Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of SAGE-547 in Participants With Severe Postpartum Depression (547-PPD-202B) (NCT NCT02942004)

NCT ID: NCT02942004

Last Updated: 2025-10-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

138 participants

Primary outcome timeframe

Baseline, Hour 60

Results posted on

2025-10-14

Participant Flow

Participants took part in the study at 32 centers in United States from 01 August 2016 to 19 October 2017.

A total of 138 participants were randomized into the study to receive either placebo or SAGE-547. Forty-three received placebo, and 79 received SAGE-547.

Participant milestones

Participant milestones
Measure	Placebo Participants received infusion rates equivalent to either the 60 micrograms per kilogram per hour (μg/kg/h) or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	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).
Overall Study STARTED	46	47	45
Overall Study Participants Who Received Study Drug	43	38	41
Overall Study COMPLETED	42	35	36
Overall Study NOT COMPLETED	4	12	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received infusion rates equivalent to either the 60 micrograms per kilogram per hour (μg/kg/h) or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	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).
Overall Study Withdrawal by Subject	0	2	3
Overall Study Lost to Follow-up	1	1	2
Overall Study Randomized but not dosed	3	9	4

Baseline Characteristics

A Study to Evaluate Efficacy and Safety of SAGE-547 in Participants With Severe Postpartum Depression (547-PPD-202B)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).	Total n=122 Participants Total of all reporting groups
Age, Continuous	27.2 years STANDARD_DEVIATION 6.13 • n=5 Participants	27.7 years STANDARD_DEVIATION 6.46 • n=7 Participants	27.5 years STANDARD_DEVIATION 6.05 • n=5 Participants	27.4 years STANDARD_DEVIATION 6.16 • n=4 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	38 Participants n=7 Participants	41 Participants n=5 Participants	122 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	15 Participants n=5 Participants	12 Participants n=7 Participants	8 Participants n=5 Participants	35 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian & Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized White	27 Participants n=5 Participants	25 Participants n=7 Participants	29 Participants n=5 Participants	81 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latina	7 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	17 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latina	36 Participants n=5 Participants	35 Participants n=7 Participants	34 Participants n=5 Participants	105 Participants n=4 Participants
Hamilton Rating Scale for Depression (HAM-D) Total Score	28.6 score on a scale STANDARD_DEVIATION 2.54 • n=5 Participants	29.0 score on a scale STANDARD_DEVIATION 2.70 • n=7 Participants	28.4 score on a scale STANDARD_DEVIATION 2.47 • n=5 Participants	28.7 score on a scale STANDARD_DEVIATION 2.55 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Hour 60

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=37 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=39 Participants 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).
Change From Baseline at 60 Hours in the 17-Item Hamilton Rating Scale for Depression (HAM-D) Total Score	-14.04 score on a scale Standard Error 1.148	-19.54 score on a scale Standard Error 1.231	-17.72 score on a scale Standard Error 1.193

SECONDARY outcome

Timeframe: Baseline, Day 30

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=35 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=36 Participants 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).
Change From Baseline in HAM-D Total Score at Day 30	-13.82 score on a scale Standard Error 1.324	-19.45 score on a scale Standard Error 1.435	-17.62 score on a scale Standard Error 1.400

SECONDARY outcome

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

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).
Change From Baseline in HAM-D Total Score Change at Hour 2	-5.04 score on a scale Standard Error 0.669	-4.99 score on a scale Standard Error 0.721	-4.89 score on a scale Standard Error 0.707
Change From Baseline in HAM-D Total Score Change at Hour 4	-6.88 score on a scale Standard Error 0.841	-8.99 score on a scale Standard Error 0.902	-7.18 score on a scale Standard Error 0.879
Change From Baseline in HAM-D Total Score Change at Hour 8	-8.13 score on a scale Standard Error 0.928	-10.18 score on a scale Standard Error 0.994	-8.50 score on a scale Standard Error 0.966
Change From Baseline in HAM-D Total Score Change at Hour 12	-9.79 score on a scale Standard Error 0.992	-11.04 score on a scale Standard Error 1.069	-9.07 score on a scale Standard Error 1.034
Change From Baseline in HAM-D Total Score Change at Hour 24	-10.71 score on a scale Standard Error 1.121	-15.00 score on a scale Standard Error 1.199	-13.03 score on a scale Standard Error 1.157
Change From Baseline in HAM-D Total Score Change at Hour 36	-12.58 score on a scale Standard Error 1.114	-17.69 score on a scale Standard Error 1.203	-13.93 score on a scale Standard Error 1.157
Change From Baseline in HAM-D Total Score Change at Hour 48	-13.55 score on a scale Standard Error 1.195	-18.04 score on a scale Standard Error 1.282	-16.89 score on a scale Standard Error 1.239
Change From Baseline in HAM-D Total Score Change at Hour 72	-14.67 score on a scale Standard Error 1.197	-19.69 score on a scale Standard Error 1.285	-17.19 score on a scale Standard Error 1.243
Change From Baseline in HAM-D Total Score Change at Day 7	-13.34 score on a scale Standard Error 1.268	-17.41 score on a scale Standard Error 1.353	-14.93 score on a scale Standard Error 1.315
Change From Baseline in HAM-D Total Score Change at Day 14	-14.64 score on a scale Standard Error 1.457	-17.56 score on a scale Standard Error 1.586	-15.64 score on a scale Standard Error 1.521
Change From Baseline in HAM-D Total Score Change at Day 21	-13.23 score on a scale Standard Error 1.380	-18.15 score on a scale Standard Error 1.529	-16.74 score on a scale Standard Error 1.451

SECONDARY outcome

Timeframe: Hour 60, Days 7 and 30

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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).
Percentage of Participants With HAM-D Response Hour 60	55.8 percentage of participants	86.5 percentage of participants	74.4 percentage of participants
Percentage of Participants With HAM-D Response Day 7	48.8 percentage of participants	68.4 percentage of participants	52.5 percentage of participants
Percentage of Participants With HAM-D Response Day 30	50.0 percentage of participants	82.9 percentage of participants	69.4 percentage of participants

