG000 OG001	Insomnia-Late, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6869	LS Mean Difference	0.134	Standard Error of the Mean	0.134	2-Sided	95	-0.32	0.21	Superiority
OG000 OG001	Insomnia-Late, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9272	LS Mean Difference	0.01	Standard Error of the Mean	0.139	2-Sided	95	-0.26	0.29	Superiority
OG000 OG001	Insomnia-Late, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6931	LS Mean Difference	-0.05	Standard Error of the Mean	0.131	2-Sided	95	-0.31	0.21	Superiority
OG000 OG001	Insomnia-Late, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8262	LS Mean Difference	-0.03	Standard Error of the Mean	0.132	2-Sided	95	-0.29	0.23	Superiority
OG000 OG001	Insomnia-Late, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0749	LS Mean Difference	-0.25	Standard Error of the Mean	0.141	2-Sided	95	-0.54	0.03	Superiority
OG000 OG001	Insomnia-Late, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1923	LS Mean Difference	-0.18	Standard Error of the Mean	0.135	2-Sided	95	-0.45	0.09	Superiority
OG000 OG001	Insomnia-Late, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0326	LS Mean Difference	-0.38	Standard Error of the Mean	0.176	2-Sided	95	-0.73	-0.03	Superiority
OG000 OG001	Insomnia-Late, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4440	LS Mean Difference	-0.13	Standard Error of the Mean	0.171	2-Sided	95	-0.47	0.21	Superiority
OG000 OG001	Insomnia-Late, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.7057	LS Mean Difference	-0.05	Standard Error of the Mean	0.134	2-Sided	95	-0.32	0.22	Superiority
OG000 OG001	Work and Activities, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2865	LS Mean Difference	-0.15	Standard Error of the Mean	0.137	2-Sided	95	-0.42	0.13	Superiority
OG000 OG001	Work and Activities, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9475	LS Mean Difference	0.01	Standard Error of the Mean	0.170	2-Sided	95	-0.33	0.35	Superiority
OG000 OG001	Work and Activities, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1880	LS Mean Difference	-0.25	Standard Error of the Mean	0.185	2-Sided	95	-0.61	0.12	Superiority
OG000 OG001	Work and Activities, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5950	LS Mean Difference	-0.11	Standard Error of the Mean	0.203	2-Sided	95	-0.51	0.29	Superiority
OG000 OG001	Work and Activities, Hour 24 : MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9636	LS Mean Difference	0.01	Standard Error of the Mean	0.200	2-Sided	95	-0.39	0.41	Superiority
OG000 OG001	Work and Activities, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5836	LS Mean Difference	-0.11	Standard Error of the Mean	0.196	2-Sided	95	-0.50	0.28	Superiority
OG000 OG001	Work and Activities, Hour 48 : MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1568	LS Mean Difference	-0.26	Standard Error of the Mean	0.184	2-Sided	95	-0.63	0.10	Superiority
OG000 OG001	Work and Activities, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	Wilcoxon (Mann-Whitney)	0.0155	LS Mean Difference	-0.44	Standard Error of the Mean	0.177	2-Sided	5	-0.79	-0.09	Superiority
OG000 OG001	Work and Activities, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0504	LS Mean Difference	-0.38	Standard Error of the Mean	0.192	2-Sided	95	-0.76	0.00	Superiority
OG000 OG001	Work and Activities, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1865	LS Mean Difference	-0.28	Standard Error of the Mean	0.212	2-Sided	95	-0.70	0.14	Superiority
OG000 OG001	Work and Activities, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0518	LS Mean Difference	-0.43	Standard Error of the Mean	0.220	2-Sided	95	-0.87	0.00	Superiority
OG000 OG001	Work and Activities, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8330	LS Mean Difference	0.05	Standard Error of the Mean	0.239	2-Sided	95	-0.42	0.53	Superiority
OG000 OG001	Work and Activities, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8440	LS Mean Difference	0.04	Standard Error of the Mean	0.191	2-Sided	95	-0.34	0.42	Superiority
