Trial Outcomes & Findings for Study to Evaluate SAGE-547 Injection as Adjunctive Therapy for the Treatment of Super-Refractory Status Epilepticus (NCT NCT02052739)

NCT ID: NCT02052739

Last Updated: 2025-09-15

Results Overview

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 (e.g., 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. TEAEs are defined as those that begin on or after initiation of the infusion of SAGE-547.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Up to Day 29

Results posted on

2025-09-15

Participant Flow

Participants took part in the study at 12 sites in United States from 21 March 2014 to 03 May 2015.

A total of 25 participants were enrolled into the study to receive either SAGE-547 standard dose or SAGE-547 high dose,19 participants of whom completed the study.

Participant milestones

Participant milestones
Measure	SAGE-547 Standard Dose Participants received SAGE-547 intravenous (IV) loading infusion of 286.6 micrograms per kilogram per hour (μg/kg/hr) for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Overall Study STARTED	19	6
Overall Study COMPLETED	14	5
Overall Study NOT COMPLETED	5	1

Reasons for withdrawal

Reasons for withdrawal
Measure	SAGE-547 Standard Dose Participants received SAGE-547 intravenous (IV) loading infusion of 286.6 micrograms per kilogram per hour (μg/kg/hr) for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Overall Study Withdrew due to Adverse Event	3	0
Overall Study Participant Died	2	1

Baseline Characteristics

Study to Evaluate SAGE-547 Injection as Adjunctive Therapy for the Treatment of Super-Refractory Status Epilepticus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.	Total n=25 Participants Total of all reporting groups
Age, Continuous	49.3 years STANDARD_DEVIATION 18.98 • n=5 Participants	42.3 years STANDARD_DEVIATION 22.11 • n=7 Participants	47.6 years STANDARD_DEVIATION 19.52 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	5 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	4 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 29

Population: Safety population included all participants who were initiated with an infusion of SAGE-547.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	17 Participants	6 Participants

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Population: Safety population included all participants who were initiated with an infusion of SAGE-547. Number analyzed is the number of participants with data available for analyses at the given time point.

The National Institutes of Health Stroke Scale (NIH-SS) was used to examine the physical and neurological state of the participants. The NIH-SS is a 15-item assessment with measures of level of consciousness, visual gaze and vision loss, facial palsy, motor ability, ataxia, sensory ability, aphasia, dysarthria, and inattention. The total NIHSS score range is from 0 (normal) to 42 (severe impairment), with higher values indicating greater level of neurological impairment.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score Baseline	34.2 score on a scale Standard Deviation 4.69	33.0 score on a scale Standard Deviation 4.86
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Infusion: 0-24 hours	0.7 score on a scale Standard Deviation 2.30	0.3 score on a scale Standard Deviation 1.51
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Infusion: 25-48 hours	0.8 score on a scale Standard Deviation 3.47	-1.5 score on a scale Standard Deviation 6.19
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Infusion: 49-72 hours	-2.2 score on a scale Standard Deviation 6.70	-2.3 score on a scale Standard Deviation 4.63
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Infusion: 73-96 hours	-2.9 score on a scale Standard Deviation 8.08	-5.5 score on a scale Standard Deviation 6.63
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Infusion: 97-120 hours	-5.6 score on a scale Standard Deviation 7.44	-6.7 score on a scale Standard Deviation 7.20
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Acute Follow-up: 121-144 hours	-7.0 score on a scale Standard Deviation 8.75	-10.8 score on a scale Standard Deviation 10.13
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Acute Follow-up: 145-168 hours	-7.5 score on a scale Standard Deviation 9.78	-12.0 score on a scale Standard Deviation 8.76
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Extended Follow-up: Day 8	-9.0 score on a scale Standard Deviation 9.54	-15.4 score on a scale Standard Deviation 11.82
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Extended Follow-up: Day 15	-16.8 score on a scale Standard Deviation 12.10	-16.6 score on a scale Standard Deviation 13.30
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Extended Follow-up: Day 22	-15.1 score on a scale Standard Deviation 14.35	-17.2 score on a scale Standard Deviation 14.55
Change From Baseline (CFB) in National Institutes of Health Stroke Scale (NIH-SS) Total Score CFB at Extended Follow-up: Day 29	-16.7 score on a scale Standard Deviation 15.34	-20.6 score on a scale Standard Deviation 13.09

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Vital signs included weight, heart rate, blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), respiratory rate, temperature, oxygen saturation. CFB in body weight is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Vital Sign Parameter: Body Weight Baseline	78.263 kilograms (kg) Standard Deviation 25.3905	81.667 kilograms (kg) Standard Deviation 20.3141
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Infusion: 0-24 hours	0.253 kilograms (kg) Standard Deviation 3.3321	0.250 kilograms (kg) Standard Deviation 0.3987
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Infusion: 25-48 hours	1.095 kilograms (kg) Standard Deviation 3.9392	1.083 kilograms (kg) Standard Deviation 2.1424
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Infusion: 49-72 hours	1.444 kilograms (kg) Standard Deviation 3.5787	-0.933 kilograms (kg) Standard Deviation 2.9561
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Infusion: 73-96 hours	1.517 kilograms (kg) Standard Deviation 4.5509	-0.033 kilograms (kg) Standard Deviation 4.4275
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Infusion: 97-120 hours	0.688 kilograms (kg) Standard Deviation 4.3148	1.567 kilograms (kg) Standard Deviation 8.8672
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Acute Follow-up: 121-144 hours	-0.631 kilograms (kg) Standard Deviation 6.3734	1.650 kilograms (kg) Standard Deviation 12.6751
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Acute Follow-up: 145-168 hours	-0.930 kilograms (kg) Standard Deviation 7.7080	-5.100 kilograms (kg) Standard Deviation 4.8298
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Extended Follow-up: Day 8	0.436 kilograms (kg) Standard Deviation 9.5258	-1.720 kilograms (kg) Standard Deviation 7.6392
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Extended Follow-up: Day 15	-0.708 kilograms (kg) Standard Deviation 10.1362	-6.100 kilograms (kg) Standard Deviation 4.7589
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Extended Follow-up: Day 22	0.644 kilograms (kg) Standard Deviation 8.9288	-3.420 kilograms (kg) Standard Deviation 12.4474
Change From Baseline in Vital Sign Parameter: Body Weight CFB at Extended Follow-up: Day 29	-6.130 kilograms (kg) Standard Deviation 13.5243	0.108 kilograms (kg) Standard Deviation 19.4907

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24 hours: Loading-predose and at 15,30,45 minutes;1,2,4,8 and 24 hour;25-48: 48 hour;49-72:72 hours;73-96: 96 hour;97-120:120 hours;Acute follow-up at 121-144,145-168 hours; Extended Follow-up at Days 8, 15, 22 and 29

Vital signs included weight, heart rate, blood pressure (SBP and DBP), respiratory rate, temperature, oxygen saturation. CFB in heart rate is reported in this outcome measure.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24 hours:Loading-predose and at 15,30,45 minutes;1,2,4,8 and 24 hour;25-48: 48 hour;49-72: 72 hour;73-96: 96 hour;97-120:120 hour;Acute follow-up at 121-144,145-168 hours;Extended follow-up at Days 8,15,22 and 29

Vital signs included weight, heart rate, blood pressure (SBP and DBP), respiratory rate, temperature, oxygen saturation. CFB in SBP and DBP is reported in this outcome measure.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24 hours:Loading-predose and at 15,30,45 minutes;1,2,4,8 and 24 hour;25-48: 48 hour;49-72:72 hours;73-96: 96 hour;97-120:120 hours;Acute follow-up at 121-144,145-168 hours;Extended follow-up at Days 8, 15, 22 and 29

Vital signs included weight, heart rate, blood pressure (SBP and DBP), respiratory rate, temperature, oxygen saturation. CFB in respiratory rate is reported in this outcome measure.

Outcome measures

PRIMARY outcome

Vital signs included weight, heart rate, blood pressure (SBP and DBP), respiratory rate, temperature, oxygen saturation. CFB in body temperature is reported in this outcome measure.

Outcome measures

PRIMARY outcome

Vital signs included weight, heart rate, blood pressure (SBP and DBP), respiratory rate, temperature, oxygen saturation. Oxygen saturation is a measure of how much hemoglobin is currently bound to oxygen compared to how much hemoglobin remains unbound. CFB in oxygen saturation is reported in this outcome measure.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in alanine aminotransferase levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels Baseline	48.7 international units per liter (IU/L) Standard Deviation 82.92	40.0 international units per liter (IU/L) Standard Deviation 32.47
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Infusion: 0-24 hours	8.2 international units per liter (IU/L) Standard Deviation 23.96	17.0 international units per liter (IU/L) Standard Deviation 42.85
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Infusion: 25-48 hours	11.0 international units per liter (IU/L) Standard Deviation 39.62	39.3 international units per liter (IU/L) Standard Deviation 69.34
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Infusion: 49-72 hours	5.6 international units per liter (IU/L) Standard Deviation 42.77	36.5 international units per liter (IU/L) Standard Deviation 48.02
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Infusion: 73-96 hours	1.9 international units per liter (IU/L) Standard Deviation 50.97	84.0 international units per liter (IU/L) Standard Deviation 124.28
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Infusion: 97-120 hours	4.3 international units per liter (IU/L) Standard Deviation 64.93	233.3 international units per liter (IU/L) Standard Deviation 475.33
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Acute Follow-up: 121-144 hours	4.6 international units per liter (IU/L) Standard Deviation 75.63	109.5 international units per liter (IU/L) Standard Deviation 222.80
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Acute Follow-up: 145-168 hours	5.6 international units per liter (IU/L) Standard Deviation 72.25	48.5 international units per liter (IU/L) Standard Deviation 107.03
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Extended Follow-up: Day 8	4.9 international units per liter (IU/L) Standard Deviation 69.89	0.4 international units per liter (IU/L) Standard Deviation 29.80
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Extended Follow-up: Day 15	-4.5 international units per liter (IU/L) Standard Deviation 85.06	32.2 international units per liter (IU/L) Standard Deviation 47.21
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Extended Follow-up: Day 22	-3.6 international units per liter (IU/L) Standard Deviation 46.91	44.0 international units per liter (IU/L) Standard Deviation 65.01
Change From Baseline in Serum Chemistry Parameter: Alanine Aminotransferase Levels CFB at Extended Follow-up: Day 29	61.2 international units per liter (IU/L) Standard Deviation 309.38	374.0 international units per liter (IU/L) Standard Deviation 404.96

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Extended Follow-up: Day 8	1.2 grams per liter (g/L) Standard Deviation 4.34	9.2 grams per liter (g/L) Standard Deviation 9.44
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Extended Follow-up: Day 15	2.8 grams per liter (g/L) Standard Deviation 6.45	10.2 grams per liter (g/L) Standard Deviation 6.22
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Extended Follow-up: Day 22	5.7 grams per liter (g/L) Standard Deviation 7.46	9.5 grams per liter (g/L) Standard Deviation 1.73
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Extended Follow-up: Day 29	4.8 grams per liter (g/L) Standard Deviation 7.91	12.3 grams per liter (g/L) Standard Deviation 4.04
Change From Baseline in Serum Chemistry Parameter: Albumin Levels Baseline	26.7 grams per liter (g/L) Standard Deviation 4.87	21.3 grams per liter (g/L) Standard Deviation 3.67
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Infusion: 0-24 hours	-0.3 grams per liter (g/L) Standard Deviation 1.75	-1.3 grams per liter (g/L) Standard Deviation 3.33
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Infusion: 25-48 hours	-0.5 grams per liter (g/L) Standard Deviation 1.84	-0.7 grams per liter (g/L) Standard Deviation 7.17
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Infusion: 49-72 hours	-0.2 grams per liter (g/L) Standard Deviation 2.32	0.7 grams per liter (g/L) Standard Deviation 5.28
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Infusion: 73-96 hours	0.1 grams per liter (g/L) Standard Deviation 2.26	3.8 grams per liter (g/L) Standard Deviation 8.54
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Infusion: 97-120 hours	-0.1 grams per liter (g/L) Standard Deviation 2.45	5.0 grams per liter (g/L) Standard Deviation 6.60
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Acute Follow-up: 121-144 hours	0.3 grams per liter (g/L) Standard Deviation 2.82	5.3 grams per liter (g/L) Standard Deviation 8.71
Change From Baseline in Serum Chemistry Parameter: Albumin Levels CFB at Acute Follow-up: 145-168 hours	0.6 grams per liter (g/L) Standard Deviation 3.61	7.5 grams per liter (g/L) Standard Deviation 8.96

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in aspartate aminotransferase levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels Baseline	43.8 IU/L Standard Deviation 50.41	44.8 IU/L Standard Deviation 35.87
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Infusion: 0-24 hours	0.9 IU/L Standard Deviation 43.24	18.3 IU/L Standard Deviation 31.42
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Infusion: 25-48 hours	7.5 IU/L Standard Deviation 43.28	32.7 IU/L Standard Deviation 30.66
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Infusion: 49-72 hours	-0.8 IU/L Standard Deviation 40.40	24.5 IU/L Standard Deviation 24.99
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Infusion: 73-96 hours	2.4 IU/L Standard Deviation 39.23	146.7 IU/L Standard Deviation 328.43
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Infusion: 97-120 hours	8.7 IU/L Standard Deviation 39.62	854.5 IU/L Standard Deviation 2056.68
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Acute Follow-up: 121-144 hours	11.8 IU/L Standard Deviation 35.16	440.3 IU/L Standard Deviation 1067.48
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Acute Follow-up: 145-168 hours	12.6 IU/L Standard Deviation 29.27	264.7 IU/L Standard Deviation 654.96
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Extended Follow-up: Day 8	10.8 IU/L Standard Deviation 34.72	-5.2 IU/L Standard Deviation 16.63
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Extended Follow-up: Day 15	2.9 IU/L Standard Deviation 33.33	29.0 IU/L Standard Deviation 48.93
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Extended Follow-up: Day 22	15.8 IU/L Standard Deviation 68.73	25.0 IU/L Standard Deviation 55.47
Change From Baseline in Serum Chemistry Parameter: Aspartate Aminotransferase Levels CFB at Extended Follow-up: Day 29	24.9 IU/L Standard Deviation 121.92	1888.0 IU/L Standard Deviation 3115.96