SECONDARY outcome

Timeframe: Hour 60, Days 7 and 30

The 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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).
Percentage of Participants With HAM-D Remission Hour 60	16.3 percentage of participants	51.4 percentage of participants	30.8 percentage of participants
Percentage of Participants With HAM-D Remission Day 7	30.2 percentage of participants	31.6 percentage of participants	20.0 percentage of participants
Percentage of Participants With HAM-D Remission Day 30	31.0 percentage of participants	48.6 percentage of participants	38.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Hour 60, Days 7 and 30

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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).
Change From Baseline in HAM-D Bech 6 Subscale Hour 60	-32.60 score on a scale Standard Error 2.962	-44.67 score on a scale Standard Error 3.178	-38.49 score on a scale Standard Error 3.081
Change From Baseline in HAM-D Bech 6 Subscale Day 7	-29.43 score on a scale Standard Error 3.116	-38.52 score on a scale Standard Error 3.327	-31.67 score on a scale Standard Error 3.236
Change From Baseline in HAM-D Bech 6 Subscale Day 30	-30.94 score on a scale Standard Error 3.122	-42.62 score on a scale Standard Error 3.385	-39.20 score on a scale Standard Error 3.304

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Hour 2	-0.54 score on a scale Standard Error 0.133	-0.54 score on a scale Standard Error 0.143	-0.45 score on a scale Standard Error 0.139
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Hour 4	-0.79 score on a scale Standard Error 0.165	-0.97 score on a scale Standard Error 0.176	-0.79 score on a scale Standard Error 0.171
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Hour 8	-1.02 score on a scale Standard Error 0.166	-1.23 score on a scale Standard Error 0.178	-0.94 score on a scale Standard Error 0.172
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Hour 12	-1.33 score on a scale Standard Error 0.170	-1.50 score on a scale Standard Error 0.184	-1.15 score on a scale Standard Error 0.177
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Hour 24	-1.40 score on a scale Standard Error 0.163	-1.40 score on a scale Standard Error 0.175	-1.47 score on a scale Standard Error 0.169
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Hour 36	-1.47 score on a scale Standard Error 0.170	-2.03 score on a scale Standard Error 0.184	-1.49 score on a scale Standard Error 0.176
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Hour 48	-1.58 score on a scale Standard Error 0.173	-2.07 score on a scale Standard Error 0.186	-1.84 score on a scale Standard Error 0.180
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Hour 60	-1.56 score on a scale Standard Error 0.169	-2.27 score on a scale Standard Error 0.181	-1.92 score on a scale Standard Error 0.176
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Hour 72	-1.75 score on a scale Standard Error 0.162	-2.32 score on a scale Standard Error 0.174	-1.97 score on a scale Standard Error 0.169
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Day 7	-1.49 score on a scale Standard Error 0.170	-1.94 score on a scale Standard Error 0.182	-1.55 score on a scale Standard Error 0.177
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Day 14	-1.53 score on a scale Standard Error 0.205	-2.06 score on a scale Standard Error 0.225	-1.65 score on a scale Standard Error 0.213
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Day 21	-1.48 score on a scale Standard Error 0.204	-1.79 score on a scale Standard Error 0.229	-1.75 score on a scale Standard Error 0.214
Change From Baseline in HAM-D Individual Item Scores Depressed Mood, Change at Day 30	-1.53 score on a scale Standard Error 0.170	-2.19 score on a scale Standard Error 0.186	-1.97 score on a scale Standard Error 0.183
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Hour 2	-0.46 score on a scale Standard Error 0.133	-0.54 score on a scale Standard Error 0.143	-0.40 score on a scale Standard Error 0.138
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Hour 4	-0.70 score on a scale Standard Error 0.157	-1.12 score on a scale Standard Error 0.168	-0.84 score on a scale Standard Error 0.162
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Hour 8	-0.84 score on a scale Standard Error 0.162	-1.25 score on a scale Standard Error 0.173	-0.94 score on a scale Standard Error 0.168
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Hour 12	-1.04 score on a scale Standard Error 0.164	-1.25 score on a scale Standard Error 0.178	-0.76 score on a scale Standard Error 0.171
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Hour 24	-1.04 score on a scale Standard Error 0.162	-1.50 score on a scale Standard Error 0.173	-1.03 score on a scale Standard Error 0.167
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Hour 36	-1.23 score on a scale Standard Error 0.150	-1.59 score on a scale Standard Error 0.162	-1.26 score on a scale Standard Error 0.156
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Hour 48	-1.25 score on a scale Standard Error 0.152	-1.64 score on a scale Standard Error 0.163	-1.60 score on a scale Standard Error 0.158
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Hour 60	-1.23 score on a scale Standard Error 0.149	-1.68 score on a scale Standard Error 0.160	-1.63 score on a scale Standard Error 0.155
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Hour 72	-1.42 score on a scale Standard Error 0.145	-1.69 score on a scale Standard Error 0.157	-1.57 score on a scale Standard Error 0.152
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Day 7	-1.18 score on a scale Standard Error 0.152	-1.38 score on a scale Standard Error 0.163	-1.36 score on a scale Standard Error 0.159
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Day 14	-1.33 score on a scale Standard Error 0.158	-1.49 score on a scale Standard Error 0.173	-1.56 score on a scale Standard Error 0.169
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Hour 12	-0.92 score on a scale Standard Error 0.089	-0.89 score on a scale Standard Error 0.096	-0.66 score on a scale Standard Error 0.092
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Day 21	-1.10 score on a scale Standard Error 0.162	-1.51 score on a scale Standard Error 0.181	-1.51 score on a scale Standard Error 0.171
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Hour 24	-0.87 score on a scale Standard Error 0.086	-0.96 score on a scale Standard Error 0.092	-0.68 score on a scale Standard Error 0.088
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt, Change at Day 30	-1.40 score on a scale Standard Error 0.149	-1.61 score on a scale Standard Error 0.163	-1.62 score on a scale Standard Error 0.161
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Day 7	-0.69 score on a scale Standard Error 0.144	-1.20 score on a scale Standard Error 0.154	-0.97 score on a scale Standard Error 0.150
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Day 14	-0.97 score on a scale Standard Error 0.174	-1.19 score on a scale Standard Error 0.192	-1.06 score on a scale Standard Error 0.182
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Day 21	-0.69 score on a scale Standard Error 0.154	-1.28 score on a scale Standard Error 0.173	-1.11 score on a scale Standard Error 0.160