OG000 OG001	Retardation, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4602	LS Mean Difference	0.09	Standard Error of the Mean	0.121	2-Sided	95	-0.15	0.33	Superiority
OG000 OG001	Retardation, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0891	LS Mean Difference	0.20	Standard Error of the Mean	0.117	2-Sided	95	-0.03	0.43	Superiority
OG000 OG001	Retardation, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3088	LS Mean Difference	0.12	Standard Error of the Mean	0.117	2-Sided	95	-0.11	0.35	Superiority
OG000 OG001	Retardation, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8560	LS Mean Difference	-0.02	Standard Error of the Mean	0.112	2-Sided	95	-0.24	0.20	Superiority
OG000 OG001	Retardation, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9702	LS Mean Difference	0.00	Standard Error of the Mean	0.125	2-Sided	95	-0.24	0.25	Superiority
OG000 OG001	Retardation, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8001	LS Mean Difference	-0.03	Standard Error of the Mean	0.114	2-Sided	95	-0.25	0.20	Superiority
OG000 OG001	Retardation, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects	MMRM	0.3223	LS Mean Difference	0.11	Standard Error of the Mean	0.109	2-Sided	95	-0.11	0.32	Superiority
OG000 OG001	Retardation, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects	MMRM	0.3385	LS Mean Difference	-0.09	Standard Error of the Mean	0.089	2-Sided	95	-0.26	0.09	Superiority
OG000 OG001	Retardation, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects	MMRM	0.7003	LS Mean Difference	0.04	Standard Error of the Mean	0.100	2-Sided	95	-0.16	0.24	Superiority
OG000 OG001	Retardation, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects	MMRM	0.0311	LS Mean Difference	-0.22	Standard Error of the Mean	0.099	2-Sided	95	-0.41	-0.02	Superiority
OG000 OG001	Retardation, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects	MMRM	0.1976	LS Mean Difference	-0.10	Standard Error of the Mean	0.079	2-Sided	95	-0.26	0.06	Superiority
OG000 OG001	Retardation, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects	MMRM	0.5489	LS Mean Difference	-0.06	Standard Error of the Mean	0.092	2-Sided	95	-0.24	0.13	Superiority
OG000 OG001	Retardation, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects	MMRM	0.7992	LS Mean Difference	-0.02	Standard Error of the Mean	0.075	2-Sided	95	-0.17	0.13	Superiority
OG000 OG001	Agitation, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0573	LS Mean Difference	-0.20	Standard Error of the Mean	0.103	2-Sided	95	-0.40	0.01	Superiority
OG000 OG001	Agitation, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0431	LS Mean Difference	-0.22	Standard Error of the Mean	0.110	2-Sided	95	-0.44	-0.01	Superiority
OG000 OG001	Agitation, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0060	LS Mean Difference	-0.30	Standard Error of the Mean	0.108	2-Sided	95	-0.52	-0.09	Superiority
OG000 OG001	Agitation, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0215	LS Mean Difference	-0.30	Standard Error of the Mean	0.127	2-Sided	95	-0.55	-0.04	Superiority
OG000 OG001	Agitation, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0422	LS Mean Difference	-0.22	Standard Error of the Mean	0.109	2-Sided	95	-0.44	-0.01	Superiority
OG000 OG001	Agitation, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0433	LS Mean Difference	-0.26	Standard Error of the Mean	0.126	2-Sided	95	-0.51	-0.01	Superiority
OG000 OG001	Agitation, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0051	LS Mean Difference	-0.34	Standard Error of the Mean	0.118	2-Sided	95	-0.57	-0.10	Superiority
OG000 OG001	Agitation, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0973	LS Mean Difference	-0.22	Standard Error of the Mean	0.133	2-Sided	95	-0.48	0.04	Superiority
OG000 OG001	Agitation, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0036	LS Mean Difference	-0.38	Standard Error of the Mean	0.126	2-Sided	95	-0.63	-0.13	Superiority
OG000 OG001	Agitation, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0498	LS Mean Difference	-0.26	Standard Error of the Mean	0.131	2-Sided	95	-0.52	0.00	Superiority