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in bicarbonate levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels Baseline	22.29 millimoles per liter (mmol/L) Standard Deviation 5.247	24.52 millimoles per liter (mmol/L) Standard Deviation 4.481
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Infusion: 0-24 hours	0.29 millimoles per liter (mmol/L) Standard Deviation 2.077	-0.85 millimoles per liter (mmol/L) Standard Deviation 2.411
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Infusion: 25-48 hours	0.68 millimoles per liter (mmol/L) Standard Deviation 3.607	-0.90 millimoles per liter (mmol/L) Standard Deviation 2.205
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Infusion: 49-72 hours	1.12 millimoles per liter (mmol/L) Standard Deviation 3.252	-0.98 millimoles per liter (mmol/L) Standard Deviation 3.060
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Infusion: 73-96 hours	1.10 millimoles per liter (mmol/L) Standard Deviation 3.258	-0.20 millimoles per liter (mmol/L) Standard Deviation 3.200
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Infusion: 97-120 hours	1.42 millimoles per liter (mmol/L) Standard Deviation 4.187	-0.83 millimoles per liter (mmol/L) Standard Deviation 4.262
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Acute Follow-up: 121-144 hours	1.68 millimoles per liter (mmol/L) Standard Deviation 4.834	-1.75 millimoles per liter (mmol/L) Standard Deviation 5.511
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Acute Follow-up: 145-168 hours	1.85 millimoles per liter (mmol/L) Standard Deviation 5.119	-2.15 millimoles per liter (mmol/L) Standard Deviation 5.829
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Extended Follow-up: Day 8	1.27 millimoles per liter (mmol/L) Standard Deviation 5.397	-0.06 millimoles per liter (mmol/L) Standard Deviation 4.463
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Extended Follow-up: Day 15	0.95 millimoles per liter (mmol/L) Standard Deviation 5.309	1.14 millimoles per liter (mmol/L) Standard Deviation 6.527
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Extended Follow-up: Day 22	1.45 millimoles per liter (mmol/L) Standard Deviation 6.239	1.56 millimoles per liter (mmol/L) Standard Deviation 5.447
Change From Baseline in Serum Chemistry Parameter: Bicarbonate Levels CFB at Extended Follow-up: Day 29	2.59 millimoles per liter (mmol/L) Standard Deviation 6.432	0.25 millimoles per liter (mmol/L) Standard Deviation 6.850

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in bilirubin levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels Baseline	15.3900 micromoles per liter (μmol/L) Standard Deviation 37.32086	6.8400 micromoles per liter (μmol/L) Standard Deviation 7.41438
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Infusion: 0-24 hours	-2.8165 micromoles per liter (μmol/L) Standard Deviation 7.32863	0.8550 micromoles per liter (μmol/L) Standard Deviation 2.35707
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Infusion: 25-48 hours	-3.0176 micromoles per liter (μmol/L) Standard Deviation 8.68845	0.0000 micromoles per liter (μmol/L) Standard Deviation 5.72275
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Infusion: 49-72 hours	-1.0688 micromoles per liter (μmol/L) Standard Deviation 3.11420	-1.4250 micromoles per liter (μmol/L) Standard Deviation 6.15758
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Infusion: 73-96 hours	1.9237 micromoles per liter (μmol/L) Standard Deviation 5.14423	-0.8550 micromoles per liter (μmol/L) Standard Deviation 5.59356
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Infusion: 97-120 hours	1.3680 micromoles per liter (μmol/L) Standard Deviation 6.27296	0.0000 micromoles per liter (μmol/L) Standard Deviation 7.33508
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Acute Follow-up: 121-144 hours	1.4657 micromoles per liter (μmol/L) Standard Deviation 6.56677	0.5700 micromoles per liter (μmol/L) Standard Deviation 9.34522
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Acute Follow-up: 145-168 hours	3.9086 micromoles per liter (μmol/L) Standard Deviation 10.20347	3.7050 micromoles per liter (μmol/L) Standard Deviation 14.56682
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Extended Follow-up: Day 8	7.2064 micromoles per liter (μmol/L) Standard Deviation 18.06184	-2.0520 micromoles per liter (μmol/L) Standard Deviation 7.49284
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Extended Follow-up: Day 15	7.6292 micromoles per liter (μmol/L) Standard Deviation 25.00165	-2.3940 micromoles per liter (μmol/L) Standard Deviation 7.31512
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Extended Follow-up: Day 22	4.4197 micromoles per liter (μmol/L) Standard Deviation 18.18369	-0.4275 micromoles per liter (μmol/L) Standard Deviation 5.10619
Change From Baseline in Serum Chemistry Parameter: Bilirubin Levels CFB at Extended Follow-up: Day 29	26.5050 micromoles per liter (μmol/L) Standard Deviation 69.14760	2.2800 micromoles per liter (μmol/L) Standard Deviation 1.97454

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in blood urea nitrogen levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Extended Follow-up: Day 8	1.8743 mmol/L Standard Deviation 2.74527	1.1424 mmol/L Standard Deviation 2.55448
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels Baseline	4.7162 mmol/L Standard Deviation 2.04935	4.9980 mmol/L Standard Deviation 1.62817
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Infusion: 0-24 hours	0.5752 mmol/L Standard Deviation 0.90926	-0.1785 mmol/L Standard Deviation 0.58661
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Infusion: 25-48 hours	1.2025 mmol/L Standard Deviation 1.55708	-0.7140 mmol/L Standard Deviation 1.17322
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Infusion: 49-72 hours	1.3090 mmol/L Standard Deviation 1.79547	-0.8925 mmol/L Standard Deviation 1.16778
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Infusion: 73-96 hours	1.6462 mmol/L Standard Deviation 2.02001	-0.1785 mmol/L Standard Deviation 1.99090
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Infusion: 97-120 hours	2.0160 mmol/L Standard Deviation 2.22925	0.6545 mmol/L Standard Deviation 2.82384
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Acute Follow-up: 121-144 hours	2.1000 mmol/L Standard Deviation 2.37104	2.0825 mmol/L Standard Deviation 2.79663
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Acute Follow-up: 145-168 hours	2.1197 mmol/L Standard Deviation 2.64106	1.9040 mmol/L Standard Deviation 2.79890
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Extended Follow-up: Day 15	1.5396 mmol/L Standard Deviation 2.64507	0.0714 mmol/L Standard Deviation 2.14794
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Extended Follow-up: Day 22	2.0145 mmol/L Standard Deviation 5.10015	-0.0714 mmol/L Standard Deviation 3.73914
Change From Baseline in Serum Chemistry Parameter: Blood Urea Nitrogen Levels CFB at Extended Follow-up: Day 29	1.0115 mmol/L Standard Deviation 3.40329	1.3388 mmol/L Standard Deviation 0.79160

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in calcium levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Calcium Levels Baseline	0.2037 mmol/L Standard Deviation 0.01153	0.1950 mmol/L Standard Deviation 0.02074
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Infusion: 0-24 hours	0.0015 mmol/L Standard Deviation 0.00733	0.0021 mmol/L Standard Deviation 0.00732
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Infusion: 25-48 hours	0.0036 mmol/L Standard Deviation 0.00984	0.0017 mmol/L Standard Deviation 0.01765
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Infusion: 49-72 hours	0.0056 mmol/L Standard Deviation 0.01521	0.0067 mmol/L Standard Deviation 0.02149
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Infusion: 73-96 hours	0.0078 mmol/L Standard Deviation 0.01522	0.0079 mmol/L Standard Deviation 0.02947
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Infusion: 97-120 hours	0.0084 mmol/L Standard Deviation 0.01714	0.0117 mmol/L Standard Deviation 0.02493
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Acute Follow-up: 121-144 hours	0.0071 mmol/L Standard Deviation 0.01703	0.0125 mmol/L Standard Deviation 0.02766
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Acute Follow-up: 145-168 hours	0.0100 mmol/L Standard Deviation 0.01180	0.0092 mmol/L Standard Deviation 0.02553
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Extended Follow-up: Day 8	0.0114 mmol/L Standard Deviation 0.01016	0.0170 mmol/L Standard Deviation 0.01866
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Extended Follow-up: Day 15	0.0172 mmol/L Standard Deviation 0.01873	0.0170 mmol/L Standard Deviation 0.01681
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Extended Follow-up: Day 22	0.0202 mmol/L Standard Deviation 0.03017	0.0219 mmol/L Standard Deviation 0.00688
Change From Baseline in Serum Chemistry Parameter: Calcium Levels CFB at Extended Follow-up: Day 29	0.0121 mmol/L Standard Deviation 0.02749	0.0300 mmol/L Standard Deviation 0.00750

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in chloride levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Chloride Levels Baseline	110.0 mmol/L Standard Deviation 6.21	109.7 mmol/L Standard Deviation 3.72
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Infusion: 0-24 hours	0.2 mmol/L Standard Deviation 2.82	-3.5 mmol/L Standard Deviation 3.56
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Infusion: 25-48 hours	-0.6 mmol/L Standard Deviation 3.32	-0.5 mmol/L Standard Deviation 5.17
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Infusion: 49-72 hours	-1.1 mmol/L Standard Deviation 3.74	0.5 mmol/L Standard Deviation 6.60
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Infusion: 73-96 hours	-1.6 mmol/L Standard Deviation 4.22	-0.3 mmol/L Standard Deviation 4.63
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Infusion: 97-120 hours	-2.9 mmol/L Standard Deviation 5.07	-2.7 mmol/L Standard Deviation 2.73
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Acute Follow-up: 121-144 hours	-2.5 mmol/L Standard Deviation 6.96	-1.8 mmol/L Standard Deviation 4.92
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Acute Follow-up: 145-168 hours	-4.1 mmol/L Standard Deviation 7.36	-1.2 mmol/L Standard Deviation 3.97
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Extended Follow-up: Day 8	-4.0 mmol/L Standard Deviation 7.32	-3.4 mmol/L Standard Deviation 5.55
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Extended Follow-up: Day 15	-5.9 mmol/L Standard Deviation 9.02	-4.6 mmol/L Standard Deviation 12.12
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Extended Follow-up: Day 22	-4.1 mmol/L Standard Deviation 8.63	-10.8 mmol/L Standard Deviation 5.81
Change From Baseline in Serum Chemistry Parameter: Chloride Levels CFB at Extended Follow-up: Day 29	-7.2 mmol/L Standard Deviation 6.73	-11.0 mmol/L Standard Deviation 4.69

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in creatine kinase levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels Baseline	164.6 IU/L Standard Deviation 297.58	1056.4 IU/L Standard Deviation 1476.88
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Infusion: 0-24 hours	-5.4 IU/L Standard Deviation 99.29	80.0 IU/L Standard Deviation 343.91
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Infusion: 25-48 hours	-41.5 IU/L Standard Deviation 204.71	-77.0 IU/L Standard Deviation 226.45
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Infusion: 49-72 hours	-52.8 IU/L Standard Deviation 240.39	-35.2 IU/L Standard Deviation 375.74
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Infusion: 73-96 hours	-54.8 IU/L Standard Deviation 250.36	187.8 IU/L Standard Deviation 428.72
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Infusion: 97-120 hours	-69.4 IU/L Standard Deviation 267.62	1034.6 IU/L Standard Deviation 2557.56
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Acute Follow-up: 121-144 hours	-94.9 IU/L Standard Deviation 280.01	864.2 IU/L Standard Deviation 2487.87
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Acute Follow-up: 145-168 hours	-43.8 IU/L Standard Deviation 269.89	1462.6 IU/L Standard Deviation 3745.02
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Extended Follow-up: Day 8	-39.5 IU/L Standard Deviation 286.63	-67.0 IU/L Standard Deviation 684.14
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Extended Follow-up: Day 15	-70.5 IU/L Standard Deviation 293.08	-294.5 IU/L Standard Deviation 520.14
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Extended Follow-up: Day 22	-108.7 IU/L Standard Deviation 284.99	-245.5 IU/L Standard Deviation 217.08
Change From Baseline in Serum Chemistry Parameter: Creatine Kinase Levels CFB at Extended Follow-up: Day 29	5.9 IU/L Standard Deviation 51.57	-356.7 IU/L Standard Deviation 596.58

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in creatinine levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels Baseline	61.8335 μmol/L Standard Deviation 38.35138	66.1527 μmol/L Standard Deviation 26.85624
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Infusion: 0-24 hours	3.5851 μmol/L Standard Deviation 21.18016	-4.2727 μmol/L Standard Deviation 3.96981
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Infusion: 25-48 hours	-0.3257 μmol/L Standard Deviation 17.04796	-2.7993 μmol/L Standard Deviation 9.97654
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Infusion: 49-72 hours	-5.4513 μmol/L Standard Deviation 17.92081	-5.1567 μmol/L Standard Deviation 13.15250
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Infusion: 73-96 hours	-9.0364 μmol/L Standard Deviation 24.69353	2.6520 μmol/L Standard Deviation 34.21891
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Infusion: 97-120 hours	-11.1800 μmol/L Standard Deviation 28.19797	15.1753 μmol/L Standard Deviation 34.57069
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Acute Follow-up: 121-144 hours	-10.4000 μmol/L Standard Deviation 30.51166	32.4133 μmol/L Standard Deviation 73.92834
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Acute Follow-up: 145-168 hours	-6.5748 μmol/L Standard Deviation 39.93224	37.8647 μmol/L Standard Deviation 103.07822
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Extended Follow-up: Day 8	-9.8345 μmol/L Standard Deviation 34.60628	-1.5912 μmol/L Standard Deviation 12.81648
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Extended Follow-up: Day 15	-7.1825 μmol/L Standard Deviation 30.96420	-3.3592 μmol/L Standard Deviation 13.75749
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Extended Follow-up: Day 22	-4.6726 μmol/L Standard Deviation 33.58740	-11.6688 μmol/L Standard Deviation 33.48365
Change From Baseline in Serum Chemistry Parameter: Creatinine Levels CFB at Extended Follow-up: Day 29	11.7867 μmol/L Standard Deviation 78.66321	0.0000 μmol/L Standard Deviation 23.06320

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in glucose levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Glucose Levels Baseline	7.0731 mmol/L Standard Deviation 1.60940	7.1238 mmol/L Standard Deviation 2.48860
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Infusion: 0-24 hours	0.7247 mmol/L Standard Deviation 1.21847	2.5905 mmol/L Standard Deviation 3.70841
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Infusion: 25-48 hours	0.2542 mmol/L Standard Deviation 1.75414	0.6661 mmol/L Standard Deviation 1.44582
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Infusion: 49-72 hours	1.0886 mmol/L Standard Deviation 2.99912	1.4155 mmol/L Standard Deviation 3.15690
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Infusion: 73-96 hours	0.0956 mmol/L Standard Deviation 1.98021	0.2405 mmol/L Standard Deviation 1.85063
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Infusion: 97-120 hours	0.4539 mmol/L Standard Deviation 1.53147	0.2035 mmol/L Standard Deviation 2.89966
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Acute Follow-up: 121-144 hours	0.1437 mmol/L Standard Deviation 2.20744	0.5644 mmol/L Standard Deviation 1.44173
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Acute Follow-up: 145-168 hours	-0.1457 mmol/L Standard Deviation 1.83254	-0.2683 mmol/L Standard Deviation 1.26456
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Extended Follow-up: Day 8	-0.1596 mmol/L Standard Deviation 1.85981	-1.4766 mmol/L Standard Deviation 2.48794
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Extended Follow-up: Day 15	-0.4788 mmol/L Standard Deviation 1.91895	-0.0999 mmol/L Standard Deviation 3.18721
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Extended Follow-up: Day 22	-0.4084 mmol/L Standard Deviation 2.50478	-0.1554 mmol/L Standard Deviation 4.07581
Change From Baseline in Serum Chemistry Parameter: Glucose Levels CFB at Extended Follow-up: Day 29	-1.1565 mmol/L Standard Deviation 1.79106	-1.5959 mmol/L Standard Deviation 2.23900