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Day 30	-0.67 score on a scale Standard Error 0.141	-1.34 score on a scale Standard Error 0.155	-1.09 score on a scale Standard Error 0.153
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Hour 2	-0.13 score on a scale Standard Error 0.073	0.03 score on a scale Standard Error 0.078	-0.17 score on a scale Standard Error 0.076
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Hour 4	-0.16 score on a scale Standard Error 0.096	-0.21 score on a scale Standard Error 0.102	-0.24 score on a scale Standard Error 0.099
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Hour 8	-0.20 score on a scale Standard Error 0.099	-0.16 score on a scale Standard Error 0.105	-0.32 score on a scale Standard Error 0.102
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Hour 12	-0.16 score on a scale Standard Error 0.091	-0.18 score on a scale Standard Error 0.098	-0.22 score on a scale Standard Error 0.095
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Hour 2	-0.57 score on a scale Standard Error 0.101	-0.87 score on a scale Standard Error 0.107	-0.48 score on a scale Standard Error 0.104
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Hour 4	-0.64 score on a scale Standard Error 0.098	-0.92 score on a scale Standard Error 0.105	-0.61 score on a scale Standard Error 0.101
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Hour 8	-0.81 score on a scale Standard Error 0.088	-1.00 score on a scale Standard Error 0.094	-0.63 score on a scale Standard Error 0.091
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Hour 36	-0.90 score on a scale Standard Error 0.068	-1.00 score on a scale Standard Error 0.074	-0.75 score on a scale Standard Error 0.071
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Hour 48	-0.88 score on a scale Standard Error 0.063	-0.94 score on a scale Standard Error 0.069	-0.95 score on a scale Standard Error 0.066
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Hour 60	-0.81 score on a scale Standard Error 0.065	-1.03 score on a scale Standard Error 0.071	-0.98 score on a scale Standard Error 0.069
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Hour 72	-0.88 score on a scale Standard Error 0.068	-1.01 score on a scale Standard Error 0.074	-0.90 score on a scale Standard Error 0.071
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Day 7	-0.71 score on a scale Standard Error 0.089	-0.90 score on a scale Standard Error 0.095	-0.77 score on a scale Standard Error 0.093
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Day 14	-0.92 score on a scale Standard Error 0.084	-0.99 score on a scale Standard Error 0.093	-0.80 score on a scale Standard Error 0.090
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Day 21	-0.61 score on a scale Standard Error 0.133	-0.80 score on a scale Standard Error 0.152	-0.88 score on a scale Standard Error 0.141
Change From Baseline in HAM-D Individual Item Scores Suicide, Change at Day 30	-0.76 score on a scale Standard Error 0.080	-0.99 score on a scale Standard Error 0.088	-0.88 score on a scale Standard Error 0.086
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Hour 24	-0.57 score on a scale Standard Error 0.135	-0.98 score on a scale Standard Error 0.145	-0.93 score on a scale Standard Error 0.139
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Hour 36	-0.74 score on a scale Standard Error 0.130	-1.03 score on a scale Standard Error 0.141	-1.02 score on a scale Standard Error 0.135
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Hour 48	-0.90 score on a scale Standard Error 0.132	-1.17 score on a scale Standard Error 0.142	-1.19 score on a scale Standard Error 0.137
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Hour 60	-0.83 score on a scale Standard Error 0.130	-1.22 score on a scale Standard Error 0.140	-1.23 score on a scale Standard Error 0.135
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Hour 72	-0.93 score on a scale Standard Error 0.132	-1.22 score on a scale Standard Error 0.143	-1.09 score on a scale Standard Error 0.138
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Day 7	-0.95 score on a scale Standard Error 0.128	-1.05 score on a scale Standard Error 0.136	-0.87 score on a scale Standard Error 0.133
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Day 14	-0.72 score on a scale Standard Error 0.146	-1.36 score on a scale Standard Error 0.161	-0.98 score on a scale Standard Error 0.154
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Day 21	-0.77 score on a scale Standard Error 0.146	-1.27 score on a scale Standard Error 0.164	-0.90 score on a scale Standard Error 0.152
Change From Baseline in HAM-D Individual Item Scores Insomnia - Middle, Change at Day 30	-0.78 score on a scale Standard Error 0.134	-1.21 score on a scale Standard Error 0.147	-0.99 score on a scale Standard Error 0.144
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Hour 2	-0.16 score on a scale Standard Error 0.090	0.01 score on a scale Standard Error 0.096	-0.22 score on a scale Standard Error 0.094
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Hour 4	-0.16 score on a scale Standard Error 0.104	-0.12 score on a scale Standard Error 0.111	-0.34 score on a scale Standard Error 0.108
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Hour 8	-0.14 score on a scale Standard Error 0.103	-0.20 score on a scale Standard Error 0.110	-0.37 score on a scale Standard Error 0.106
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Hour 12	-0.16 score on a scale Standard Error 0.103	-0.01 score on a scale Standard Error 0.111	-0.31 score on a scale Standard Error 0.107
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Hour 24	-0.68 score on a scale Standard Error 0.123	-0.94 score on a scale Standard Error 0.133	-0.95 score on a scale Standard Error 0.127
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Hour 36	-0.75 score on a scale Standard Error 0.127	-0.91 score on a scale Standard Error 0.139	-0.90 score on a scale Standard Error 0.132
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Hour 48	-0.89 score on a scale Standard Error 0.125	-1.16 score on a scale Standard Error 0.135	-1.15 score on a scale Standard Error 0.130
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Hour 60	-0.89 score on a scale Standard Error 0.121	-1.16 score on a scale Standard Error 0.130	-1.22 score on a scale Standard Error 0.126
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Hour 72	-1.07 score on a scale Standard Error 0.121	-1.13 score on a scale Standard Error 0.131	-1.12 score on a scale Standard Error 0.126
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Day 7	-0.89 score on a scale Standard Error 0.126	-0.80 score on a scale Standard Error 0.135	-1.04 score on a scale Standard Error 0.132
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Day 14	-0.79 score on a scale Standard Error 0.155	-0.96 score on a scale Standard Error 0.172	-0.86 score on a scale Standard Error 0.164
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Day 21	-0.77 score on a scale Standard Error 0.157	-0.89 score on a scale Standard Error 0.176	-0.74 score on a scale Standard Error 0.164
Change From Baseline in HAM-D Individual Item Scores Insomnia - Late, Change at Day 30	-0.77 score on a scale Standard Error 0.130	-1.03 score on a scale Standard Error 0.143	-1.09 score on a scale Standard Error 0.140