OG000 OG001	Agitation, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5111	LS Mean Difference	-0.10	Standard Error of the Mean	0.147	2-Sided	95	-0.39	0.20	Superiority
OG000 OG001	Agitation, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5839	LS Mean Difference	-0.09	Standard Error of the Mean	0.155	2-Sided	95	-0.39	0.22	Superiority
OG000 OG001	Agitation, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1905	LS Mean Difference	-0.13	Standard Error of the Mean	0.100	2-Sided	95	-0.33	0.07	Superiority
OG000 OG001	Anxiety Psychic, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1767	LS Mean Difference	-0.22	Standard Error of the Mean	0.162	2-Sided	95	-0.54	0.10	Superiority
OG000 OG001	Anxiety Psychic, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5182	LS Mean Difference	-0.12	Standard Error of the Mean	0.180	2-Sided	95	-0.47	0.24	Superiority
OG000 OG001	Anxiety Psychic, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3930	LS Mean Difference	-0.16	Standard Error of the Mean	0.185	2-Sided	95	-0.53	0.21	Superiority
OG000 OG001	Anxiety Psychic, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5212	LS Mean Difference	-0.12	Standard Error of the Mean	0.189	2-Sided	95	-0.50	0.25	Superiority
OG000 OG001	Anxiety Psychic, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4741	LS Mean Difference	-0.13	Standard Error of the Mean	0.184	2-Sided	95	-0.50	0.23	Superiority
OG000 OG001	Anxiety Psychic, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4482	LS Mean Difference	-0.14	Standard Error of the Mean	0.186	2-Sided	95	-0.51	0.23	Superiority
OG000 OG001	Anxiety Psychic, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0963	LS Mean Difference	-0.31	Standard Error of the Mean	0.187	2-Sided	95	-0.69	0.06	Superiority
OG000 OG001	Anxiety Psychic, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0030	LS Mean Difference	-0.52	Standard Error of the Mean	0.171	2-Sided	95	-0.86	-0.18	Superiority
OG000 OG001	Anxiety Psychic, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1116	LS Mean Difference	-0.28	Standard Error of the Mean	0.177	2-Sided	95	-0.63	0.07	Superiority
OG000 OG001	Anxiety Psychic, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0040	LS Mean Difference	-0.51	Standard Error of the Mean	0.173	2-Sided	95	-0.86	-0.17	Superiority
OG000 OG001	Anxiety Psychic, Day 14 : MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8253	LS Mean Difference	-0.05	Standard Error of the Mean	0.244	2-Sided	95	-0.54	0.43	Superiority
OG000 OG001	Anxiety Psychic, Day 21 : MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5795	LS Mean Difference	0.12	Standard Error of the Mean	0.209	2-Sided	95	-0.30	0.53	Superiority
OG000 OG001	Anxiety Psychic, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4032	LS Mean Difference	0.15	Standard Error of the Mean	0.182	2-Sided	95	-0.21	0.51	Superiority
OG000 OG001	Anxiety Somatic, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6117	LS Mean Difference	-0.07	Standard Error of the Mean	0.133	2-Sided	95	-0.33	0.20	Superiority
OG000 OG001	Anxiety Somatic, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4716	LS Mean Difference	-0.09	Standard Error of the Mean	0.130	2-Sided	95	-0.35	0.16	Superiority
OG000 OG001	Anxiety Somatic, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6041	LS Mean Difference	-0.07	Standard Error of the Mean	0.136	2-Sided	95	-0.34	0.20	Superiority
OG000 OG001	Anxiety Somatic, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0424	LS Mean Difference	-0.27	Standard Error of the Mean	0.132	2-Sided	95	-0.53	-0.01	Superiority
OG000 OG001	Anxiety Somatic, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.7622	LS Mean Difference	-0.04	Standard Error of the Mean	0.138	2-Sided	95	-0.32	0.23	Superiority
OG000 OG001	Anxiety Somatic, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2689	LS Mean Difference	-0.14	Standard Error of the Mean	0.130	2-Sided	95	-0.40	0.11	Superiority
OG000 OG001	Anxiety Somatic, Hour 48 : MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2110	LS Mean Difference	-0.17	Standard Error of the Mean	0.134	2-Sided	95	-0.44	0.10	Superiority