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Lipase Levels Baseline	69.7 IU/L Standard Deviation 108.56	48.3 IU/L Standard Deviation 55.19
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Infusion: 0-24 hours	-13.4 IU/L Standard Deviation 43.77	3.3 IU/L Standard Deviation 3.21
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Infusion: 25-48 hours	-7.5 IU/L Standard Deviation 34.95	9.3 IU/L Standard Deviation 13.58
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Infusion: 49-72 hours	-14.4 IU/L Standard Deviation 36.77	0.0 IU/L Standard Deviation 1.73
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Infusion: 73-96 hours	-22.4 IU/L Standard Deviation 64.01	18.0 IU/L Standard Deviation 25.36
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Infusion: 97-120 hours	-20.5 IU/L Standard Deviation 63.33	-6.7 IU/L Standard Deviation 22.74
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Acute Follow-up: 121-144 hours	-20.3 IU/L Standard Deviation 91.54	-10.7 IU/L Standard Deviation 37.87
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Acute Follow-up: 145-168 hours	-11.7 IU/L Standard Deviation 99.60	9.3 IU/L Standard Deviation 16.92
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Extended Follow-up: Day 8	-3.7 IU/L Standard Deviation 100.78	37.0 IU/L Standard Deviation 28.16
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Extended Follow-up: Day 15	24.7 IU/L Standard Deviation 44.42	19.7 IU/L Standard Deviation 100.17
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Extended Follow-up: Day 22	14.1 IU/L Standard Deviation 38.25	-15.0 IU/L Standard Deviation 84.85
Change From Baseline in Serum Chemistry Parameter: Lipase Levels CFB at Extended Follow-up: Day 29	-8.3 IU/L Standard Deviation 35.42	0.0 IU/L Standard Deviation 31.00

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in magnesium levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels Baseline	0.8969 mmol/L Standard Deviation 0.19546	0.8607 mmol/L Standard Deviation 0.14418
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Infusion: 0-24 hours	-0.0219 mmol/L Standard Deviation 0.11853	-0.0441 mmol/L Standard Deviation 0.06638
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Infusion: 25-48 hours	-0.0194 mmol/L Standard Deviation 0.14406	-0.0319 mmol/L Standard Deviation 0.11737
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Infusion: 49-72 hours	-0.0430 mmol/L Standard Deviation 0.11666	-0.0167 mmol/L Standard Deviation 0.12869
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Infusion: 73-96 hours	-0.0374 mmol/L Standard Deviation 0.17268	0.0304 mmol/L Standard Deviation 0.16521
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Infusion: 97-120 hours	-0.0151 mmol/L Standard Deviation 0.22358	0.0754 mmol/L Standard Deviation 0.10859
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Acute Follow-up: 121-144 hours	-0.0348 mmol/L Standard Deviation 0.18742	0.0534 mmol/L Standard Deviation 0.13315
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Acute Follow-up: 145-168 hours	-0.0151 mmol/L Standard Deviation 0.21498	0.0519 mmol/L Standard Deviation 0.15865
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Extended Follow-up: Day 8	-0.0435 mmol/L Standard Deviation 0.15736	-0.0811 mmol/L Standard Deviation 0.16860
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Extended Follow-up: Day 15	-0.0645 mmol/L Standard Deviation 0.15320	-0.0494 mmol/L Standard Deviation 0.09381
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Extended Follow-up: Day 22	-0.0564 mmol/L Standard Deviation 0.19263	-0.1264 mmol/L Standard Deviation 0.15097
Change From Baseline in Serum Chemistry Parameter: Magnesium Levels CFB at Extended Follow-up: Day 29	-0.1484 mmol/L Standard Deviation 0.28794	-0.0608 mmol/L Standard Deviation 0.08902

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in potassium levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Potassium Levels Baseline	3.76 mmol/L Standard Deviation 0.439	3.87 mmol/L Standard Deviation 0.301
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Infusion: 0-24 hours	0.01 mmol/L Standard Deviation 0.515	-0.03 mmol/L Standard Deviation 0.242
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Infusion: 25-48 hours	0.15 mmol/L Standard Deviation 0.717	-0.10 mmol/L Standard Deviation 0.329
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Infusion: 49-72 hours	0.17 mmol/L Standard Deviation 0.788	-0.37 mmol/L Standard Deviation 1.117
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Infusion: 73-96 hours	0.05 mmol/L Standard Deviation 0.651	0.22 mmol/L Standard Deviation 0.601
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Infusion: 97-120 hours	0.00 mmol/L Standard Deviation 0.446	0.35 mmol/L Standard Deviation 0.497
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Acute Follow-up: 121-144 hours	-0.02 mmol/L Standard Deviation 0.542	0.37 mmol/L Standard Deviation 0.582
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Acute Follow-up: 145-168 hours	-0.06 mmol/L Standard Deviation 0.578	0.75 mmol/L Standard Deviation 0.946
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Extended Follow-up: Day 8	0.07 mmol/L Standard Deviation 0.585	0.10 mmol/L Standard Deviation 0.255
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Extended Follow-up: Day 15	0.04 mmol/L Standard Deviation 0.734	0.42 mmol/L Standard Deviation 0.657
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Extended Follow-up: Day 22	0.12 mmol/L Standard Deviation 0.654	0.32 mmol/L Standard Deviation 0.683
Change From Baseline in Serum Chemistry Parameter: Potassium Levels CFB at Extended Follow-up: Day 29	0.21 mmol/L Standard Deviation 0.442	0.38 mmol/L Standard Deviation 0.741

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Serum chemistry measures included alanine aminotransferase, albumin, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, calcium, chloride, creatine kinase, creatinine, glucose, lipase, magnesium, potassium, protein, sodium. CFB in protein levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Protein Levels Baseline	56.5 g/L Standard Deviation 9.91	52.2 g/L Standard Deviation 7.52
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Infusion: 0-24 hours	0.4 g/L Standard Deviation 1.71	1.0 g/L Standard Deviation 5.51
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Infusion: 25-48 hours	1.1 g/L Standard Deviation 2.34	1.5 g/L Standard Deviation 5.92
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Infusion: 49-72 hours	1.3 g/L Standard Deviation 4.08	4.0 g/L Standard Deviation 6.69
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Infusion: 73-96 hours	2.5 g/L Standard Deviation 4.10	6.5 g/L Standard Deviation 5.99
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Infusion: 97-120 hours	2.8 g/L Standard Deviation 2.96	8.8 g/L Standard Deviation 7.41
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Acute Follow-up: 121-144 hours	2.5 g/L Standard Deviation 5.05	6.3 g/L Standard Deviation 5.89
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Acute Follow-up: 145-168 hours	4.1 g/L Standard Deviation 4.87	7.5 g/L Standard Deviation 5.05
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Extended Follow-up: Day 8	4.3 g/L Standard Deviation 5.06	5.6 g/L Standard Deviation 5.68
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Extended Follow-up: Day 15	5.9 g/L Standard Deviation 9.21	11.0 g/L Standard Deviation 6.44
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Extended Follow-up: Day 22	6.7 g/L Standard Deviation 10.18	16.5 g/L Standard Deviation 8.19
Change From Baseline in Serum Chemistry Parameter: Protein Levels CFB at Extended Follow-up: Day 29	7.1 g/L Standard Deviation 11.56	20.0 g/L Standard Deviation 7.21

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Serum Chemistry Parameter: Sodium Levels Baseline	140.6 mmol/L Standard Deviation 4.84	141.7 mmol/L Standard Deviation 4.84
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Infusion: 0-24 hours	0.1 mmol/L Standard Deviation 2.87	-3.8 mmol/L Standard Deviation 4.12
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Infusion: 25-48 hours	0.7 mmol/L Standard Deviation 4.31	0.3 mmol/L Standard Deviation 5.72
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Infusion: 49-72 hours	0.4 mmol/L Standard Deviation 3.88	1.7 mmol/L Standard Deviation 6.19
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Infusion: 73-96 hours	0.4 mmol/L Standard Deviation 3.50	1.5 mmol/L Standard Deviation 3.94
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Infusion: 97-120 hours	0.0 mmol/L Standard Deviation 4.80	-0.5 mmol/L Standard Deviation 4.04
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Acute Follow-up: 121-144 hours	-0.3 mmol/L Standard Deviation 5.12	-1.0 mmol/L Standard Deviation 4.60
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Acute Follow-up: 145-168 hours	-1.2 mmol/L Standard Deviation 5.64	0.2 mmol/L Standard Deviation 5.85
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Extended Follow-up: Day 8	-1.8 mmol/L Standard Deviation 5.65	0.0 mmol/L Standard Deviation 5.79
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Extended Follow-up: Day 15	-2.8 mmol/L Standard Deviation 5.51	-0.4 mmol/L Standard Deviation 7.64
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Extended Follow-up: Day 22	0.0 mmol/L Standard Deviation 5.53	-3.2 mmol/L Standard Deviation 4.32
Change From Baseline in Serum Chemistry Parameter: Sodium Levels CFB at Extended Follow-up: Day 29	-1.8 mmol/L Standard Deviation 6.34	-4.5 mmol/L Standard Deviation 1.29

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in basophil levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Basophil Levels Baseline	0.031 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0509	0.037 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0321
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Infusion: 0-24 hours	0.013 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0308	0.003 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0058
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Infusion: 25-48 hours	-0.008 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0319	-0.023 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0321
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Infusion: 49-72 hours	0.009 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0230	-0.007 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0208
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Infusion: 73-96 hours	0.013 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0433	-0.013 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0115
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Infusion: 97-120 hours	0.004 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0662	-0.010 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0141
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Acute Follow-up: 121-144 hours	0.033 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0369	0.087 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.1848
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Acute Follow-up: 145-168 hours	0.006 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0669	-0.017 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0153
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Extended Follow-up: Day 8	0.014 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0745	-0.017 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0153
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Extended Follow-up: Day 15	0.031 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0366	0.040 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0849
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Extended Follow-up: Day 22	0.020 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0216	0.000 10^3 cells per microliter(10^3 cells/uL)
Change From Baseline in Hematology Parameter: Basophil Levels CFB at Extended Follow-up: Day 29	0.017 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0288	-0.005 10^3 cells per microliter(10^3 cells/uL) Standard Deviation 0.0071

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Population: Safety Population included all participants who were initiated with an infusion of SAGE-547. Number analyzed is the number of participants with data available for analyses at the given time point.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells Baseline	0.50 percentage of cells Standard Deviation 0.707	0.00 percentage of cells Standard Deviation 0.000
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 0-24 hours	0.00 percentage of cells	0.00 percentage of cells
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 25-48 hours	0.00 percentage of cells Standard Deviation 0.000	1.00 percentage of cells
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 49-72 hours	0.00 percentage of cells Standard Deviation 0.000	0.00 percentage of cells
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 73-96 hours	0.50 percentage of cells Standard Deviation 0.707	1.00 percentage of cells
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 97-120 hours	0.00 percentage of cells Standard Deviation 0.000	1.00 percentage of cells
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Acute Follow-up: 121-144 hours	0.00 percentage of cells Standard Deviation 0.000	0.00 percentage of cells
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Acute Follow-up: 145-168 hours	0.00 percentage of cells Standard Deviation 0.000	0.00 percentage of cells
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 8	0.00 percentage of cells Standard Deviation 0.000	—
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 15	-0.50 percentage of cells Standard Deviation 0.707	—
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 22	0.50 percentage of cells Standard Deviation 0.707	0.00 percentage of cells
Change From Baseline in Hematology Parameter: Basophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 29	0.00 percentage of cells Standard Deviation 0.000	—

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in eosinophils levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Eosinophil Levels Baseline	0.3364 10^3 cells/uL Standard Deviation 0.42711	0.7433 10^3 cells/uL Standard Deviation 0.20108
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Infusion: 0-24 hours	0.0580 10^3 cells/uL Standard Deviation 0.17813	-0.2700 10^3 cells/uL Standard Deviation 0.24269
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Infusion: 25-48 hours	0.0660 10^3 cells/uL Standard Deviation 0.23538	-0.2333 10^3 cells/uL Standard Deviation 0.45654
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Infusion: 49-72 hours	-0.0911 10^3 cells/uL Standard Deviation 0.35069	-0.6467 10^3 cells/uL Standard Deviation 0.14189
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Infusion: 73-96 hours	-0.0811 10^3 cells/uL Standard Deviation 0.36381	-0.5867 10^3 cells/uL Standard Deviation 0.07095
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Infusion: 97-120 hours	-0.1878 10^3 cells/uL Standard Deviation 0.45535	-0.4200 10^3 cells/uL Standard Deviation 0.41940
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Acute Follow-up: 121-144 hours	-0.2211 10^3 cells/uL Standard Deviation 0.44552	-0.5567 10^3 cells/uL Standard Deviation 0.16258
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Acute Follow-up: 145-168 hours	-0.1643 10^3 cells/uL Standard Deviation 0.42177	-0.5567 10^3 cells/uL Standard Deviation 0.17898
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Extended Follow-up: Day 8	-0.1056 10^3 cells/uL Standard Deviation 0.40423	-0.5400 10^3 cells/uL Standard Deviation 0.17776
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Extended Follow-up: Day 15	-0.0078 10^3 cells/uL Standard Deviation 0.33774	0.0100 10^3 cells/uL Standard Deviation 0.26870
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Extended Follow-up: Day 22	-0.0543 10^3 cells/uL Standard Deviation 0.42496	-0.3000 10^3 cells/uL
Change From Baseline in Hematology Parameter: Eosinophil Levels CFB at Extended Follow-up: Day 29	-0.0229 10^3 cells/uL Standard Deviation 0.39982	-0.5650 10^3 cells/uL Standard Deviation 0.33234

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in eosinophils to leukocytes ratio is reported in terms of percentage of cells in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells Baseline	3.00 percentage of cells Standard Deviation 0.000	3.00 percentage of cells Standard Deviation 0.000
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 0-24 hours	5.00 percentage of cells	-2.00 percentage of cells
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 25-48 hours	0.50 percentage of cells Standard Deviation 0.707	0.00 percentage of cells
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 49-72 hours	-0.50 percentage of cells Standard Deviation 2.121	0.00 percentage of cells
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 73-96 hours	0.50 percentage of cells Standard Deviation 0.707	-2.00 percentage of cells
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 97-120 hours	-1.00 percentage of cells Standard Deviation 0.000	-2.00 percentage of cells
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Acute Follow-up: 121-144 hours	-1.50 percentage of cells Standard Deviation 0.707	-3.00 percentage of cells
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Acute Follow-up: 145-168 hours	-2.00 percentage of cells Standard Deviation 1.414	-3.00 percentage of cells
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 8	0.50 percentage of cells Standard Deviation 2.121	—
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 15	2.00 percentage of cells Standard Deviation 1.414	—
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 22	1.00 percentage of cells Standard Deviation 2.828	-1.00 percentage of cells
Change From Baseline in Hematology Parameter: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 29	1.50 percentage of cells Standard Deviation 0.707	—