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Hour 2	-0.30 score on a scale Standard Error 0.105	-0.43 score on a scale Standard Error 0.113	-0.25 score on a scale Standard Error 0.111
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Hour 4	-0.51 score on a scale Standard Error 0.126	-0.74 score on a scale Standard Error 0.135	-0.43 score on a scale Standard Error 0.131
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Hour 8	-0.81 score on a scale Standard Error 0.160	-0.95 score on a scale Standard Error 0.170	-0.67 score on a scale Standard Error 0.165
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Hour 12	-1.02 score on a scale Standard Error 0.160	-1.20 score on a scale Standard Error 0.173	-0.83 score on a scale Standard Error 0.166
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Hour 24	-1.07 score on a scale Standard Error 0.169	-1.19 score on a scale Standard Error 0.180	-1.04 score on a scale Standard Error 0.174
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Hour 36	-1.39 score on a scale Standard Error 0.162	-1.77 score on a scale Standard Error 0.176	-1.09 score on a scale Standard Error 0.168
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Hour 48	-1.51 score on a scale Standard Error 0.179	-1.80 score on a scale Standard Error 0.192	-1.57 score on a scale Standard Error 0.185
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Hour 60	-1.46 score on a scale Standard Error 0.171	-2.04 score on a scale Standard Error 0.184	-1.70 score on a scale Standard Error 0.178
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Hour 72	-1.67 score on a scale Standard Error 0.164	-2.18 score on a scale Standard Error 0.177	-1.67 score on a scale Standard Error 0.171
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Day 7	-1.39 score on a scale Standard Error 0.176	-1.82 score on a scale Standard Error 0.187	-1.57 score on a scale Standard Error 0.182
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Day 14	-1.58 score on a scale Standard Error 0.198	-1.57 score on a scale Standard Error 0.218	-1.60 score on a scale Standard Error 0.208
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Day 21	-1.35 score on a scale Standard Error 0.191	-1.96 score on a scale Standard Error 0.214	-1.87 score on a scale Standard Error 0.200
Change From Baseline in HAM-D Individual Item Scores Work and Activities, Change at Day 30	-1.55 score on a scale Standard Error 0.174	-2.08 score on a scale Standard Error 0.189	-1.93 score on a scale Standard Error 0.185
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Hour 2	-0.18 score on a scale Standard Error 0.084	0.17 score on a scale Standard Error 0.090	-0.01 score on a scale Standard Error 0.087
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Hour 4	-0.34 score on a scale Standard Error 0.090	-0.02 score on a scale Standard Error 0.096	-0.03 score on a scale Standard Error 0.093
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Hour 8	-0.36 score on a scale Standard Error 0.092	-0.20 score on a scale Standard Error 0.098	-0.16 score on a scale Standard Error 0.095
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Hour 12	-0.57 score on a scale Standard Error 0.099	-0.47 score on a scale Standard Error 0.107	-0.42 score on a scale Standard Error 0.103
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Hour 24	-0.48 score on a scale Standard Error 0.092	-0.47 score on a scale Standard Error 0.099	-0.47 score on a scale Standard Error 0.095
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Hour 36	-0.71 score on a scale Standard Error 0.103	-0.87 score on a scale Standard Error 0.112	-0.65 score on a scale Standard Error 0.107
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Hour 48	-0.57 score on a scale Standard Error 0.098	-0.70 score on a scale Standard Error 0.105	-0.60 score on a scale Standard Error 0.101
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Hour 60	-0.76 score on a scale Standard Error 0.090	-0.84 score on a scale Standard Error 0.097	-0.74 score on a scale Standard Error 0.094
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Hour 72	-0.67 score on a scale Standard Error 0.092	-0.87 score on a scale Standard Error 0.099	-0.80 score on a scale Standard Error 0.096
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Day 7	-0.67 score on a scale Standard Error 0.091	-1.02 score on a scale Standard Error 0.097	-0.70 score on a scale Standard Error 0.095
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Day 14	-0.74 score on a scale Standard Error 0.117	-0.87 score on a scale Standard Error 0.128	-0.77 score on a scale Standard Error 0.123
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Day 21	-0.72 score on a scale Standard Error 0.104	-1.05 score on a scale Standard Error 0.115	-0.81 score on a scale Standard Error 0.108
Change From Baseline in HAM-D Individual Item Scores Retardation, Change at Day 30	-0.66 score on a scale Standard Error 0.088	-1.08 score on a scale Standard Error 0.096	-0.91 score on a scale Standard Error 0.095
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Hour 2	-0.46 score on a scale Standard Error 0.108	-0.52 score on a scale Standard Error 0.115	-0.45 score on a scale Standard Error 0.111
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Hour 4	-0.56 score on a scale Standard Error 0.103	-0.70 score on a scale Standard Error 0.109	-0.52 score on a scale Standard Error 0.106
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Hour 8	-0.51 score on a scale Standard Error 0.112	-0.68 score on a scale Standard Error 0.119	-0.55 score on a scale Standard Error 0.116
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Hour 60	-0.58 score on a scale Standard Error 0.105	-0.85 score on a scale Standard Error 0.113	-0.70 score on a scale Standard Error 0.110
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Hour 12	-0.56 score on a scale Standard Error 0.114	-0.65 score on a scale Standard Error 0.123	-0.59 score on a scale Standard Error 0.118
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Hour 24	-0.54 score on a scale Standard Error 0.108	-0.86 score on a scale Standard Error 0.115	-0.69 score on a scale Standard Error 0.110
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Hour 36	-0.63 score on a scale Standard Error 0.111	-0.82 score on a scale Standard Error 0.121	-0.74 score on a scale Standard Error 0.115
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Hour 48	-0.74 score on a scale Standard Error 0.098	-0.78 score on a scale Standard Error 0.105	-0.78 score on a scale Standard Error 0.102
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Hour 72	-0.65 score on a scale Standard Error 0.112	-0.85 score on a scale Standard Error 0.120	-0.82 score on a scale Standard Error 0.116
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Day 7	-0.60 score on a scale Standard Error 0.098	-0.78 score on a scale Standard Error 0.104	-0.66 score on a scale Standard Error 0.102
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Day 14	-0.87 score on a scale Standard Error 0.114	-0.75 score on a scale Standard Error 0.126	-0.82 score on a scale Standard Error 0.121
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Day 21	-0.61 score on a scale Standard Error 0.142	-0.69 score on a scale Standard Error 0.161	-0.76 score on a scale Standard Error 0.149