OG000 OG001	Anxiety Somatic, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5873	LS Mean Difference	-0.07	Standard Error of the Mean	0.135	2-Sided	95	-0.34	0.20	Superiority
OG000 OG001	Anxiety Somatic, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0450	LS Mean Difference	-0.23	Standard Error of the Mean	0.114	2-Sided	95	-0.46	-0.01	Superiority
OG000 OG001	Anxiety Somatic, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0847	LS Mean Difference	-0.26	Standard Error of the Mean	0.152	2-Sided	95	-0.57	0.04	Superiority
OG000 OG001	Anxiety Somatic, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2522	LS Mean Difference	0.22	Standard Error of the Mean	0.189	2-Sided	95	-0.16	0.60	Superiority
OG000 OG001	Anxiety Somatic, day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5026	LS Mean Difference	-0.11	Standard Error of the Mean	0.160	2-Sided	95	-0.43	0.21	Superiority
OG000 OG001	Anxiety Somatic, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5911	LS Mean Difference	-0.08	Standard Error of the Mean	0.149	2-Sided	95	-0.38	0.22	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5800	LS Mean Difference	0.07	Standard Error of the Mean	0.122	2-Sided	95	-0.18	0.31	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6754	LS Mean Difference	-0.05	Standard Error of the Mean	0.129	2-Sided	95	-0.31	0.20	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1006	LS Mean Difference	0.19	Standard Error of the Mean	0.116	2-Sided	95	-0.04	0.42	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3588	LS Mean Difference	0.11	Standard Error of the Mean	0.120	2-Sided	95	-0.13	0.35	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5807	LS Mean Difference	-0.06	Standard Error of the Mean	0.109	2-Sided	95	-0.28	0.16	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4241	LS Mean Difference	0.09	Standard Error of the Mean	0.112	2-Sided	95	-0.13	0.31	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.7984	LS Mean Difference	-0.03	Standard Error of the Mean	0.115	2-Sided	95	-0.26	0.20	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8732	LS Mean Difference	0.02	Standard Error of the Mean	0.122	2-Sided	95	-0.22	0.26	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8621	LS Mean Difference	0.02	Standard Error of the Mean	0.107	2-Sided	95	-0.19	0.23	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1087	LS Mean Difference	-0.20	Standard Error of the Mean	0.126	2-Sided	95	-0.45	0.05	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2153	LS Mean Difference	-0.16	Standard Error of the Mean	0.125	2-Sided	95	-0.41	0.09	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1422	LS Mean Difference	-0.22	Standard Error of the Mean	0.145	2-Sided	95	-0.51	0.07	Superiority
OG000 OG001	Somatic Symptoms Gastrointestinal, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.7211	LS Mean Difference	0.04	Standard Error of the Mean	0.114	2-Sided	95	-0.19	0.27	Superiority
OG000 OG001	Somatic Symptoms General, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8224	LS Mean Difference	0.02	Standard Error of the Mean	0.103	2-Sided	95	-0.18	0.23	Superiority
OG000 OG001	Somatic Symptoms General, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6362	LS Mean Difference	-0.06	Standard Error of the Mean	0.126	2-Sided	95	-0.31	0.19	Superiority
OG000 OG001	Somatic Symptoms General, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6094	LS Mean Difference	-0.06	Standard Error of the Mean	0.123	2-Sided	95	-0.31	0.18	Superiority
OG000 OG001	Somatic Symptoms General, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0457	LS Mean Difference	-0.25	Standard Error of the Mean	0.123	2-Sided	95	-0.49	0.00	Superiority
OG000 OG001	Somatic Symptoms General, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5691	LS Mean Difference	-0.08	Standard Error of the Mean	0.140	2-Sided	95	-0.36	0.20	Superiority
OG000	Somatic Symptoms General, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2942	LS Mean Difference	-0.14	Standard Error of the Mean	0.130	2-Sided	95	-0.40	0.12	Superiority