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in erythrocytes mean corpuscular hemoglobin concentration levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels Baseline	328.4 g/L Standard Deviation 12.54	322.6 g/L Standard Deviation 12.54
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Infusion: 0-24 hours	-1.2 g/L Standard Deviation 12.52	1.0 g/L Standard Deviation 5.66
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Infusion: 25-48 hours	-4.7 g/L Standard Deviation 10.43	10.4 g/L Standard Deviation 12.18
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Infusion: 49-72 hours	-3.4 g/L Standard Deviation 7.88	5.4 g/L Standard Deviation 6.19
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Infusion: 73-96 hours	-3.6 g/L Standard Deviation 10.00	3.6 g/L Standard Deviation 6.35
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Infusion: 97-120 hours	-4.1 g/L Standard Deviation 9.33	1.8 g/L Standard Deviation 3.03
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Acute Follow-up: 121-144 hours	-6.1 g/L Standard Deviation 10.65	-0.4 g/L Standard Deviation 2.61
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Acute Follow-up: 145-168 hours	-7.6 g/L Standard Deviation 10.44	0.4 g/L Standard Deviation 5.50
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Extended Follow-up: Day 8	-7.7 g/L Standard Deviation 11.07	-2.3 g/L Standard Deviation 9.54
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Extended Follow-up: Day 15	-5.5 g/L Standard Deviation 14.28	-0.5 g/L Standard Deviation 13.77
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Extended Follow-up: Day 22	-6.9 g/L Standard Deviation 18.40	11.5 g/L Standard Deviation 32.25
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration Levels CFB at Extended Follow-up: Day 29	-4.6 g/L Standard Deviation 16.10	-9.3 g/L Standard Deviation 7.50

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in erythrocytes mean corpuscular hemoglobin levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels Baseline	1.8611 femtomoles (fmol) Standard Deviation 0.17564	1.8335 femtomoles (fmol) Standard Deviation 0.09869
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Infusion: 0-24 hours	0.0110 femtomoles (fmol) Standard Deviation 0.04180	-0.0149 femtomoles (fmol) Standard Deviation 0.02996
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Infusion: 25-48 hours	-0.0134 femtomoles (fmol) Standard Deviation 0.03603	0.0261 femtomoles (fmol) Standard Deviation 0.09580
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Infusion: 49-72 hours	-0.0097 femtomoles (fmol) Standard Deviation 0.03719	0.0074 femtomoles (fmol) Standard Deviation 0.03911
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Infusion: 73-96 hours	-0.0107 femtomoles (fmol) Standard Deviation 0.04378	-0.0099 femtomoles (fmol) Standard Deviation 0.02177
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Infusion: 97-120 hours	-0.0164 femtomoles (fmol) Standard Deviation 0.04034	0.0112 femtomoles (fmol) Standard Deviation 0.03147
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Acute Follow-up: 121-144 hours	-0.0194 femtomoles (fmol) Standard Deviation 0.03684	0.0099 femtomoles (fmol) Standard Deviation 0.03582
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Acute Follow-up: 145-168 hours	-0.0112 femtomoles (fmol) Standard Deviation 0.04763	0.0161 femtomoles (fmol) Standard Deviation 0.03662
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Extended Follow-up: Day 8	-0.0058 femtomoles (fmol) Standard Deviation 0.04491	0.0155 femtomoles (fmol) Standard Deviation 0.04927
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Extended Follow-up: Day 15	-0.0087 femtomoles (fmol) Standard Deviation 0.09182	0.0310 femtomoles (fmol) Standard Deviation 0.07868
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Extended Follow-up: Day 22	-0.0306 femtomoles (fmol) Standard Deviation 0.14055	0.0729 femtomoles (fmol) Standard Deviation 0.14436
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Levels CFB at Extended Follow-up: Day 29	-0.0412 femtomoles (fmol) Standard Deviation 0.11506	0.0341 femtomoles (fmol) Standard Deviation 0.07457

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in erythrocytes mean corpuscular volume levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Infusion: 0-24 hours	0.68 femtoliters (fL) Standard Deviation 1.773	-0.42 femtoliters (fL) Standard Deviation 0.950
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Infusion: 25-48 hours	0.65 femtoliters (fL) Standard Deviation 2.202	-0.82 femtoliters (fL) Standard Deviation 1.487
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels Baseline	91.36 femtoliters (fL) Standard Deviation 7.651	91.50 femtoliters (fL) Standard Deviation 4.785
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Infusion: 49-72 hours	0.46 femtoliters (fL) Standard Deviation 2.168	-1.12 femtoliters (fL) Standard Deviation 1.314
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Infusion: 73-96 hours	0.38 femtoliters (fL) Standard Deviation 2.202	-1.04 femtoliters (fL) Standard Deviation 1.146
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Infusion: 97-120 hours	0.47 femtoliters (fL) Standard Deviation 2.560	0.10 femtoliters (fL) Standard Deviation 1.954
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Acute Follow-up: 121-144 hours	0.70 femtoliters (fL) Standard Deviation 2.362	0.76 femtoliters (fL) Standard Deviation 1.977
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Acute Follow-up: 145-168 hours	1.60 femtoliters (fL) Standard Deviation 3.270	0.36 femtoliters (fL) Standard Deviation 1.230
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Extended Follow-up: Day 8	1.30 femtoliters (fL) Standard Deviation 3.507	1.08 femtoliters (fL) Standard Deviation 1.090
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Extended Follow-up: Day 15	1.20 femtoliters (fL) Standard Deviation 4.337	2.25 femtoliters (fL) Standard Deviation 4.124
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Extended Follow-up: Day 22	0.29 femtoliters (fL) Standard Deviation 5.675	0.75 femtoliters (fL) Standard Deviation 3.747
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Levels CFB at Extended Follow-up: Day 29	-0.96 femtoliters (fL) Standard Deviation 5.315	4.27 femtoliters (fL) Standard Deviation 1.775

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in erythrocyte levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Erythrocyte Levels Baseline	3.261 10^6 cells per microliter Standard Deviation 0.7152	3.406 10^6 cells per microliter Standard Deviation 0.5297
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Infusion: 0-24 hours	-0.078 10^6 cells per microliter Standard Deviation 0.3236	-0.022 10^6 cells per microliter Standard Deviation 0.1816
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Infusion: 25-48 hours	-0.106 10^6 cells per microliter Standard Deviation 0.4059	-0.184 10^6 cells per microliter Standard Deviation 0.2799
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Infusion: 49-72 hours	-0.162 10^6 cells per microliter Standard Deviation 0.4112	-0.218 10^6 cells per microliter Standard Deviation 0.2072
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Infusion: 73-96 hours	-0.175 10^6 cells per microliter Standard Deviation 0.4261	-0.132 10^6 cells per microliter Standard Deviation 0.3041
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Infusion: 97-120 hours	-0.152 10^6 cells per microliter Standard Deviation 0.3718	-0.158 10^6 cells per microliter Standard Deviation 0.5079
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Acute Follow-up: 121-144 hours	-0.259 10^6 cells per microliter Standard Deviation 0.4001	-0.256 10^6 cells per microliter Standard Deviation 0.5786
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Acute Follow-up: 145-168 hours	-0.199 10^6 cells per microliter Standard Deviation 0.3819	-0.200 10^6 cells per microliter Standard Deviation 0.7139
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Extended Follow-up: Day 8	-0.196 10^6 cells per microliter Standard Deviation 0.4508	-0.463 10^6 cells per microliter Standard Deviation 0.4367
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Extended Follow-up: Day 15	0.115 10^6 cells per microliter Standard Deviation 0.7317	-0.133 10^6 cells per microliter Standard Deviation 0.5821
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Extended Follow-up: Day 22	0.285 10^6 cells per microliter Standard Deviation 0.9424	0.105 10^6 cells per microliter Standard Deviation 0.3493
Change From Baseline in Hematology Parameter: Erythrocyte Levels CFB at Extended Follow-up: Day 29	0.607 10^6 cells per microliter Standard Deviation 0.4754	0.248 10^6 cells per microliter Standard Deviation 0.2924

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in hematocrit levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Hematocrit Levels Baseline	0.2955 proportion of 1.0 (in liters) Standard Deviation 0.05601	0.3110 proportion of 1.0 (in liters) Standard Deviation 0.05443
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Infusion: 0-24 hours	-0.0042 proportion of 1.0 (in liters) Standard Deviation 0.02561	-0.0028 proportion of 1.0 (in liters) Standard Deviation 0.01591
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Infusion: 25-48 hours	-0.0058 proportion of 1.0 (in liters) Standard Deviation 0.03430	-0.0192 proportion of 1.0 (in liters) Standard Deviation 0.02013
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Infusion: 49-72 hours	-0.0123 proportion of 1.0 (in liters) Standard Deviation 0.03371	-0.0238 proportion of 1.0 (in liters) Standard Deviation 0.01487
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Infusion: 73-96 hours	-0.0131 proportion of 1.0 (in liters) Standard Deviation 0.03564	-0.0142 proportion of 1.0 (in liters) Standard Deviation 0.02860
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Infusion: 97-120 hours	-0.0108 proportion of 1.0 (in liters) Standard Deviation 0.03167	-0.0160 proportion of 1.0 (in liters) Standard Deviation 0.04813
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Acute Follow-up: 121-144 hours	-0.0209 proportion of 1.0 (in liters) Standard Deviation 0.03369	-0.0238 proportion of 1.0 (in liters) Standard Deviation 0.05369
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Acute Follow-up: 145-168 hours	-0.0135 proportion of 1.0 (in liters) Standard Deviation 0.03487	-0.0182 proportion of 1.0 (in liters) Standard Deviation 0.06883
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Extended Follow-up: Day 8	-0.0142 proportion of 1.0 (in liters) Standard Deviation 0.03823	-0.0375 proportion of 1.0 (in liters) Standard Deviation 0.04888
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Extended Follow-up: Day 15	0.0143 proportion of 1.0 (in liters) Standard Deviation 0.05903	-0.0058 proportion of 1.0 (in liters) Standard Deviation 0.05967
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Extended Follow-up: Day 22	0.0188 proportion of 1.0 (in liters) Standard Deviation 0.06186	0.0128 proportion of 1.0 (in liters) Standard Deviation 0.03157
Change From Baseline in Hematology Parameter: Hematocrit Levels CFB at Extended Follow-up: Day 29	0.0516 proportion of 1.0 (in liters) Standard Deviation 0.04241	0.0370 proportion of 1.0 (in liters) Standard Deviation 0.02670

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in hemoglobin levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Hemoglobin Levels Baseline	97.3 g/L Standard Deviation 19.93	100.4 g/L Standard Deviation 18.28
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Infusion: 0-24 hours	-2.1 g/L Standard Deviation 9.96	-0.8 g/L Standard Deviation 5.26
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Infusion: 25-48 hours	-3.8 g/L Standard Deviation 11.81	-3.4 g/L Standard Deviation 4.77
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Infusion: 49-72 hours	-5.2 g/L Standard Deviation 12.37	-5.8 g/L Standard Deviation 4.21
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Infusion: 73-96 hours	-5.8 g/L Standard Deviation 12.89	-4.0 g/L Standard Deviation 7.97
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Infusion: 97-120 hours	-5.4 g/L Standard Deviation 11.54	-4.4 g/L Standard Deviation 14.99
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Acute Follow-up: 121-144 hours	-8.8 g/L Standard Deviation 12.69	-7.2 g/L Standard Deviation 16.75
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Acute Follow-up: 145-168 hours	-6.8 g/L Standard Deviation 12.78	-5.6 g/L Standard Deviation 20.67
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Extended Follow-up: Day 8	-6.7 g/L Standard Deviation 14.41	-12.3 g/L Standard Deviation 12.97
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Extended Follow-up: Day 15	2.7 g/L Standard Deviation 22.10	-2.0 g/L Standard Deviation 18.65
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Extended Follow-up: Day 22	3.8 g/L Standard Deviation 21.36	8.3 g/L Standard Deviation 12.58
Change From Baseline in Hematology Parameter: Hemoglobin Levels CFB at Extended Follow-up: Day 29	15.3 g/L Standard Deviation 14.50	9.5 g/L Standard Deviation 9.26

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in leukocyte levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Leukocyte Levels Baseline	11.383 10^3 cells/uL Standard Deviation 4.3503	16.538 10^3 cells/uL Standard Deviation 8.5348
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Infusion: 0-24 hours	1.438 10^3 cells/uL Standard Deviation 2.5891	-0.902 10^3 cells/uL Standard Deviation 2.4833
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Infusion: 25-48 hours	0.186 10^3 cells/uL Standard Deviation 4.5526	-3.306 10^3 cells/uL Standard Deviation 4.7047
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Infusion: 49-72 hours	-0.227 10^3 cells/uL Standard Deviation 6.1765	-3.090 10^3 cells/uL Standard Deviation 5.5029
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Infusion: 73-96 hours	-0.577 10^3 cells/uL Standard Deviation 7.1508	-3.798 10^3 cells/uL Standard Deviation 5.5846
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Infusion: 97-120 hours	0.591 10^3 cells/uL Standard Deviation 10.3636	-3.964 10^3 cells/uL Standard Deviation 5.3646
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Acute Follow-up: 121-144 hours	-1.002 10^3 cells/uL Standard Deviation 8.9938	-1.306 10^3 cells/uL Standard Deviation 7.5940
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Acute Follow-up: 145-168 hours	-0.123 10^3 cells/uL Standard Deviation 10.4153	-1.652 10^3 cells/uL Standard Deviation 7.3674
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Extended Follow-up: Day 8	-1.145 10^3 cells/uL Standard Deviation 7.3294	-2.188 10^3 cells/uL Standard Deviation 6.7041
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Extended Follow-up: Day 15	-1.692 10^3 cells/uL Standard Deviation 5.0282	-6.118 10^3 cells/uL Standard Deviation 7.0178
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Extended Follow-up: Day 22	-1.132 10^3 cells/uL Standard Deviation 4.3853	-7.248 10^3 cells/uL Standard Deviation 7.3886
Change From Baseline in Hematology Parameter: Leukocyte Levels CFB at Extended Follow-up: Day 29	-0.790 10^3 cells/uL Standard Deviation 6.1582	-5.840 10^3 cells/uL Standard Deviation 4.6825

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in lymphocyte levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Lymphocyte Levels Baseline	1.791 10^3 cells/uL Standard Deviation 0.8043	2.323 10^3 cells/uL Standard Deviation 0.5193
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Infusion: 0-24 hours	0.213 10^3 cells/uL Standard Deviation 0.8923	-0.470 10^3 cells/uL Standard Deviation 0.2427
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Infusion: 25-48 hours	0.189 10^3 cells/uL Standard Deviation 1.3559	-1.147 10^3 cells/uL Standard Deviation 0.9771
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Infusion: 49-72 hours	0.302 10^3 cells/uL Standard Deviation 1.0584	-0.640 10^3 cells/uL Standard Deviation 1.1037
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Infusion: 73-96 hours	0.200 10^3 cells/uL Standard Deviation 1.1580	-0.780 10^3 cells/uL Standard Deviation 0.4358
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Infusion: 97-120 hours	0.428 10^3 cells/uL Standard Deviation 1.1946	-0.777 10^3 cells/uL Standard Deviation 0.6516
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Acute Follow-up: 121-144 hours	0.152 10^3 cells/uL Standard Deviation 0.9193	-0.987 10^3 cells/uL Standard Deviation 1.0040
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Acute Follow-up: 145-168 hours	0.360 10^3 cells/uL Standard Deviation 0.8965	-1.013 10^3 cells/uL Standard Deviation 0.8799
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Extended Follow-up: Day 8	0.482 10^3 cells/uL Standard Deviation 0.8724	-0.700 10^3 cells/uL Standard Deviation 0.6720
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Extended Follow-up: Day 15	0.392 10^3 cells/uL Standard Deviation 0.8363	-1.140 10^3 cells/uL Standard Deviation 0.9334
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Extended Follow-up: Day 22	0.343 10^3 cells/uL Standard Deviation 0.6667	-2.200 10^3 cells/uL
Change From Baseline in Hematology Parameter: Lymphocyte Levels CFB at Extended Follow-up: Day 29	0.427 10^3 cells/uL Standard Deviation 0.8182	-0.845 10^3 cells/uL Standard Deviation 1.0677