Change From Baseline in HAM-D Individual Item Scores Agitation, Change at Day 30	-0.64 score on a scale Standard Error 0.112	-0.80 score on a scale Standard Error 0.122	-0.62 score on a scale Standard Error 0.121
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Hour 2	-0.60 score on a scale Standard Error 0.134	-0.70 score on a scale Standard Error 0.144	-0.76 score on a scale Standard Error 0.140
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Hour 4	-0.90 score on a scale Standard Error 0.158	-1.26 score on a scale Standard Error 0.169	-1.12 score on a scale Standard Error 0.164
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Hour 8	-1.25 score on a scale Standard Error 0.161	-1.41 score on a scale Standard Error 0.172	-1.22 score on a scale Standard Error 0.167
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Hour 12	-1.39 score on a scale Standard Error 0.154	-1.52 score on a scale Standard Error 0.167	-1.35 score on a scale Standard Error 0.161
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Hour 24	-1.16 score on a scale Standard Error 0.148	-1.79 score on a scale Standard Error 0.159	-1.59 score on a scale Standard Error 0.153
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Hour 36	-1.37 score on a scale Standard Error 0.149	-1.99 score on a scale Standard Error 0.162	-1.41 score on a scale Standard Error 0.155
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Hour 48	-1.41 score on a scale Standard Error 0.149	-1.86 score on a scale Standard Error 0.161	-1.71 score on a scale Standard Error 0.156
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Hour 60	-1.48 score on a scale Standard Error 0.141	-1.97 score on a scale Standard Error 0.152	-1.64 score on a scale Standard Error 0.149
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Hour 72	-1.55 score on a scale Standard Error 0.152	-1.84 score on a scale Standard Error 0.164	-1.61 score on a scale Standard Error 0.159
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Day 7	-1.25 score on a scale Standard Error 0.149	-1.44 score on a scale Standard Error 0.160	-1.30 score on a scale Standard Error 0.156
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Day 14	-1.42 score on a scale Standard Error 0.184	-1.45 score on a scale Standard Error 0.204	-1.17 score on a scale Standard Error 0.195
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Day 21	-1.17 score on a scale Standard Error 0.197	-1.26 score on a scale Standard Error 0.221	-1.34 score on a scale Standard Error 0.207
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic, Change at Day 30	-1.15 score on a scale Standard Error 0.161	-1.45 score on a scale Standard Error 0.176	-1.43 score on a scale Standard Error 0.173
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Hour 2	-0.56 score on a scale Standard Error 0.133	-0.67 score on a scale Standard Error 0.142	-0.75 score on a scale Standard Error 0.137
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Hour 4	-0.86 score on a scale Standard Error 0.144	-1.09 score on a scale Standard Error 0.154	-0.88 score on a scale Standard Error 0.149
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Hour 8	-0.79 score on a scale Standard Error 0.135	-1.22 score on a scale Standard Error 0.145	-1.05 score on a scale Standard Error 0.140
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Hour 12	-0.86 score on a scale Standard Error 0.130	-1.16 score on a scale Standard Error 0.141	-0.91 score on a scale Standard Error 0.135
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Hour 24	-0.77 score on a scale Standard Error 0.116	-1.24 score on a scale Standard Error 0.125	-1.12 score on a scale Standard Error 0.120
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Hour 36	-0.86 score on a scale Standard Error 0.127	-1.34 score on a scale Standard Error 0.140	-1.08 score on a scale Standard Error 0.133
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Hour 48	-0.86 score on a scale Standard Error 0.125	-1.42 score on a scale Standard Error 0.136	-1.20 score on a scale Standard Error 0.131
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Hour 60	-1.00 score on a scale Standard Error 0.122	-1.58 score on a scale Standard Error 0.132	-1.31 score on a scale Standard Error 0.128
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Hour 72	-0.91 score on a scale Standard Error 0.131	-1.58 score on a scale Standard Error 0.142	-1.29 score on a scale Standard Error 0.137
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Day 7	-0.91 score on a scale Standard Error 0.134	-1.28 score on a scale Standard Error 0.143	-0.98 score on a scale Standard Error 0.140
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Day 14	-0.70 score on a scale Standard Error 0.153	-1.08 score on a scale Standard Error 0.169	-0.88 score on a scale Standard Error 0.162
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Day 21	-0.94 score on a scale Standard Error 0.155	-1.40 score on a scale Standard Error 0.175	-1.05 score on a scale Standard Error 0.163
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic, Change at Day 30	-0.80 score on a scale Standard Error 0.151	-1.40 score on a scale Standard Error 0.166	-0.99 score on a scale Standard Error 0.163
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Hour 2	-0.28 score on a scale Standard Error 0.110	-0.29 score on a scale Standard Error 0.118	-0.30 score on a scale Standard Error 0.114
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Hour 4	-0.28 score on a scale Standard Error 0.103	-0.55 score on a scale Standard Error 0.111	-0.44 score on a scale Standard Error 0.107
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Hour 8	-0.42 score on a scale Standard Error 0.109	-0.60 score on a scale Standard Error 0.117	-0.57 score on a scale Standard Error 0.113
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Hour 12	-0.51 score on a scale Standard Error 0.111	-0.79 score on a scale Standard Error 0.121	-0.56 score on a scale Standard Error 0.116
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Hour 24	-0.47 score on a scale Standard Error 0.115	-0.88 score on a scale Standard Error 0.123	-0.79 score on a scale Standard Error 0.118
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Hour 36	-0.54 score on a scale Standard Error 0.111	-1.14 score on a scale Standard Error 0.122	-0.78 score on a scale Standard Error 0.116
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Hour 48	-0.61 score on a scale Standard Error 0.110	-1.16 score on a scale Standard Error 0.119	-0.84 score on a scale Standard Error 0.115
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Hour 60	-0.82 score on a scale Standard Error 0.100	-1.24 score on a scale Standard Error 0.109	-0.96 score on a scale Standard Error 0.106
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Hour 72	-0.68 score on a scale Standard Error 0.102	-1.23 score on a scale Standard Error 0.111	-1.01 score on a scale Standard Error 0.107
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Day 7	-0.63 score on a scale Standard Error 0.114	-1.00 score on a scale Standard Error 0.123	-0.66 score on a scale Standard Error 0.119
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Day 14	-0.77 score on a scale Standard Error 0.126	-1.03 score on a scale Standard Error 0.139	-0.89 score on a scale Standard Error 0.134