OG000 OG001	Somatic Symptoms General, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5389	LS Mean Difference	-0.08	Standard Error of the Mean	0.136	2-Sided	95	-0.35	0.19	Superiority
OG000 OG001	Somatic Symptoms General, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4061	LS Mean Difference	-0.12	Standard Error of the Mean	0.141	2-Sided	95	-0.40	0.16	Superiority
OG000 OG001	Somatic Symptoms General, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0990	LS Mean Difference	-0.25	Standard Error of the Mean	0.153	2-Sided	95	-0.56	0.05	Superiority
OG000 OG001	Somatic Symptoms General, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0108	LS Mean Difference	-0.36	Standard Error of the Mean	0.138	2-Sided	95	-0.63	-0.08	Superiority
OG000 OG001	Somatic Symptoms General, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0889	LS Mean Difference	-0.28	Standard Error of the Mean	0.160	2-Sided	95	-0.59	0.04	Superiority
OG000 OG001	Somatic Symptoms General, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3721	LS Mean Difference	0.15	Standard Error of the Mean	0.169	2-Sided	95	-0.18	0.49	Superiority
OG000 OG001	Somatic Symptoms General, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5513	LS Mean Difference	-0.08	Standard Error of the Mean	0.141	2-Sided	95	-0.36	0.20	Superiority
OG000 OG001	Genital Symptoms, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0748	LS Mean Difference	0.12	Standard Error of the Mean	0.067	2-Sided	95	-0.01	0.26	Superiority
OG000 OG001	Genital Symptoms, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3545	LS Mean Difference	0.08	Standard Error of the Mean	0.087	2-Sided	95	-0.09	0.25	Superiority
OG000 OG001	Genital Symptoms, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6531	LS Mean Difference	0.04	Standard Error of the Mean	0.094	2-Sided	95	-0.14	0.23	Superiority
OG000 OG001	Genital Symptoms, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.7520	LS Mean Difference	-0.04	Standard Error of the Mean	0.115	2-Sided	95	-0.26	0.19	Superiority
OG000 OG001	Genital Symptoms, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8861	LS Mean Difference	-0.02	Standard Error of the Mean	0.123	2-Sided	95	-0.26	0.23	Superiority
OG000 OG001	Genital Symptoms, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3280	LS Mean Difference	-0.12	Standard Error of the Mean	0.127	2-Sided	95	-0.38	0.13	Superiority
OG000 OG001	Genital Symptoms, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1123	LS Mean Difference	-0.21	Standard Error of the Mean	0.128	2-Sided	95	-0.46	0.05	Superiority
OG000 OG001	Genital Symptoms, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2541	LS Mean Difference	-0.13	Standard Error of the Mean	0.116	2-Sided	95	-0.36	0.10	Superiority
OG000 OG001	Genital Symptoms, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0110	LS Mean Difference	-0.37	Standard Error of the Mean	0.143	2-Sided	95	-0.66	-0.09	Superiority
OG000 OG001	Genital Symptoms, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.7720	LS Mean Difference	-0.05	Standard Error of the Mean	0.158	2-Sided	95	-0.36	0.27	Superiority
OG000 OG001	Genital Symptoms, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6311	LS Mean Difference	-0.10	Standard Error of the Mean	0.210	2-Sided	95	-0.52	0.32	Superiority
OG000 OG001	Genital Symptoms, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6877	LS Mean Difference	-0.08	Standard Error of the Mean	0.207	2-Sided	95	-0.50	0.33	Superiority
OG000 OG001	Genital Symptoms, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2465	LS Mean Difference	0.22	Standard Error of the Mean	0.186	2-Sided	95	-0.15	0.58	Superiority
OG000 OG001	Hypochondriasis, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1279	LS Mean Difference	-0.16	Standard Error of the Mean	0.101	2-Sided	95	-0.36	0.05	Superiority
OG000 OG001	Hypochondriasis, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3946	LS Mean Difference	-0.08	Standard Error of the Mean	0.093	2-Sided	95	-0.26	0.10	Superiority
OG000 OG001	Hypochondriasis, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6694	LS Mean Difference	-0.04	Standard Error of the Mean	0.095	2-Sided	95	-0.23	0.15	Superiority