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in lymphocytes to leukocytes ratio is reported in terms of percentage of cells in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells Baseline	10.67 percentage of cells Standard Deviation 7.024	6.50 percentage of cells Standard Deviation 7.778
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 0-24 hours	-1.00 percentage of cells Standard Deviation 0.000	4.00 percentage of cells
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 25-48 hours	-2.50 percentage of cells Standard Deviation 2.121	8.00 percentage of cells
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 49-72 hours	0.67 percentage of cells Standard Deviation 5.033	10.00 percentage of cells
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 73-96 hours	-5.50 percentage of cells Standard Deviation 4.950	6.00 percentage of cells
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 97-120 hours	-4.50 percentage of cells Standard Deviation 6.364	8.00 percentage of cells
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Acute Follow-up: 121-144 hours	-6.00 percentage of cells Standard Deviation 4.243	1.00 percentage of cells
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Acute Follow-up: 145-168 hours	-6.00 percentage of cells Standard Deviation 2.828	1.00 percentage of cells
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 8	-6.00 percentage of cells Standard Deviation 1.414	—
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 15	-3.50 percentage of cells Standard Deviation 3.536	—
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 22	7.00 percentage of cells Standard Deviation 4.243	11.00 percentage of cells
Change From Baseline in Hematology Parameter: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 29	0.50 percentage of cells Standard Deviation 2.121	—

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in monocyte levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Monocyte Levels Baseline	0.6182 10^3 cells/uL Standard Deviation 0.26966	1.2567 10^3 cells/uL Standard Deviation 0.83584
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Infusion: 0-24 hours	0.2720 10^3 cells/uL Standard Deviation 0.39137	0.3470 10^3 cells/uL Standard Deviation 0.83703
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Infusion: 25-48 hours	0.2830 10^3 cells/uL Standard Deviation 0.54878	-0.1200 10^3 cells/uL Standard Deviation 1.05399
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Infusion: 49-72 hours	0.1267 10^3 cells/uL Standard Deviation 0.52906	-0.0667 10^3 cells/uL Standard Deviation 0.06110
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Infusion: 73-96 hours	0.2978 10^3 cells/uL Standard Deviation 0.44409	0.4533 10^3 cells/uL Standard Deviation 0.39068
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Infusion: 97-120 hours	0.2322 10^3 cells/uL Standard Deviation 0.42364	0.1300 10^3 cells/uL Standard Deviation 0.96016
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Acute Follow-up: 121-144 hours	0.2856 10^3 cells/uL Standard Deviation 0.47710	-0.1400 10^3 cells/uL Standard Deviation 0.34176
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Acute Follow-up: 145-168 hours	0.2800 10^3 cells/uL Standard Deviation 0.39418	-0.4533 10^3 cells/uL Standard Deviation 0.36295
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Extended Follow-up: Day 8	0.1900 10^3 cells/uL Standard Deviation 0.24850	-0.2400 10^3 cells/uL Standard Deviation 0.72194
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Extended Follow-up: Day 15	0.1767 10^3 cells/uL Standard Deviation 0.41602	-0.1100 10^3 cells/uL Standard Deviation 1.99404
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Extended Follow-up: Day 22	0.3029 10^3 cells/uL Standard Deviation 0.63746	1.7000 10^3 cells/uL
Change From Baseline in Hematology Parameter: Monocyte Levels CFB at Extended Follow-up: Day 29	0.0414 10^3 cells/uL Standard Deviation 0.21396	0.4850 10^3 cells/uL Standard Deviation 0.44548

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in monocytes to leukocytes ratio is reported in terms of percentage of cells in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Acute Follow-up: 145-168 hours	-7.00 percentage of cells Standard Deviation 9.899	-2.00 percentage of cells
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 8	-3.00 percentage of cells Standard Deviation 8.485	—
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 15	-4.50 percentage of cells Standard Deviation 6.364	—
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 22	-2.50 percentage of cells Standard Deviation 4.950	0.00 percentage of cells
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 29	-5.50 percentage of cells Standard Deviation 9.192	—
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells Baseline	7.67 percentage of cells Standard Deviation 5.508	5.00 percentage of cells Standard Deviation 4.243
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 0-24 hours	2.00 percentage of cells Standard Deviation 0.000	1.00 percentage of cells
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 25-48 hours	-5.50 percentage of cells Standard Deviation 7.778	13.00 percentage of cells
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 49-72 hours	-2.33 percentage of cells Standard Deviation 0.577	15.00 percentage of cells
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 73-96 hours	-4.50 percentage of cells Standard Deviation 4.950	8.00 percentage of cells
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 97-120 hours	-6.50 percentage of cells Standard Deviation 9.192	8.00 percentage of cells
Change From Baseline in Hematology Parameter: Monocytes to Leukocytes Ratio Reported in Percentage of Cells CFB at Acute Follow-up: 121-144 hours	-6.50 percentage of cells Standard Deviation 9.192	-1.00 percentage of cells

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in neutrophil levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Extended Follow-up: Day 29	-1.590 10^3 cells/uL Standard Deviation 2.6196	-6.323 10^3 cells/uL Standard Deviation 3.8800
Change From Baseline in Hematology Parameter: Neutrophil Levels Baseline	7.957 10^3 cells/uL Standard Deviation 4.1505	13.863 10^3 cells/uL Standard Deviation 8.8017
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Infusion: 0-24 hours	0.152 10^3 cells/uL Standard Deviation 2.4078	-0.043 10^3 cells/uL Standard Deviation 1.7435
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Infusion: 25-48 hours	-0.552 10^3 cells/uL Standard Deviation 3.1815	-0.783 10^3 cells/uL Standard Deviation 2.9957
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Infusion: 49-72 hours	-1.406 10^3 cells/uL Standard Deviation 3.4517	-0.167 10^3 cells/uL Standard Deviation 7.0002
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Infusion: 73-96 hours	-1.727 10^3 cells/uL Standard Deviation 3.6351	-1.620 10^3 cells/uL Standard Deviation 6.0920
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Infusion: 97-120 hours	-0.743 10^3 cells/uL Standard Deviation 3.3970	-2.653 10^3 cells/uL Standard Deviation 5.7315
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Acute Follow-up: 121-144 hours	-1.848 10^3 cells/uL Standard Deviation 4.2871	-4.247 10^3 cells/uL Standard Deviation 6.7336
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Acute Follow-up: 145-168 hours	-1.440 10^3 cells/uL Standard Deviation 4.1338	-3.517 10^3 cells/uL Standard Deviation 7.8465
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Extended Follow-up: Day 8	-1.731 10^3 cells/uL Standard Deviation 4.4360	-1.953 10^3 cells/uL Standard Deviation 7.7993
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Extended Follow-up: Day 15	-2.372 10^3 cells/uL Standard Deviation 4.3518	-9.825 10^3 cells/uL Standard Deviation 6.9650
Change From Baseline in Hematology Parameter: Neutrophil Levels CFB at Extended Follow-up: Day 22	-0.877 10^3 cells/uL Standard Deviation 3.2310	-10.645 10^3 cells/uL Standard Deviation 7.9832

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in neutrophils to leukocytes ratio is reported in terms of percentage of cells in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells Baseline	75.67 percentage of cells Standard Deviation 11.240	71.00 percentage of cells Standard Deviation 8.485
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 0-24 hours	-3.50 percentage of cells Standard Deviation 9.192	19.00 percentage of cells
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 25-48 hours	5.00 percentage of cells Standard Deviation 5.657	6.00 percentage of cells
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 49-72 hours	5.67 percentage of cells Standard Deviation 10.504	3.00 percentage of cells
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 73-96 hours	11.00 percentage of cells Standard Deviation 11.314	2.00 percentage of cells
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Infusion: 97-120 hours	13.50 percentage of cells Standard Deviation 17.678	9.00 percentage of cells
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Acute Follow-up: 121-144 hours	15.00 percentage of cells Standard Deviation 14.142	31.00 percentage of cells
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Acute Follow-up: 145-168 hours	11.00 percentage of cells Standard Deviation 8.485	25.00 percentage of cells
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 8	11.00 percentage of cells Standard Deviation 11.314	—
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 15	7.50 percentage of cells Standard Deviation 9.192	—
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 22	-4.00 percentage of cells Standard Deviation 7.071	-10.00 percentage of cells
Change From Baseline in Hematology Parameter: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells CFB at Extended Follow-up: Day 29	6.50 percentage of cells Standard Deviation 14.849	—

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes mean corpuscular hemoglobin concentration, erythrocytes mean corpuscular hemoglobin, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets. CFB in platelet levels is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Hematology Parameter: Platelet Levels Baseline	260.76 10^3 cells/uL Standard Deviation 95.417	284.20 10^3 cells/uL Standard Deviation 80.707
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Infusion: 0-24 hours	2.93 10^3 cells/uL Standard Deviation 68.821	21.40 10^3 cells/uL Standard Deviation 40.265
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Infusion: 25-48 hours	17.38 10^3 cells/uL Standard Deviation 92.854	34.40 10^3 cells/uL Standard Deviation 69.263
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Infusion: 49-72 hours	21.59 10^3 cells/uL Standard Deviation 109.995	58.00 10^3 cells/uL Standard Deviation 95.533
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Infusion: 73-96 hours	31.92 10^3 cells/uL Standard Deviation 112.963	77.80 10^3 cells/uL Standard Deviation 89.461
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Infusion: 97-120 hours	57.49 10^3 cells/uL Standard Deviation 125.277	64.80 10^3 cells/uL Standard Deviation 101.043
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Acute Follow-up: 121-144 hours	63.04 10^3 cells/uL Standard Deviation 138.415	61.80 10^3 cells/uL Standard Deviation 106.767
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Acute Follow-up: 145-168 hours	81.98 10^3 cells/uL Standard Deviation 141.650	50.80 10^3 cells/uL Standard Deviation 130.555
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Extended Follow-up: Day 8	58.33 10^3 cells/uL Standard Deviation 120.436	48.75 10^3 cells/uL Standard Deviation 136.231
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Extended Follow-up: Day 15	153.89 10^3 cells/uL Standard Deviation 166.919	87.25 10^3 cells/uL Standard Deviation 177.265
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Extended Follow-up: Day 22	86.35 10^3 cells/uL Standard Deviation 204.827	49.75 10^3 cells/uL Standard Deviation 75.292
Change From Baseline in Hematology Parameter: Platelet Levels CFB at Extended Follow-up: Day 29	25.76 10^3 cells/uL Standard Deviation 118.996	56.75 10^3 cells/uL Standard Deviation 112.512

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

ECG measures included heart rate, PR interval, QT interval, QRS duration and QTc interval. CFB in heart rate is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate Baseline	84.3 beats/min Standard Deviation 13.31	84.3 beats/min Standard Deviation 19.64
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Infusion: 0-24 hours	-1.4 beats/min Standard Deviation 16.87	-6.8 beats/min Standard Deviation 8.54
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Infusion: 25-48 hours	-0.9 beats/min Standard Deviation 16.58	-1.2 beats/min Standard Deviation 6.85
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Infusion: 49-72 hours	10.9 beats/min Standard Deviation 21.74	-6.5 beats/min Standard Deviation 22.28
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Infusion: 73-96 hours	9.7 beats/min Standard Deviation 15.49	7.7 beats/min Standard Deviation 18.48
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Infusion: 97-120 hours	15.9 beats/min Standard Deviation 15.37	7.0 beats/min Standard Deviation 19.62
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Acute Follow-up: 121-144 hours	13.2 beats/min Standard Deviation 14.25	11.7 beats/min Standard Deviation 22.76
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Acute Follow-up: 145-168 hours	16.6 beats/min Standard Deviation 16.91	17.0 beats/min Standard Deviation 26.47
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Extended Follow-up: Day 8	19.2 beats/min Standard Deviation 16.00	5.5 beats/min Standard Deviation 22.87
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Extended Follow-up: Day 15	15.0 beats/min Standard Deviation 23.09	5.5 beats/min Standard Deviation 13.13
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Extended Follow-up: Day 22	13.8 beats/min Standard Deviation 20.71	4.3 beats/min Standard Deviation 26.73
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate CFB at Extended Follow-up: Day 29	8.6 beats/min Standard Deviation 13.60	7.0 beats/min Standard Deviation 31.19

PRIMARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

ECG measures included heart rate, PR interval, QT interval, QRS duration and QTc interval. CFB in PR interval, QT interval, QRS duration and QTc interval is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: Baseline	151.0 milliseconds (msec) Interval 118.0 to 192.0	151.0 milliseconds (msec) Interval 132.0 to 182.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Infusion: 0-24 hours	2.0 milliseconds (msec) Interval -40.0 to 10.0	-2.0 milliseconds (msec) Interval -16.0 to 18.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Infusion: 25-48 hours	3.0 milliseconds (msec) Interval -40.0 to 148.0	3.0 milliseconds (msec) Interval -4.0 to 15.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Infusion: 49-72 hours	-13.0 milliseconds (msec) Interval -42.0 to 16.0	-2.0 milliseconds (msec) Interval -8.0 to 18.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Infusion: 73-96 hours	-2.0 milliseconds (msec) Interval -22.0 to 22.0	-4.0 milliseconds (msec) Interval -6.0 to 7.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Infusion: 97-120 hours	-12.0 milliseconds (msec) Interval -32.0 to 68.0	2.0 milliseconds (msec) Interval -22.0 to 26.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Acute Follow-up: 121-144 hours	-8.0 milliseconds (msec) Interval -25.0 to 23.0	3.5 milliseconds (msec) Interval -28.0 to 12.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Acute Follow-up: 145-168 hours	-11.0 milliseconds (msec) Interval -38.0 to 14.0	-2.0 milliseconds (msec) Interval -26.0 to 24.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Extended Follow-up: Day 8	-10.0 milliseconds (msec) Interval -30.0 to 4.0	0.0 milliseconds (msec) Interval -20.0 to 2.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Extended Follow-up: Day 15	0.0 milliseconds (msec) Interval -54.0 to 26.0	4.0 milliseconds (msec) Interval -16.0 to 18.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Extended Follow-up: Day 22	2.0 milliseconds (msec) Interval -26.0 to 36.0	-6.5 milliseconds (msec) Interval -40.0 to 10.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval PR interval: CFB at Extended Follow-up: Day 29	2.0 milliseconds (msec) Interval -20.0 to 14.0	-8.0 milliseconds (msec) Interval -18.0 to 22.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: Baseline	85.0 milliseconds (msec) Interval 66.0 to 118.0	78.0 milliseconds (msec) Interval 40.0 to 100.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Infusion: 0-24 hours	1.0 milliseconds (msec) Interval -12.0 to 14.0	1.5 milliseconds (msec) Interval -4.0 to 20.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Infusion: 25-48 hours	0.0 milliseconds (msec) Interval -14.0 to 40.0	-1.0 milliseconds (msec) Interval -8.0 to 6.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Infusion: 49-72 hours	-3.0 milliseconds (msec) Interval -20.0 to 6.0	2.0 milliseconds (msec) Interval -2.0 to 5.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Infusion: 73-96 hours	0.0 milliseconds (msec) Interval -16.0 to 18.0	0.0 milliseconds (msec) Interval -6.0 to 20.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Infusion: 97-120 hours	-4.0 milliseconds (msec) Interval -32.0 to 14.0	0.0 milliseconds (msec) Interval -14.0 to 20.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Acute Follow-up: 121-144 hours	-2.0 milliseconds (msec) Interval -32.0 to 8.0	0.0 milliseconds (msec) Interval -14.0 to 20.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Acute Follow-up: 145-168 hours	-6.0 milliseconds (msec) Interval -28.0 to 16.0	-3.0 milliseconds (msec) Interval -94.0 to 20.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Extended Follow-up: Day 8	-2.0 milliseconds (msec) Interval -28.0 to 0.0	-3.5 milliseconds (msec) Interval -16.0 to 0.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Extended Follow-up: Day 15	-5.0 milliseconds (msec) Interval -47.0 to 6.0	2.0 milliseconds (msec) Interval -2.0 to 40.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Extended Follow-up: Day 22	-4.0 milliseconds (msec) Interval -26.0 to 6.0	-1.0 milliseconds (msec) Interval -4.0 to 20.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QRS Interval: CFB at Extended Follow-up: Day 29	2.0 milliseconds (msec) Interval -26.0 to 12.0	5.0 milliseconds (msec) Interval -4.0 to 40.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: Baseline	363.0 milliseconds (msec) Interval 304.0 to 476.0	372.0 milliseconds (msec) Interval 280.0 to 462.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Infusion: 0-24 hours	19.5 milliseconds (msec) Interval -84.0 to 200.0	24.5 milliseconds (msec) Interval -26.0 to 49.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Infusion: 25-48 hours	19.5 milliseconds (msec) Interval -102.0 to 236.0	3.0 milliseconds (msec) Interval -40.0 to 30.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Infusion: 49-72 hours	1.0 milliseconds (msec) Interval -168.0 to 238.0	-14.0 milliseconds (msec) Interval -66.0 to 144.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Infusion: 73-96 hours	-4.0 milliseconds (msec) Interval -62.0 to 128.0	0.0 milliseconds (msec) Interval -76.0 to 118.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Infusion: 97-120 hours	-34.0 milliseconds (msec) Interval -164.0 to 72.0	-36.0 milliseconds (msec) Interval -102.0 to 66.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Acute Follow-up: 121-144 hours	-28.0 milliseconds (msec) Interval -168.0 to 238.0	-32.0 milliseconds (msec) Interval -126.0 to 40.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Acute Follow-up: 145-168 hours	-32.0 milliseconds (msec) Interval -164.0 to 74.0	-34.0 milliseconds (msec) Interval -156.0 to 18.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Extended Follow-up: Day 8	-36.0 milliseconds (msec) Interval -186.0 to 42.0	-35.0 milliseconds (msec) Interval -138.0 to -6.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Extended Follow-up: Day 15	-32.0 milliseconds (msec) Interval -176.0 to 72.0	-8.0 milliseconds (msec) Interval -116.0 to 16.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Extended Follow-up: Day 22	-28.0 milliseconds (msec) Interval -132.0 to 51.0	-22.0 milliseconds (msec) Interval -102.0 to 24.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QT Interval: CFB at Extended Follow-up: Day 29	-28.0 milliseconds (msec) Interval -132.0 to 29.0	-63.0 milliseconds (msec) Interval -96.0 to 80.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: Baseline	435.5 milliseconds (msec) Interval 321.0 to 531.0	438.5 milliseconds (msec) Interval 393.0 to 454.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Infusion: 0-24 hours	7.5 milliseconds (msec) Interval -55.0 to 219.0	7.0 milliseconds (msec) Interval -58.0 to 42.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Infusion: 25-48 hours	11.5 milliseconds (msec) Interval -49.0 to 277.0	-12.5 milliseconds (msec) Interval -59.0 to 29.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Infusion: 49-72 hours	3.5 milliseconds (msec) Interval -103.0 to 275.0	-14.0 milliseconds (msec) Interval -38.0 to 36.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Infusion: 73-96 hours	8.0 milliseconds (msec) Interval -30.0 to 145.0	-13.5 milliseconds (msec) Interval -41.0 to 152.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Infusion: 97-120 hours	-2.0 milliseconds (msec) Interval -88.0 to 106.0	-17.0 milliseconds (msec) Interval -38.0 to 43.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Acute Follow-up: 121-144 hours	-12.0 milliseconds (msec) Interval -87.0 to 319.0	-9.0 milliseconds (msec) Interval -31.0 to 10.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Acute Follow-up: 145-168 hours	-4.0 milliseconds (msec) Interval -96.0 to 93.0	-17.5 milliseconds (msec) Interval -52.0 to 15.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Extended Follow-up: Day 8	-15.0 milliseconds (msec) Interval -111.0 to 83.0	-54.5 milliseconds (msec) Interval -86.0 to 14.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Extended Follow-up: Day 15	2.0 milliseconds (msec) Interval -104.0 to 71.0	-6.5 milliseconds (msec) Interval -50.0 to 3.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Extended Follow-up: Day 22	-8.5 milliseconds (msec) Interval -57.0 to 51.0	-33.5 milliseconds (msec) Interval -37.0 to -14.0
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Interval, QT Interval and QTc Interval QTc Interval: CFB at Extended Follow-up: Day 29	-2.0 milliseconds (msec) Interval -72.0 to 51.0	-19.0 milliseconds (msec) Interval -51.0 to 23.0

PRIMARY outcome

Timeframe: Up to Day 29

Population: Safety population included all participants who were initiated with an infusion of SAGE-547.

Prior AEDs and Pressors are those medications that ended before the initiation of SAGE-547 infusion.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Number of Participants With Prior Anti-epileptic Drugs (AEDs) and Pressors Usage	16 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to Day 29

Relapse of participants is defined as successfully weaning from a continuous IV third-line agent but subsequent requirement of re-initiation of a third-line agent following conclusion of SAGE-547 treatment.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=16 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Number of Participants With Relapse - Re-Initiation of Third-Line Agent	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 96 hours

A responder was defined as a participant for whom it was not required to re-initiate continuous IV third-line therapy for refractory seizure control during the administration of SAGE-547 at the maintenance dose (prior to SAGE-547 taper infusion).

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=16 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Number of Participants With Treatment Response (Treatment Responders)	13 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to Day 29

Duration of response was defined as the time from the stop date/time of SAGE-547 maintenance to re-initiation of a third-line agent. If no re-initiation of a third-line agent was required, duration of response was not estimable and censored at Day 29 or death date, whichever occurred first. Kaplan-Meier method was used for the analysis.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=16 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Duration of Response	NA days Median and confidence interval were not calculable due to more than 50% censored participants (8) in this treatment group.	NA days Median and confidence interval were not calculable due to more than 50% censored participants (3) in this treatment group.

SECONDARY outcome

Timeframe: Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72, 96, 104, 112, 120 and 144 hours post-dose

Population: Pharmacokinetic (PK) population included all participants who received the study drug and had at least one PK sample taken. Overall number of participants analyzed is the number of participants with data available for analysis at the given time point for this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=18 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Maximum Plasma Concentration (Cmax) of SAGE-547	144.24 nanograms per milliliter (ng/mL) Standard Deviation 65.263	200.82 nanograms per milliliter (ng/mL) Standard Deviation 71.000

SECONDARY outcome

Timeframe: Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72, 96, 104, 112, 120 and 144 hours post-dose

Population: PK population included all participants who received the study drug and had at least one PK sample taken. Overall number of participants analyzed is the number of participants with data available for analysis at the given time point for this outcome measure.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=18 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Time to Attain Maximum Observed Plasma Concentration (Tmax) of SAGE-547	1.010 hours Interval 0.92 to 96.0	60.150 hours Interval 0.93 to 118.52

SECONDARY outcome

Timeframe: Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72, 96, 104, 112, 120 and 144 hours post-dose

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=17 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Areas Under the Plasma SAGE-547 Concentration Time Curves From the Start of the Infusion Until the Time to the Last Sample (AUClast)	7677.6 hournanograms per milliliter (hng/mL) Standard Deviation 2668.06	14260.0 hournanograms per milliliter (hng/mL) Standard Deviation 5048.01

SECONDARY outcome

Timeframe: Pre-dose (0 hours), 1, 2, 4, 8 and 24 hours post-dose

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=18 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Area Under the Plasma SAGE-547 Concentration-Time Curve in a 24 Hour Period (AUC24)	1590.3 h*ng/mL Standard Deviation 524.58	2728.3 h*ng/mL Standard Deviation 1010.14

SECONDARY outcome

Timeframe: Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72 and 96 hours post-dose

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=18 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Area Under the Plasma SAGE-547 Concentration-Time Curve (AUC1-96)	6290.6 h*ng/mL Standard Deviation 2080.04	10801.7 h*ng/mL Standard Deviation 4006.70

SECONDARY outcome

Timeframe: Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72 and 96 hours post-dose

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=18 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Average Plasma Concentration (Cav) of SAGE-547	66.22 ng/mL Standard Deviation 21.929	113.62 ng/mL Standard Deviation 42.079

SECONDARY outcome

Timeframe: Pre-dose (0 hours), 1, 2, 4, 8, 24, 48, 72, 96, 104, 112, 120 and 144 hours post-dose

Clearance is defined as the volume of plasma from which a substance is completely removed per unit time.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=17 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Plasma Clearance (CL) of SAGE-547	1.3999 liters per hour per kilogram (L/h/kg) Standard Deviation 0.54525	1.2487 liters per hour per kilogram (L/h/kg) Standard Deviation 0.65351

SECONDARY outcome

Timeframe: Baseline (Screening) to Infusion at 49-72 hour, 73-96 hour; Extended follow-up at Day 8, 15, 22 and 29

Population: Efficacy population included all participants who completed the SAGE-547 infusion and who had at least one attempt to wean the third-line agent(s) before the start of the taper of the SAGE-547 infusion. Number analyzed is the number of participants with data available for analyses at the given time point.

The mRS-9Q is a commonly used scale to determine disability and functional dependence due to neurological insult such as a stroke. It is a shortened version consisting of 9 questions. The score was categorized on the scale of 0 to 5 (0 = No symptoms, 1 = No significant disability, able to carry out all usual activities, despite some symptoms, 2 = Slight disability, able to look after own affairs without assistance, but unable to carry out all previous activities, 3 = Moderate disability, requires some help, but able to walk unassisted, 4 = Moderately severe disability, unable to attend to own bodily needs without assistance or unable to walk unassisted, and 5 = Severe disability, requires constant nursing care and attention, bedridden). Higher scores indicated worsening of symptoms.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=16 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Modified Rankin Scale (mRS-9Q) Scores CFB at Extended Follow-up: Day 29	-0.9 score on a scale Standard Deviation 1.50	-1.0 score on a scale Standard Deviation 1.41
Change From Baseline in Modified Rankin Scale (mRS-9Q) Scores Baseline	5.0 score on a scale Standard Deviation 0.00	5.0 score on a scale Standard Deviation 0.00
Change From Baseline in Modified Rankin Scale (mRS-9Q) Scores CBF at Infusion: 49-72 hours	0.0 score on a scale Standard Deviation 0.00	0.0 score on a scale Standard Deviation 0.00
Change From Baseline in Modified Rankin Scale (mRS-9Q) Scores CFB at Infusion: 73-96 hours	0.0 score on a scale Standard Deviation 0.00	0.0 score on a scale Standard Deviation 0.00
Change From Baseline in Modified Rankin Scale (mRS-9Q) Scores CFB at Extended Follow-up: Day 8	-0.1 score on a scale Standard Deviation 0.26	0.0 score on a scale Standard Deviation 0.00
Change From Baseline in Modified Rankin Scale (mRS-9Q) Scores CFB at Extended Follow-up: Day 15	-0.1 score on a scale Standard Deviation 0.35	-0.3 score on a scale Standard Deviation 0.50
Change From Baseline in Modified Rankin Scale (mRS-9Q) Scores CFB at Extended Follow-up: Day 22	-0.4 score on a scale Standard Deviation 0.74	-0.5 score on a scale Standard Deviation 0.58

SECONDARY outcome

Timeframe: Baseline (Screening), Extended follow-up at Days 8, 15, 22, and 29

The CGI-Severity (CGI-S) scale employs a 7-point Likert scale to assess the severity of participant's current illness state. Clinician responded to a question "Considering your total clinical experience with this particular population, how mentally ill is your patient at this time?" on the following scores: 1 = Normal, not at all ill, 2 = Borderline ill, 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severely ill, and 7 = Among the most extremely ill, where higher score = more affected.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=16 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Clinical Global Impression: Severity Scale (CGI-S) CFB at Extended Follow-up: Day 8	-1.1 score on a scale Standard Deviation 1.06	-1.2 score on a scale Standard Deviation 1.30
Change From Baseline in Clinical Global Impression: Severity Scale (CGI-S) CFB at Extended Follow-up: Day 15	-2.3 score on a scale Standard Deviation 1.22	-1.8 score on a scale Standard Deviation 1.79
Change From Baseline in Clinical Global Impression: Severity Scale (CGI-S) CFB at Extended Follow-up: Day 22	-2.7 score on a scale Standard Deviation 1.63	-2.4 score on a scale Standard Deviation 1.82
Change From Baseline in Clinical Global Impression: Severity Scale (CGI-S) Baseline	6.9 score on a scale Standard Deviation 0.25	6.8 score on a scale Standard Deviation 0.41
Change From Baseline in Clinical Global Impression: Severity Scale (CGI-S) CFB at Extended Follow-up: Day 29	-3.0 score on a scale Standard Deviation 1.96	-2.8 score on a scale Standard Deviation 2.39

SECONDARY outcome

Timeframe: Infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

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 included: 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; where higher scores indicated worst outcomes. The CGI-I was only rated at post-treatment assessments. By definition, all CGI-I assessments were evaluated against baseline conditions.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=16 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Clinical Global Impression: Improvement Scale (CGI-I) Scores Infusion: 0-24 hours	4.0 score on a scale Standard Deviation 0.37	4.0 score on a scale Standard Deviation 0.00
Clinical Global Impression: Improvement Scale (CGI-I) Scores Infusion: 25-48 hours	4.0 score on a scale Standard Deviation 0.52	4.5 score on a scale Standard Deviation 0.84
Clinical Global Impression: Improvement Scale (CGI-I) Scores Infusion: 49-72 hours	3.6 score on a scale Standard Deviation 0.81	3.6 score on a scale Standard Deviation 0.89
Clinical Global Impression: Improvement Scale (CGI-I) Scores Infusion: 73-96 hours	3.1 score on a scale Standard Deviation 0.81	3.7 score on a scale Standard Deviation 1.37
Clinical Global Impression: Improvement Scale (CGI-I) Scores Infusion: 97-120 hours	2.9 score on a scale Standard Deviation 0.81	3.0 score on a scale Standard Deviation 1.10
Clinical Global Impression: Improvement Scale (CGI-I) Scores Acute Follow-up: 121-144 hours	3.3 score on a scale Standard Deviation 1.30	4.0 score on a scale Standard Deviation 1.41
Clinical Global Impression: Improvement Scale (CGI-I) Scores Acute Follow-up: 145-168 hours	3.2 score on a scale Standard Deviation 1.52	3.2 score on a scale Standard Deviation 1.92
Clinical Global Impression: Improvement Scale (CGI-I) Scores Extended Follow-up: Day 8	2.9 score on a scale Standard Deviation 1.53	2.8 score on a scale Standard Deviation 1.10
Clinical Global Impression: Improvement Scale (CGI-I) Scores Extended Follow-up: Day 15	2.2 score on a scale Standard Deviation 1.21	2.4 score on a scale Standard Deviation 1.14
Clinical Global Impression: Improvement Scale (CGI-I) Scores Extended Follow-up: Day 22	2.3 score on a scale Standard Deviation 1.58	2.6 score on a scale Standard Deviation 1.95
Clinical Global Impression: Improvement Scale (CGI-I) Scores Extended Follow-up: Day 29	2.6 score on a scale Standard Deviation 1.89	2.4 score on a scale Standard Deviation 2.61