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Day 21	-0.70 score on a scale Standard Error 0.132	-1.17 score on a scale Standard Error 0.149	-0.91 score on a scale Standard Error 0.139
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms GI, Change at Day 30	-0.82 score on a scale Standard Error 0.112	-1.14 score on a scale Standard Error 0.123	-0.91 score on a scale Standard Error 0.121
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Hour 2	-0.23 score on a scale Standard Error 0.086	-0.28 score on a scale Standard Error 0.092	-0.14 score on a scale Standard Error 0.089
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Hour 4	-0.27 score on a scale Standard Error 0.093	-0.44 score on a scale Standard Error 0.099	-0.33 score on a scale Standard Error 0.096
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Hour 8	-0.27 score on a scale Standard Error 0.093	-0.33 score on a scale Standard Error 0.099	-0.28 score on a scale Standard Error 0.096
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Hour 12	-0.51 score on a scale Standard Error 0.108	-0.50 score on a scale Standard Error 0.117	-0.49 score on a scale Standard Error 0.113
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Hour 24	-0.60 score on a scale Standard Error 0.119	-0.67 score on a scale Standard Error 0.127	-0.55 score on a scale Standard Error 0.122
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Hour 36	-0.64 score on a scale Standard Error 0.111	-0.70 score on a scale Standard Error 0.122	-0.79 score on a scale Standard Error 0.116
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Hour 48	-0.67 score on a scale Standard Error 0.113	-1.05 score on a scale Standard Error 0.122	-0.90 score on a scale Standard Error 0.117
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Hour 60	-0.78 score on a scale Standard Error 0.111	-1.06 score on a scale Standard Error 0.120	-0.95 score on a scale Standard Error 0.117
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Hour 72	-0.81 score on a scale Standard Error 0.113	-1.26 score on a scale Standard Error 0.121	-1.00 score on a scale Standard Error 0.117
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Day 7	-0.62 score on a scale Standard Error 0.121	-0.91 score on a scale Standard Error 0.129	-0.61 score on a scale Standard Error 0.125
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Day 14	-0.64 score on a scale Standard Error 0.138	-0.92 score on a scale Standard Error 0.152	-0.59 score on a scale Standard Error 0.144
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Day 21	-0.55 score on a scale Standard Error 0.138	-1.04 score on a scale Standard Error 0.154	-0.72 score on a scale Standard Error 0.144
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms General, Change at Day 30	-0.66 score on a scale Standard Error 0.129	-1.00 score on a scale Standard Error 0.140	-0.95 score on a scale Standard Error 0.137
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Hour 2	0.00 score on a scale Standard Error 0.055	0.00 score on a scale Standard Error 0.059	-0.16 score on a scale Standard Error 0.057
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Hour 4	0.00 score on a scale Standard Error 0.067	-0.11 score on a scale Standard Error 0.072	-0.13 score on a scale Standard Error 0.069
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Hour 8	-0.07 score on a scale Standard Error 0.087	-0.16 score on a scale Standard Error 0.093	-0.16 score on a scale Standard Error 0.090
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Hour 12	-0.07 score on a scale Standard Error 0.075	-0.08 score on a scale Standard Error 0.082	-0.24 score on a scale Standard Error 0.079
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Hour 24	-0.16 score on a scale Standard Error 0.100	-0.28 score on a scale Standard Error 0.106	-0.28 score on a scale Standard Error 0.102
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Hour 36	-0.23 score on a scale Standard Error 0.102	-0.46 score on a scale Standard Error 0.111	-0.51 score on a scale Standard Error 0.106
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Hour 48	-0.35 score on a scale Standard Error 0.107	-0.46 score on a scale Standard Error 0.115	-0.63 score on a scale Standard Error 0.110
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Hour 60	-0.35 score on a scale Standard Error 0.108	-0.48 score on a scale Standard Error 0.116	-0.67 score on a scale Standard Error 0.112
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Hour 72	-0.32 score on a scale Standard Error 0.107	-0.57 score on a scale Standard Error 0.115	-0.72 score on a scale Standard Error 0.110
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Day 7	-0.51 score on a scale Standard Error 0.113	-0.71 score on a scale Standard Error 0.120	-0.79 score on a scale Standard Error 0.117
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Day 14	-0.49 score on a scale Standard Error 0.131	-0.70 score on a scale Standard Error 0.144	-0.83 score on a scale Standard Error 0.138
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Day 21	-0.68 score on a scale Standard Error 0.141	-0.90 score on a scale Standard Error 0.159	-0.87 score on a scale Standard Error 0.147
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms, Change at Day 30	-0.82 score on a scale Standard Error 0.131	-0.97 score on a scale Standard Error 0.143	-0.95 score on a scale Standard Error 0.140
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Hour 2	-0.23 score on a scale Standard Error 0.105	-0.29 score on a scale Standard Error 0.113	-0.34 score on a scale Standard Error 0.109
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Hour 4	-0.32 score on a scale Standard Error 0.111	-0.39 score on a scale Standard Error 0.119	-0.34 score on a scale Standard Error 0.116
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Hour 8	-0.23 score on a scale Standard Error 0.114	-0.47 score on a scale Standard Error 0.122	-0.41 score on a scale Standard Error 0.118
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Hour 12	-0.32 score on a scale Standard Error 0.109	-0.41 score on a scale Standard Error 0.118	-0.44 score on a scale Standard Error 0.114
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Hour 24	-0.39 score on a scale Standard Error 0.105	-0.55 score on a scale Standard Error 0.112	-0.48 score on a scale Standard Error 0.109
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Hour 36	-0.39 score on a scale Standard Error 0.104	-0.61 score on a scale Standard Error 0.113	-0.49 score on a scale Standard Error 0.109
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Hour 48	-0.49 score on a scale Standard Error 0.105	-0.63 score on a scale Standard Error 0.113	-0.58 score on a scale Standard Error 0.109
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Hour 60	-0.49 score on a scale Standard Error 0.100	-0.60 score on a scale Standard Error 0.108	-0.59 score on a scale Standard Error 0.105
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Hour 72	-0.60 score on a scale Standard Error 0.098	-0.66 score on a scale Standard Error 0.106	-0.55 score on a scale Standard Error 0.103
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Day 7	-0.49 score on a scale Standard Error 0.095	-0.68 score on a scale Standard Error 0.102	-0.58 score on a scale Standard Error 0.100