OG000 OG001	Hypochondriasis, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1113	LS Mean Difference	-0.16	Standard Error of the Mean	0.100	2-Sided	95	-0.36	0.04	Superiority
OG000 OG001	Hypochondriasis, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5811	LS Mean Difference	0.05	Standard Error of the Mean	0.089	2-Sided	95	-0.13	0.23	Superiority
OG000 OG001	Hypochondriasis, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6794	LS Mean Difference	-0.04	Standard Error of the Mean	0.106	2-Sided	95	-0.25	0.17	Superiority
OG000 OG001	Hypochondriasis, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6031	LS Mean Difference	0.05	Standard Error of the Mean	0.099	2-Sided	95	-0.14	0.25	Superiority
OG000 OG001	Hypochondriasis, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6673	LS Mean Difference	-0.04	Standard Error of the Mean	0.099	2-Sided	95	-0.24	0.15	Superiority
OG000 OG001	Hypochondriasis, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6472	LS Mean Difference	-0.05	Standard Error of the Mean	0.102	2-Sided	95	-0.25	0.16	Superiority
OG000 OG001	Hypochondriasis, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8654	LS Mean Difference	-0.02	Standard Error of the Mean	0.119	2-Sided	95	-0.26	0.22	Superiority
OG000 OG001	Hypochondriasis, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2101	LS Mean Difference	-0.18	Standard Error of the Mean	0.140	2-Sided	95	-0.48	0.11	Superiority
OG000 OG001	Hypochondriasis, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.7128	LS Mean Difference	-0.05	Standard Error of the Mean	0.126	2-Sided	95	-0.30	0.21	Superiority
OG000 OG001	Hypochondriasis, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3297	LS Mean Difference	-0.09	Standard Error of the Mean	0.090	2-Sided	95	-0.27	0.09	Superiority
OG000 OG001	Loss of weight, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4493	LS Mean Difference	0.05	Standard Error of the Mean	0.069	2-Sided	95	-0.08	0.19	Superiority
OG000 OG001	Loss of weight, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0717	LS Mean Difference	0.15	Standard Error of the Mean	0.081	2-Sided	95	-0.01	0.31	Superiority
OG000 OG001	Loss of Weight, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1054	LS Mean Difference	0.11	Standard Error of the Mean	0.066	2-Sided	95	-0.02	0.24	Superiority
OG000 OG001	Loss of Weight, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0408	LS Mean Difference	0.18	Standard Error of the Mean	0.088	2-Sided	95	0.01	0.36	Superiority
OG000 OG001	Loss of Weight, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0233	LS Mean Difference	0.20	Standard Error of the Mean	0.088	2-Sided	95	0.03	0.38	Superiority
OG000 OG001	Loss of Weight, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3610	LS Mean Difference	0.08	Standard Error of the Mean	0.088	2-Sided	95	-0.09	0.26	Superiority
OG000 OG001	Loss of Weight, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2358	LS Mean Difference	0.12	Standard Error of the Mean	0.100	2-Sided	95	-0.08	0.32	Superiority
OG000 OG001	Loss of Weight, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9492	LS Mean Difference	0.01	Standard Error of the Mean	0.085	2-Sided	95	-0.16	0.17	Superiority
OG000 OG001	Loss of Weight, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.4352	LS Mean Difference	-0.08	Standard Error of the Mean	0.102	2-Sided	95	-0.28	0.12	Superiority
OG000 OG001	Loss of Weight, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1176	LS Mean Difference	0.20	Standard Error of the Mean	0.125	2-Sided	95	-0.05	0.44	Superiority
OG000 OG001	Loss of Weight, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.7812	LS Mean Difference	0.05	Standard Error of the Mean	0.174	2-Sided	95	-0.30	0.40	Superiority
OG000 OG001	Loss of Weight, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.5085	LS Mean Difference	-0.12	Standard Error of the Mean	0.182	2-Sided	95	-0.48	0.24	Superiority
OG000 OG001	Loss of Weight, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8274	LS Mean Difference	0.03	Standard Error of the Mean	0.156	2-Sided	95	-0.28	0.34	Superiority