SECONDARY outcome

Timeframe: Baseline (Screening) to infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

The Glasgow Coma Scale is divided into three components which are scored separately: ocular response (assessment 1-4 points), motor response (assessment 1-6 points), verbal response (evaluation of 1-5 points). Scores for each component are added together to get the total score that will range between a minimum of 3 points (which corresponds to a participant who does not open his/her eyes and no motor response to stimulation or verbal response) and a maximum value of 15 points (corresponding to a participant with open eyes, obeying orders and maintaining a consistent language). It has been considered that the GCS score between 15 and 13 points corresponds to a slight alteration of consciousness, a score of 12-9 points with moderate impairment and 8 points or less with a serious deterioration in level of consciousness.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=16 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Glasgow Coma Scale (GCS) Scores Baseline	3.9 score on a scale Standard Deviation 1.88	3.5 score on a scale Standard Deviation 1.22
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Infusion: 0-24 hours	-0.4 score on a scale Standard Deviation 1.26	-0.2 score on a scale Standard Deviation 0.45
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Infusion: 25-48 hours	-0.6 score on a scale Standard Deviation 1.63	-0.5 score on a scale Standard Deviation 1.22
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Infusion: 49-72 hours	0.9 score on a scale Standard Deviation 2.21	1.4 score on a scale Standard Deviation 1.34
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Infusion: 73-96 hours	1.1 score on a scale Standard Deviation 2.16	1.3 score on a scale Standard Deviation 2.42
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Infusion: 97-120 hours	2.4 score on a scale Standard Deviation 3.16	3.0 score on a scale Standard Deviation 3.69
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Acute Follow-up: 121-144 hours	3.3 score on a scale Standard Deviation 3.30	3.3 score on a scale Standard Deviation 3.93
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Acute Follow-up: 145-168 hours	3.9 score on a scale Standard Deviation 3.98	5.0 score on a scale Standard Deviation 4.90
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Extended Follow-up: Day 8	3.9 score on a scale Standard Deviation 4.53	5.0 score on a scale Standard Deviation 4.90
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Extended Follow-up: Day 15	6.7 score on a scale Standard Deviation 4.73	5.4 score on a scale Standard Deviation 5.27
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Extended Follow-up: Day 22	6.9 score on a scale Standard Deviation 4.99	6.4 score on a scale Standard Deviation 4.83
Change From Baseline in Glasgow Coma Scale (GCS) Scores CFB at Extended Follow-up: Day 29	6.1 score on a scale Standard Deviation 5.70	7.4 score on a scale Standard Deviation 4.67

SECONDARY outcome

Timeframe: Baseline (Screening) to Infusion at 0-24, 25-48, 49-72, 73-96, 97-120 hours; Acute follow-up at 121-144, 145-168 hours; Extended follow-up at Days 8, 15, 22 and 29

The RASS was an assessment of agitation and sedation in hospitalized participants, using a 10 point scale (ranged from -5 to +4), where, -5 = Unarousable, -4 = Deep sedation, -3 = Moderate sedation, -2 = Light sedation, -1 = Drowsy, 0 = Alert and calm, +1 = Restless, +2 = Agitated, +3 = Very agitated and +4 = Combative. Lower scores signify higher levels of sedation and higher scores signify heightened agitation. Participant in a calm and alert state would score a 0.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=16 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score Baseline	-4.8 score on a scale Standard Deviation 0.54	-4.8 score on a scale Standard Deviation 0.41
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Infusion: 0-24 hours	-0.1 score on a scale Standard Deviation 0.25	0.0 score on a scale Standard Deviation 0.00
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Infusion: 25-48 hours	-0.1 score on a scale Standard Deviation 0.44	0.0 score on a scale Standard Deviation 0.00
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Infusion: 49-72 hours	0.5 score on a scale Standard Deviation 1.32	0.8 score on a scale Standard Deviation 1.30
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Infusion: 73-96 hours	0.9 score on a scale Standard Deviation 1.41	0.7 score on a scale Standard Deviation 1.21
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Infusion: 97-120 hours	1.4 score on a scale Standard Deviation 1.59	1.3 score on a scale Standard Deviation 1.75
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Acute Follow-up: 121-144 hours	2.0 score on a scale Standard Deviation 1.97	1.3 score on a scale Standard Deviation 1.97
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Acute Follow-up: 145-168 hours	2.3 score on a scale Standard Deviation 2.24	1.4 score on a scale Standard Deviation 1.67
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Extended Follow-up: Day 8	2.3 score on a scale Standard Deviation 2.16	2.4 score on a scale Standard Deviation 2.61
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Extended Follow-up: Day 15	3.3 score on a scale Standard Deviation 1.79	2.2 score on a scale Standard Deviation 1.92
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Extended Follow-up: Day 22	3.4 score on a scale Standard Deviation 1.91	2.8 score on a scale Standard Deviation 2.17
Change From Baseline in Richmond Agitation Sedation Scale (RASS) Score CFB at Extended Follow-up: Day 29	3.0 score on a scale Standard Deviation 2.22	2.8 score on a scale Standard Deviation 2.17

SECONDARY outcome

Timeframe: Up to Day 29

Survival time was defined as duration of survival from screening up to Day 29.

Outcome measures

Outcome measures
Measure	SAGE-547 Standard Dose n=16 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Number of Participants Who Survived	13 Participants	5 Participants

Adverse Events

SAGE-547 Standard Dose

Serious events: 14 serious events

Other events: 15 other events

Deaths: 5 deaths

SAGE-547 High Dose

Serious events: 2 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

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).
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Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Vital Sign Parameter: Heart Rate Baseline	89.3 beats per minute (beats/min) Standard Deviation 14.33	81.8 beats per minute (beats/min) Standard Deviation 20.90
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 0-24 hours: Loading - Pre-Dose	-2.3 beats per minute (beats/min) Standard Deviation 4.65	-0.5 beats per minute (beats/min) Standard Deviation 2.12
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 0-24 hours: Loading - 15 minutes	-0.7 beats per minute (beats/min) Standard Deviation 3.36	0.6 beats per minute (beats/min) Standard Deviation 1.52
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 0-24 hours: Loading - 30 minutes	0.2 beats per minute (beats/min) Standard Deviation 5.26	-2.0 beats per minute (beats/min) Standard Deviation 2.45
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 0-24 hours: Loading - 45 minutes	-0.9 beats per minute (beats/min) Standard Deviation 3.98	-3.6 beats per minute (beats/min) Standard Deviation 4.10
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 0-24 hours: 1 hour	-1.3 beats per minute (beats/min) Standard Deviation 4.18	-4.7 beats per minute (beats/min) Standard Deviation 7.26
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 0-24 hours: 2 hours	-1.6 beats per minute (beats/min) Standard Deviation 4.92	-0.5 beats per minute (beats/min) Standard Deviation 7.56
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 0-24 hours: 4 hours	-0.6 beats per minute (beats/min) Standard Deviation 7.65	-2.8 beats per minute (beats/min) Standard Deviation 8.52
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 0-24 hours: 8 hours	-3.5 beats per minute (beats/min) Standard Deviation 9.87	-10.7 beats per minute (beats/min) Standard Deviation 10.07
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 0-24 hours: 24 hours	-2.2 beats per minute (beats/min) Standard Deviation 13.52	1.8 beats per minute (beats/min) Standard Deviation 7.11
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 25-48 hours: 48 hours	1.9 beats per minute (beats/min) Standard Deviation 15.09	-4.8 beats per minute (beats/min) Standard Deviation 8.04
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 49-72 hours: 72 hours	5.4 beats per minute (beats/min) Standard Deviation 13.65	2.7 beats per minute (beats/min) Standard Deviation 12.42
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 73-96 hours: 96 hours	6.8 beats per minute (beats/min) Standard Deviation 14.03	8.0 beats per minute (beats/min) Standard Deviation 14.38
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Infusion: 97-120 hours: 120 hours	12.9 beats per minute (beats/min) Standard Deviation 13.43	10.7 beats per minute (beats/min) Standard Deviation 28.86
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Acute Follow-up: 121-144 hours	10.1 beats per minute (beats/min) Standard Deviation 13.10	18.0 beats per minute (beats/min) Standard Deviation 23.33
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Acute Follow-up: 145-168 hours	10.9 beats per minute (beats/min) Standard Deviation 15.77	14.8 beats per minute (beats/min) Standard Deviation 17.17
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Extended Follow-up: Day 8	11.8 beats per minute (beats/min) Standard Deviation 12.69	5.6 beats per minute (beats/min) Standard Deviation 15.34
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Extended Follow-up: Day 15	12.8 beats per minute (beats/min) Standard Deviation 15.66	6.0 beats per minute (beats/min) Standard Deviation 12.63
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Extended Follow-up: Day 22	13.3 beats per minute (beats/min) Standard Deviation 11.92	13.6 beats per minute (beats/min) Standard Deviation 27.88
Change From Baseline in Vital Sign Parameter: Heart Rate CFB at Extended Follow-up: Day 29	9.5 beats per minute (beats/min) Standard Deviation 16.19	11.2 beats per minute (beats/min) Standard Deviation 26.54

Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP Baseline	59.7 millimeters of mercury (mmHg) Standard Deviation 8.51	60.8 millimeters of mercury (mmHg) Standard Deviation 10.69
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Extended Follow-up: Day 8	1.1 millimeters of mercury (mmHg) Standard Deviation 12.40	1.0 millimeters of mercury (mmHg) Standard Deviation 10.89
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP Baseline	111.1 millimeters of mercury (mmHg) Standard Deviation 14.55	111.8 millimeters of mercury (mmHg) Standard Deviation 7.46
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 0-24 hours: Loading - Pre-Dose	1.3 millimeters of mercury (mmHg) Standard Deviation 13.23	20.0 millimeters of mercury (mmHg) Standard Deviation 28.28
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 0-24 hours: Loading - 15 minutes	-3.2 millimeters of mercury (mmHg) Standard Deviation 8.36	5.0 millimeters of mercury (mmHg) Standard Deviation 11.85
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 0-24 hours: Loading - 30 minutes	-4.3 millimeters of mercury (mmHg) Standard Deviation 12.64	3.8 millimeters of mercury (mmHg) Standard Deviation 11.12
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 0-24 hours: Loading - 45 minutes	-5.3 millimeters of mercury (mmHg) Standard Deviation 12.55	-9.4 millimeters of mercury (mmHg) Standard Deviation 12.22
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 0-24 hours: 1 hour	-7.4 millimeters of mercury (mmHg) Standard Deviation 11.96	-6.8 millimeters of mercury (mmHg) Standard Deviation 11.39
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 0-24 hours: 2 hours	-6.1 millimeters of mercury (mmHg) Standard Deviation 15.96	-5.7 millimeters of mercury (mmHg) Standard Deviation 19.72
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 0-24 hours: 4 hours	-1.1 millimeters of mercury (mmHg) Standard Deviation 14.40	-1.7 millimeters of mercury (mmHg) Standard Deviation 11.81
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 0-24 hours: 8 hours	-5.1 millimeters of mercury (mmHg) Standard Deviation 18.55	-1.3 millimeters of mercury (mmHg) Standard Deviation 18.02
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 0-24 hours: 24 hour	-5.6 millimeters of mercury (mmHg) Standard Deviation 19.26	5.7 millimeters of mercury (mmHg) Standard Deviation 17.63
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 25-48 hours: 48 hours	-3.1 millimeters of mercury (mmHg) Standard Deviation 21.49	2.5 millimeters of mercury (mmHg) Standard Deviation 21.55
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 49-72 hours: 72 hours	-2.1 millimeters of mercury (mmHg) Standard Deviation 27.72	3.0 millimeters of mercury (mmHg) Standard Deviation 23.83
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 73-96 hours: 96 hours	6.2 millimeters of mercury (mmHg) Standard Deviation 24.06	11.8 millimeters of mercury (mmHg) Standard Deviation 24.39
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Infusion: 97-120 hours: 120 hours	-6.9 millimeters of mercury (mmHg) Standard Deviation 22.13	-1.8 millimeters of mercury (mmHg) Standard Deviation 21.04
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Acute Follow-up: 121-144 hours	-2.2 millimeters of mercury (mmHg) Standard Deviation 18.67	12.8 millimeters of mercury (mmHg) Standard Deviation 21.58
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Acute Follow-up: 145-168 hours	-0.2 millimeters of mercury (mmHg) Standard Deviation 24.46	7.0 millimeters of mercury (mmHg) Standard Deviation 25.93
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Extended Follow-up: Day 8	-0.9 millimeters of mercury (mmHg) Standard Deviation 21.12	5.0 millimeters of mercury (mmHg) Standard Deviation 16.02
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Extended Follow-up: Day 15	8.9 millimeters of mercury (mmHg) Standard Deviation 19.55	3.2 millimeters of mercury (mmHg) Standard Deviation 11.52
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Extended Follow-up: Day 22	1.6 millimeters of mercury (mmHg) Standard Deviation 27.60	7.0 millimeters of mercury (mmHg) Standard Deviation 6.75
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP SBP CFB at Extended Follow-up: Day 29	2.0 millimeters of mercury (mmHg) Standard Deviation 24.20	2.8 millimeters of mercury (mmHg) Standard Deviation 19.77
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 0-24 hours: Loading - Pre-Dose	1.3 millimeters of mercury (mmHg) Standard Deviation 10.53	7.5 millimeters of mercury (mmHg) Standard Deviation 10.61
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 0-24 hours: Loading - 15 minutes	-2.1 millimeters of mercury (mmHg) Standard Deviation 5.83	2.2 millimeters of mercury (mmHg) Standard Deviation 4.15
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 0-24 hours: Loading - 30 minutes	-2.6 millimeters of mercury (mmHg) Standard Deviation 10.38	3.6 millimeters of mercury (mmHg) Standard Deviation 5.41
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 0-24 hours: Loading - 45 minutes	-3.3 millimeters of mercury (mmHg) Standard Deviation 6.26	-3.6 millimeters of mercury (mmHg) Standard Deviation 7.33
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 0-24 hours: 1 hour	-3.4 millimeters of mercury (mmHg) Standard Deviation 8.17	-1.8 millimeters of mercury (mmHg) Standard Deviation 3.25
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 0-24 hours: 2 hours	-2.8 millimeters of mercury (mmHg) Standard Deviation 6.70	-3.2 millimeters of mercury (mmHg) Standard Deviation 9.56
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 0-24 hours: 4 hours	-1.7 millimeters of mercury (mmHg) Standard Deviation 7.36	0.0 millimeters of mercury (mmHg) Standard Deviation 8.67
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 0-24 hours: 8 hours	-2.5 millimeters of mercury (mmHg) Standard Deviation 7.11	-5.0 millimeters of mercury (mmHg) Standard Deviation 12.17
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 0-24 hours: 24 hours	-2.9 millimeters of mercury (mmHg) Standard Deviation 12.61	6.3 millimeters of mercury (mmHg) Standard Deviation 24.99
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 25-48 hours: 48 hours	-2.9 millimeters of mercury (mmHg) Standard Deviation 9.01	-4.0 millimeters of mercury (mmHg) Standard Deviation 7.87
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 49-72 hours: 72 hours	-1.2 millimeters of mercury (mmHg) Standard Deviation 16.37	-4.2 millimeters of mercury (mmHg) Standard Deviation 5.42
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 73-96 hours: 96 hours	1.1 millimeters of mercury (mmHg) Standard Deviation 12.09	3.3 millimeters of mercury (mmHg) Standard Deviation 7.58
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Infusion: 97-120 hours: 120 hours	-3.4 millimeters of mercury (mmHg) Standard Deviation 12.65	1.0 millimeters of mercury (mmHg) Standard Deviation 12.13
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Acute Follow-up: 121-144 hours	-1.8 millimeters of mercury (mmHg) Standard Deviation 11.53	6.6 millimeters of mercury (mmHg) Standard Deviation 8.99
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Acute Follow-up: 145-168 hours	0.8 millimeters of mercury (mmHg) Standard Deviation 18.15	3.0 millimeters of mercury (mmHg) Standard Deviation 18.59
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Extended Follow-up: Day 15	7.9 millimeters of mercury (mmHg) Standard Deviation 11.13	4.8 millimeters of mercury (mmHg) Standard Deviation 6.22
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Extended Follow-up: Day 22	7.3 millimeters of mercury (mmHg) Standard Deviation 14.67	13.4 millimeters of mercury (mmHg) Standard Deviation 11.72
Change From Baseline in Vital Sign Parameter: Blood Pressure - SBP and DBP DBP CFB at Extended Follow-up: Day 29	7.9 millimeters of mercury (mmHg) Standard Deviation 11.02	12.4 millimeters of mercury (mmHg) Standard Deviation 22.78

Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 49-72 hours: 72 hours	1.6 breaths per min (breaths/min) Standard Deviation 3.65	1.0 breaths per min (breaths/min) Standard Deviation 6.96
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 73-96 hours: 96 hours	4.7 breaths per min (breaths/min) Standard Deviation 6.87	1.2 breaths per min (breaths/min) Standard Deviation 6.97
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Acute Follow-up: 145-168 hours	4.2 breaths per min (breaths/min) Standard Deviation 6.08	6.0 breaths per min (breaths/min) Standard Deviation 6.32
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Extended Follow-up: Day 15	3.7 breaths per min (breaths/min) Standard Deviation 5.87	5.0 breaths per min (breaths/min) Standard Deviation 6.40
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Extended Follow-up: Day 22	4.9 breaths per min (breaths/min) Standard Deviation 4.32	3.0 breaths per min (breaths/min) Standard Deviation 6.00
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Extended Follow-up: Day 29	3.5 breaths per min (breaths/min) Standard Deviation 6.35	5.6 breaths per min (breaths/min) Standard Deviation 11.28
Change From Baseline in Vital Sign Parameter: Respiratory Rate Baseline	17.4 breaths per min (breaths/min) Standard Deviation 4.66	13.4 breaths per min (breaths/min) Standard Deviation 3.58
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 0-24 hours: Loading - Pre-Dose	0.3 breaths per min (breaths/min) Standard Deviation 2.75	-2.0 breaths per min (breaths/min) Standard Deviation 1.41
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 0-24 hours: Loading - 15 minutes	0.2 breaths per min (breaths/min) Standard Deviation 2.39	-0.6 breaths per min (breaths/min) Standard Deviation 0.89
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 0-24 hours: Loading - 30 minutes	-0.3 breaths per min (breaths/min) Standard Deviation 3.05	-1.0 breaths per min (breaths/min) Standard Deviation 1.41
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 0-24 hours: Loading - 45 minutes	-0.3 breaths per min (breaths/min) Standard Deviation 2.64	1.0 breaths per min (breaths/min) Standard Deviation 2.65
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 0-24 hours: 1 hour	0.2 breaths per min (breaths/min) Standard Deviation 2.24	0.2 breaths per min (breaths/min) Standard Deviation 1.47
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 0-24 hours: 2 hours	1.1 breaths per min (breaths/min) Standard Deviation 2.78	0.8 breaths per min (breaths/min) Standard Deviation 1.33
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 0-24 hours: 4 hours	0.6 breaths per min (breaths/min) Standard Deviation 1.98	-0.2 breaths per min (breaths/min) Standard Deviation 1.33
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 0-24 hours: 8 hours	-0.5 breaths per min (breaths/min) Standard Deviation 2.14	-0.3 breaths per min (breaths/min) Standard Deviation 1.86
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 0-24 hours: 24 hours	0.3 breaths per min (breaths/min) Standard Deviation 4.08	0.7 breaths per min (breaths/min) Standard Deviation 1.51
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 25-48 hours: 48 hours	-0.1 breaths per min (breaths/min) Standard Deviation 3.21	-0.8 breaths per min (breaths/min) Standard Deviation 3.66
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Infusion: 97-120 hours: 120 hours	2.5 breaths per min (breaths/min) Standard Deviation 5.62	1.0 breaths per min (breaths/min) Standard Deviation 4.90
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Acute Follow-up: 121-144 hours	3.2 breaths per min (breaths/min) Standard Deviation 4.25	1.4 breaths per min (breaths/min) Standard Deviation 5.77
Change From Baseline in Vital Sign Parameter: Respiratory Rate CFB at Extended Follow-up: Day 8	4.3 breaths per min (breaths/min) Standard Deviation 5.94	0.6 breaths per min (breaths/min) Standard Deviation 3.05

Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Vital Sign Parameter: Body Temperature Baseline	99.21 degrees Fahrenheit (F) Standard Deviation 1.195	98.98 degrees Fahrenheit (F) Standard Deviation 2.312
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 0-24 hours: Loading - 30 minutes	-0.54 degrees Fahrenheit (F) Standard Deviation 0.628	-0.14 degrees Fahrenheit (F) Standard Deviation 0.371
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 0-24 hours: Loading - 45 minutes	-0.58 degrees Fahrenheit (F) Standard Deviation 0.662	-0.32 degrees Fahrenheit (F) Standard Deviation 0.432
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 0-24 hours: Loading - Pre-Dose	-0.80 degrees Fahrenheit (F) Standard Deviation 0.883	-0.30 degrees Fahrenheit (F) Standard Deviation 0.707
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 0-24 hours: Loading - 15 minutes	-0.38 degrees Fahrenheit (F) Standard Deviation 0.471	-0.04 degrees Fahrenheit (F) Standard Deviation 0.329
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 0-24 hours: 1 hour	-0.51 degrees Fahrenheit (F) Standard Deviation 0.614	-0.55 degrees Fahrenheit (F) Standard Deviation 0.468
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 0-24 hours: 2 hours	-0.44 degrees Fahrenheit (F) Standard Deviation 0.902	-0.48 degrees Fahrenheit (F) Standard Deviation 0.407
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 0-24 hours: 4 hours	-0.17 degrees Fahrenheit (F) Standard Deviation 1.269	-0.47 degrees Fahrenheit (F) Standard Deviation 0.596
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 0-24 hours: 8 hours	-0.74 degrees Fahrenheit (F) Standard Deviation 1.361	-0.52 degrees Fahrenheit (F) Standard Deviation 0.985
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 0-24 hours: 24 hours	-0.20 degrees Fahrenheit (F) Standard Deviation 1.704	0.20 degrees Fahrenheit (F) Standard Deviation 1.474
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 25-48 hours: 48 hours	-0.51 degrees Fahrenheit (F) Standard Deviation 1.467	-0.47 degrees Fahrenheit (F) Standard Deviation 1.335
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 49-72 hours: 72 hours	-0.53 degrees Fahrenheit (F) Standard Deviation 1.522	-0.47 degrees Fahrenheit (F) Standard Deviation 1.296
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 73-96 hour: 96 hours	-0.32 degrees Fahrenheit (F) Standard Deviation 1.263	-0.62 degrees Fahrenheit (F) Standard Deviation 1.283
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Infusion: 97-120 hours: 120 hours	-0.14 degrees Fahrenheit (F) Standard Deviation 1.230	-0.92 degrees Fahrenheit (F) Standard Deviation 1.514
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Acute Follow-up: 121-144 hours	0.06 degrees Fahrenheit (F) Standard Deviation 1.360	-0.16 degrees Fahrenheit (F) Standard Deviation 1.450
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Acute Follow-up: 145-168 hours	-0.29 degrees Fahrenheit (F) Standard Deviation 1.896	-0.20 degrees Fahrenheit (F) Standard Deviation 0.652
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Extended Follow-up: Day 8	0.03 degrees Fahrenheit (F) Standard Deviation 1.010	-0.46 degrees Fahrenheit (F) Standard Deviation 0.684
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Extended Follow-up: Day 15	-0.44 degrees Fahrenheit (F) Standard Deviation 1.852	-0.42 degrees Fahrenheit (F) Standard Deviation 0.740
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Extended Follow-up: Day 22	-0.62 degrees Fahrenheit (F) Standard Deviation 1.834	-0.96 degrees Fahrenheit (F) Standard Deviation 1.790
Change From Baseline in Vital Sign Parameter: Body Temperature CFB at Extended Follow-up: Day 29	-0.69 degrees Fahrenheit (F) Standard Deviation 1.515	-1.20 degrees Fahrenheit (F) Standard Deviation 2.164

Measure	SAGE-547 Standard Dose n=19 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 Participants Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 0-24 hours: Loading - 15 minutes	0.0 percentage of oxygen saturation Standard Deviation 0.33	0.2 percentage of oxygen saturation Standard Deviation 0.45
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Extended Follow-up: Day 22	-6.9 percentage of oxygen saturation Standard Deviation 22.32	0.6 percentage of oxygen saturation Standard Deviation 1.52
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Extended Follow-up: Day 29	-1.3 percentage of oxygen saturation Standard Deviation 3.54	-1.2 percentage of oxygen saturation Standard Deviation 1.30
Change From Baseline in Vital Sign Parameter: Oxygen Saturation Baseline	98.8 percentage of oxygen saturation Standard Deviation 2.26	98.6 percentage of oxygen saturation Standard Deviation 1.67
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 0-24 hours: Loading - Pre-Dose	0.0 percentage of oxygen saturation Standard Deviation 0.00	0.5 percentage of oxygen saturation Standard Deviation 0.71
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 0-24 hours: Loading - 30 minutes	-0.3 percentage of oxygen saturation Standard Deviation 1.45	0.4 percentage of oxygen saturation Standard Deviation 1.52
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 0-24 hours: Loading - 45 minutes	-0.2 percentage of oxygen saturation Standard Deviation 1.08	0.2 percentage of oxygen saturation Standard Deviation 1.92
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 0-24 hours: 1 hour	-0.5 percentage of oxygen saturation Standard Deviation 2.48	0.0 percentage of oxygen saturation Standard Deviation 1.55
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 0-24 hours: 2 hours	0.1 percentage of oxygen saturation Standard Deviation 1.10	-1.3 percentage of oxygen saturation Standard Deviation 4.76
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 0-24 hours: 4 hours	-0.2 percentage of oxygen saturation Standard Deviation 0.69	1.2 percentage of oxygen saturation Standard Deviation 1.33
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 0-24 hours: 8 hours	-0.1 percentage of oxygen saturation Standard Deviation 1.45	1.0 percentage of oxygen saturation Standard Deviation 0.89
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 0-24 hours: 24 hours	0.0 percentage of oxygen saturation Standard Deviation 1.15	-0.7 percentage of oxygen saturation Standard Deviation 1.75
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 25-48 hours: 48 hours	-0.6 percentage of oxygen saturation Standard Deviation 2.75	0.8 percentage of oxygen saturation Standard Deviation 0.98
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 49-72 hours: 72 hours	-0.1 percentage of oxygen saturation Standard Deviation 2.01	0.3 percentage of oxygen saturation Standard Deviation 1.97
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 73-96 hours: 96 hours	-0.3 percentage of oxygen saturation Standard Deviation 2.95	-0.8 percentage of oxygen saturation Standard Deviation 2.48
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Infusion: 97-120 hours: 120 hours	-0.5 percentage of oxygen saturation Standard Deviation 2.62	-1.3 percentage of oxygen saturation Standard Deviation 2.34
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Acute Follow-up: 121-144 hours	0.1 percentage of oxygen saturation Standard Deviation 2.11	0.0 percentage of oxygen saturation Standard Deviation 1.58
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Acute Follow-up: 145-168 hours	-0.3 percentage of oxygen saturation Standard Deviation 2.31	-0.8 percentage of oxygen saturation Standard Deviation 2.86
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Extended Follow-up: Day 8	-0.5 percentage of oxygen saturation Standard Deviation 2.58	-0.2 percentage of oxygen saturation Standard Deviation 1.64
Change From Baseline in Vital Sign Parameter: Oxygen Saturation CFB at Extended Follow-up: Day 15	-1.1 percentage of oxygen saturation Standard Deviation 2.90	0.4 percentage of oxygen saturation Standard Deviation 0.55

Measure	SAGE-547 Standard Dose n=19 participants at risk Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for 95 hours from Days 1 to 4 followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.	SAGE-547 High Dose n=6 participants at risk Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.
Respiratory, thoracic and mediastinal disorders Respiratory failure	15.8% 3/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	10.5% 2/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Infections and infestations Sepsis	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	16.7% 1/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Infections and infestations Peritonitis	0.00% 0/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	16.7% 1/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Infections and infestations Pneumonia	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Infections and infestations Tracheostomy infection	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Injury, poisoning and procedural complications Chemical poisoning	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Injury, poisoning and procedural complications Post procedural haemorrhage	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Injury, poisoning and procedural complications Wound dehiscence	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Nervous system disorders Convulsion	10.5% 2/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Nervous system disorders Critical illness polyneuropathy	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Vascular disorders Haemodynamic instability	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Vascular disorders Hypotension	0.00% 0/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	16.7% 1/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Vascular disorders Obstructive shock	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
General disorders Multi-organ failure	0.00% 0/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	16.7% 1/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
General disorders Pyrexia	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Metabolism and nutrition disorders Acidosis	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	16.7% 1/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Renal and urinary disorders Renal failure acute	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	16.7% 1/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Cardiac disorders Cardiac arrest	0.00% 0/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	16.7% 1/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Investigations Hepatic enzyme increased	5.3% 1/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	0.00% 0/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/19 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.	16.7% 1/6 • Up to 29 days Safety Population included all participants who were initiated with an infusion of SAGE-547.