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Day 14	-0.54 score on a scale Standard Error 0.120	-0.59 score on a scale Standard Error 0.132	-0.51 score on a scale Standard Error 0.127
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Day 21	-0.84 score on a scale Standard Error 0.107	-0.80 score on a scale Standard Error 0.119	-0.57 score on a scale Standard Error 0.114
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Day 21	-0.10 score on a scale Standard Error 0.042	-0.08 score on a scale Standard Error 0.047	-0.09 score on a scale Standard Error 0.044
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis, Change at Day 30	-0.60 score on a scale Standard Error 0.099	-0.66 score on a scale Standard Error 0.109	-0.60 score on a scale Standard Error 0.108
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Hour 2	-0.05 score on a scale Standard Error 0.057	0.03 score on a scale Standard Error 0.061	0.06 score on a scale Standard Error 0.059
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Hour 4	-0.07 score on a scale Standard Error 0.052	-0.04 score on a scale Standard Error 0.055	0.01 score on a scale Standard Error 0.054
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Hour 8	-0.07 score on a scale Standard Error 0.060	-0.02 score on a scale Standard Error 0.064	-0.04 score on a scale Standard Error 0.062
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Hour 12	-0.09 score on a scale Standard Error 0.068	0.03 score on a scale Standard Error 0.074	-0.09 score on a scale Standard Error 0.071
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Hour 24	-0.07 score on a scale Standard Error 0.084	-0.12 score on a scale Standard Error 0.090	-0.24 score on a scale Standard Error 0.086
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Hour 36	-0.14 score on a scale Standard Error 0.076	-0.10 score on a scale Standard Error 0.082	-0.19 score on a scale Standard Error 0.079
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Hour 48	-0.05 score on a scale Standard Error 0.083	-0.12 score on a scale Standard Error 0.089	-0.26 score on a scale Standard Error 0.086
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Hour 60	-0.09 score on a scale Standard Error 0.095	-0.26 score on a scale Standard Error 0.102	-0.35 score on a scale Standard Error 0.098
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Hour 72	-0.14 score on a scale Standard Error 0.090	-0.20 score on a scale Standard Error 0.097	-0.26 score on a scale Standard Error 0.094
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Day 7	-0.30 score on a scale Standard Error 0.129	-0.36 score on a scale Standard Error 0.137	-0.60 score on a scale Standard Error 0.135
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Day 14	-0.43 score on a scale Standard Error 0.150	-0.42 score on a scale Standard Error 0.164	-0.64 score on a scale Standard Error 0.158
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Day 21	-0.49 score on a scale Standard Error 0.160	-0.59 score on a scale Standard Error 0.177	-0.61 score on a scale Standard Error 0.169
Change From Baseline in HAM-D Individual Item Scores Loss of Weight, Change at Day 30	-0.24 score on a scale Standard Error 0.133	-0.55 score on a scale Standard Error 0.144	-0.48 score on a scale Standard Error 0.143
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Hour 2	-0.01 score on a scale Standard Error 0.037	0.02 score on a scale Standard Error 0.040	0.02 score on a scale Standard Error 0.039
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Hour 4	-0.01 score on a scale Standard Error 0.037	-0.01 score on a scale Standard Error 0.040	0.04 score on a scale Standard Error 0.039
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Hour 8	-0.03 score on a scale Standard Error 0.037	-0.04 score on a scale Standard Error 0.040	0.04 score on a scale Standard Error 0.039
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Hour 12	-0.03 score on a scale Standard Error 0.037	-0.06 score on a scale Standard Error 0.041	0.07 score on a scale Standard Error 0.039
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Hour 24	0.04 score on a scale Standard Error 0.038	-0.01 score on a scale Standard Error 0.040	0.04 score on a scale Standard Error 0.039
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Hour 36	-0.03 score on a scale Standard Error 0.037	-0.04 score on a scale Standard Error 0.041	-0.01 score on a scale Standard Error 0.039
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Hour 48	-0.03 score on a scale Standard Error 0.037	0.02 score on a scale Standard Error 0.040	0.02 score on a scale Standard Error 0.039
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Hour 60	-0.06 score on a scale Standard Error 0.037	-0.06 score on a scale Standard Error 0.040	-0.09 score on a scale Standard Error 0.039
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Hour 72	-0.06 score on a scale Standard Error 0.037	-0.01 score on a scale Standard Error 0.040	-0.06 score on a scale Standard Error 0.039
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Day 7	-0.06 score on a scale Standard Error 0.037	-0.06 score on a scale Standard Error 0.040	-0.03 score on a scale Standard Error 0.039
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Day 14	-0.03 score on a scale Standard Error 0.041	-0.07 score on a scale Standard Error 0.045	-0.09 score on a scale Standard Error 0.044
Change From Baseline in HAM-D Individual Item Scores Insight, Change at Day 30	-0.01 score on a scale Standard Error 0.038	-0.06 score on a scale Standard Error 0.041	-0.08 score on a scale Standard Error 0.041
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Hour 2	-0.27 score on a scale Standard Error 0.078	-0.04 score on a scale Standard Error 0.084	-0.19 score on a scale Standard Error 0.082
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Hour 4	-0.29 score on a scale Standard Error 0.097	-0.22 score on a scale Standard Error 0.104	-0.29 score on a scale Standard Error 0.100
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Hour 8	-0.29 score on a scale Standard Error 0.103	-0.17 score on a scale Standard Error 0.110	-0.36 score on a scale Standard Error 0.107
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Hour 12	-0.22 score on a scale Standard Error 0.092	-0.25 score on a scale Standard Error 0.100	-0.26 score on a scale Standard Error 0.097
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Hour 24	-0.47 score on a scale Standard Error 0.138	-1.10 score on a scale Standard Error 0.149	-0.87 score on a scale Standard Error 0.142
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Hour 36	-0.55 score on a scale Standard Error 0.142	-1.16 score on a scale Standard Error 0.155	-0.84 score on a scale Standard Error 0.147
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Hour 48	-0.76 score on a scale Standard Error 0.144	-1.07 score on a scale Standard Error 0.155	-1.27 score on a scale Standard Error 0.149
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Hour 60	-0.85 score on a scale Standard Error 0.140	-1.10 score on a scale Standard Error 0.151	-1.19 score on a scale Standard Error 0.146
Change From Baseline in HAM-D Individual Item Scores Insomnia - Early, Change at Hour 72	-0.57 score on a scale Standard Error 0.142	-0.96 score on a scale Standard Error 0.153	-0.91 score on a scale Standard Error 0.148