OG000 OG001	Insight, Hour 2: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3675	LS Mean Difference	-0.04	Standard Error of the Mean	0.045	2-Sided	95	-0.13	0.05	Superiority
OG000 OG001	Insight, Hour 4: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1818	LS Mean Difference	-0.06	Standard Error of the Mean	0.045	2-Sided	95	-0.15	0.03	Superiority
OG000 OG001	Insight, Hour 8: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.0826	LS Mean Difference	-0.08	Standard Error of the Mean	0.045	2-Sided	95	-0.17	0.01	Superiority
OG000 OG001	Insight, Hour 12: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6436	LS Mean Difference	-0.02	Standard Error of the Mean	0.045	2-Sided	95	-0.11	0.07	Superiority
OG000 OG001	Insight, Hour 24: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.1827	LS Mean Difference	-0.06	Standard Error of the Mean	0.045	2-Sided	95	-0.15	0.03	Superiority
OG000 OG001	Insight, Hour 36: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9859	LS Mean Difference	0.00	Standard Error of the Mean	0.045	2-Sided	95	-0.09	0.09	Superiority
OG000 OG001	Insight, Hour 48: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6672	LS Mean Difference	0.02	Standard Error of the Mean	0.045	2-Sided	95	-0.07	0.11	Superiority
OG000 OG001	Insight, Hour 60: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.2031	LS Mean Difference	0.06	Standard Error of the Mean	0.046	2-Sided	95	-0.03	0.15	Superiority
OG000 OG001	Insight, Hour 72: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6664	LS Mean Difference	0.02	Standard Error of the Mean	0.045	2-Sided	95	-0.07	0.11	Superiority
OG000 OG001	Insight, Day 7: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.3417	LS Mean Difference	-0.04	Standard Error of the Mean	0.045	2-Sided	95	-0.13	0.05	Superiority
OG000 OG001	Insight, Day 14: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.6622	LS Mean Difference	-0.02	Standard Error of the Mean	0.051	2-Sided	95	-0.12	0.08	Superiority
OG000 OG001	Insight, Day 21: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.9087	LS Mean Difference	-0.01	Standard Error of the Mean	0.051	2-Sided	95	-0.11	0.09	Superiority
OG000 OG001	Insight, Day 30: MMRM was used for analysis. The change from baseline in HAM-D individual item score at each visit was the dependent variable. Treatment, baseline HAM-D individual item score, pooled center, baseline antidepressant use, visit time point, and visit time point-by-treatment interaction terms were explanatory variables included in the model. All explanatory variables including pooled center were treated as fixed effects.	MMRM	0.8263	LS Mean Difference	0.01	Standard Error of the Mean	0.046	2-Sided	95	-0.08	0.10	Superiority

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Altered state of consciousness	Nervous system disorders	MedDRA 19.1	Systematic Assessment		EG0000 affected53 at risk EG0011 affected51 at risk
Syncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment		EG0000 affected53 at risk EG0011 affected51 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected53 at risk EG0015 affected51 at risk
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected53 at risk EG0013 affected51 at risk
Infusion site pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected53 at risk EG0015 affected51 at risk
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0004 affected53 at risk EG0015 affected51 at risk
Headache	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0006 affected53 at risk EG0019 affected51 at risk
Somnolence	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected53 at risk EG0014 affected51 at risk

ID	Term
D011644	Puerperal Disorders
D011248	Pregnancy Complications
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders

ID	Title	Description
BG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.
BG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received an infusion rate equivalent to the 90 μg/kg/h group.	0	53	0	53	13	53
EG001	SAGE-547 90 μg/kg/h	Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).	0	51	1	51	21	51