SECONDARY outcome

Timeframe: Baseline, Hour 60, Days 7 and 30

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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).
Change From Baseline at Key Time Points in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Hour 60	-19.98 score on a scale Standard Error 1.688	-26.84 score on a scale Standard Error 1.822	-24.19 score on a scale Standard Error 1.797
Change From Baseline at Key Time Points in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Day 7	-19.01 score on a scale Standard Error 1.865	-23.31 score on a scale Standard Error 2.001	-20.32 score on a scale Standard Error 1.982
Change From Baseline at Key Time Points in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Day 30	-19.43 score on a scale Standard Error 1.917	-25.06 score on a scale Standard Error 2.091	-23.02 score on a scale Standard Error 2.080

SECONDARY outcome

Timeframe: Hour 60, Days 7 and 30

The 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. CGI-I response was defined as having a score of 1 (very much improved) or 2 (much improved).

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).
Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response Hour 60	55.8 percentage of participants	83.8 percentage of participants	82.1 percentage of participants
Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response Day 7	46.5 percentage of participants	71.1 percentage of participants	64.1 percentage of participants
Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response Day 30	52.4 percentage of participants	80.0 percentage of participants	72.2 percentage of participants

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).
Change From Baseline in the Generalized Anxiety Disorder 7-Item Scale (GAD-7) Total Score Hour 60	-6.95 score on a scale Standard Error 1.012	-8.08 score on a scale Standard Error 1.095	-7.99 score on a scale Standard Error 1.087
Change From Baseline in the Generalized Anxiety Disorder 7-Item Scale (GAD-7) Total Score Day 7	-6.57 score on a scale Standard Error 0.947	-9.13 score on a scale Standard Error 1.025	-6.32 score on a scale Standard Error 1.034
Change From Baseline in the Generalized Anxiety Disorder 7-Item Scale (GAD-7) Total Score Day 14	-8.60 score on a scale Standard Error 1.081	-9.20 score on a scale Standard Error 1.210	-8.71 score on a scale Standard Error 1.191
Change From Baseline in the Generalized Anxiety Disorder 7-Item Scale (GAD-7) Total Score Day 21	-8.47 score on a scale Standard Error 1.093	-8.53 score on a scale Standard Error 1.224	-9.22 score on a scale Standard Error 1.199
Change From Baseline in the Generalized Anxiety Disorder 7-Item Scale (GAD-7) Total Score Day 30	-7.70 score on a scale Standard Error 1.023	-9.72 score on a scale Standard Error 1.129	-9.15 score on a scale Standard Error 1.135

SECONDARY outcome

Timeframe: Up to approximately 37 days.

Population: The Safety Set included all randomized participants who started the study drug infusion.

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 treatment-emergent AE (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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).
Percentage of Participants With Treatment-Emergent Adverse Events	51.2 percentage of participants	50.0 percentage of participants	53.7 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 37 days.

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

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 Participants Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 Participants 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).
Time to Change in Antidepressant Medication Time to first start/increase in dose	16 days Interval 5.0 to 22.0	12 days Interval 5.0 to 34.0	8 days Interval 4.0 to 29.0
Time to Change in Antidepressant Medication Time to first stop/decrease in dose	—	29 days Interval 29.0 to 29.0	19 days Interval 19.0 to 19.0

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

SAGE-547 60 μg/kg/h

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

SAGE-547 90 μg/kg/h

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=43 participants at risk Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 participants at risk Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 participants at risk 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).
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/43 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	2.6% 1/38 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	0.00% 0/41 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.
Psychiatric disorders Suicidal ideation	0.00% 0/43 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	2.6% 1/38 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	0.00% 0/41 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.

Other adverse events

Other adverse events
Measure	Placebo n=43 participants at risk Participants received infusion rates equivalent to either the 60 μg/kg/h or 90 μg/kg/h group.	SAGE-547 60 μg/kg/h n=38 participants at risk Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).	SAGE-547 90 μg/kg/h n=41 participants at risk 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).
Gastrointestinal disorders Dry mouth	0.00% 0/43 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	10.5% 4/38 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	0.00% 0/41 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.
Gastrointestinal disorders Nausea	7.0% 3/43 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	2.6% 1/38 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	0.00% 0/41 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.
General disorders Infusion site pain	2.3% 1/43 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	2.6% 1/38 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	9.8% 4/41 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.
Nervous system disorders Dizziness	2.3% 1/43 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	15.8% 6/38 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	14.6% 6/41 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.
Nervous system disorders Headache	16.3% 7/43 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	18.4% 7/38 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	14.6% 6/41 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.
Nervous system disorders Loss of consciousness	0.00% 0/43 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	5.3% 2/38 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	2.4% 1/41 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.
Nervous system disorders Somnolence	7.0% 3/43 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	18.4% 7/38 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	4.9% 2/41 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.
Vascular disorders Flushing	0.00% 0/43 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	5.3% 2/38 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.	0.00% 0/41 • Up to approximately 37 days. The Safety Set included all randomized participants who started the study drug infusion.

Additional Information

Medical Monitor

Sage Therapeutics

Phone: 617-299-8380

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI can either be a party and subject to the same restrictions as the institution, or if not a party, the restrictions are described on the face of the contract (i.e., PI is a contractor of the institution; PI is part of a larger group of study personnel; institution has contracted with or otherwise bound all study personnel under confidentiality obligations and requirements to vest intellectual property to the institution).
Publication restrictions are in place

Restriction type: OTHER