Trial Outcomes & Findings for Evaluate SAGE-547 in Participants With Essential Tremor (NCT NCT02277106)

Results Overview

An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was defined as an AE with start date/time after the start of initial infusion in each stage. An SAE is defined as an AE or suspected adverse reaction, which in the view of either the Investigator or Sponsor, results in any of the following outcomes: death; is life-threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability or incapacity; congenital anomaly or birth defect or other medically important condition.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Stage 1: Up to 30 days after last infusion (up to Day 40)

Results posted on

2022-06-29

Participant Flow

Participants were enrolled at 2 investigative sites in the United States from 23 September 2014 to 14 August 2015.

This study consisted of two stages, Stages 1 and 2. Stage 1 had two periods with treatment on Days 1 and 10 and a 7-day follow-up period. Participants were followed for serious adverse events (SAEs) up to 30 days after the last dose. Stage 2 follows Stage 1, with treatment on Day 1 and a 7-day follow-up period thereafter.

Participant milestones

Participant milestones
Measure	Stage 1 (Double-blind): SAGE 547, Then Placebo Participants received a 12-hour intravenous (IV) infusion of SAGE 547, at ascending doses of 29, 58, and 86 micrograms per kilogram of body weight per hour (μg/kg/h), 4 hours each, on Day 1 of Stage 1 \[Treatment Period 1 (TP 1)\]. After a washout period of approximately 7 days, participants received a 12-hour IV infusion of SAGE-547 matching-placebo, on Day 10 of Stage 1 \[Treatment Period 2 (TP 2)\].	Stage 1 (Double-blind): Placebo, Then SAGE-547 Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1). After a washout period of approximately 7 days, participants received a 12-hour IV infusion of SAGE 547 at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 10 of Stage 1 (TP 2).	Stage 2 (Open Label): SAGE-547 Participants who completed Stage 1 were invited to receive a 10-hour IV infusion of SAGE 547, at ascending doses of 90 μg/kg/h for 1 hour, 120 μg/kg/h for 1 hour, and 150 μg/kg/h for 8 hours on Day 1 of Stage 2.
Stage 1: Treatment Period 1 STARTED	13	12	0
Stage 1: Treatment Period 1 COMPLETED	13	12	0
Stage 1: Treatment Period 1 NOT COMPLETED	0	0	0
Washout STARTED	13	12	0
Washout COMPLETED	13	12	0
Washout NOT COMPLETED	0	0	0
Stage 1: Treatment Period 2 STARTED	13	12	0
Stage 1: Treatment Period 2 COMPLETED	13	12	0
Stage 1: Treatment Period 2 NOT COMPLETED	0	0	0
Stage 2 STARTED	0	0	17
Stage 2 COMPLETED	0	0	16
Stage 2 NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Stage 1 (Double-blind): SAGE 547, Then Placebo Participants received a 12-hour intravenous (IV) infusion of SAGE 547, at ascending doses of 29, 58, and 86 micrograms per kilogram of body weight per hour (μg/kg/h), 4 hours each, on Day 1 of Stage 1 \[Treatment Period 1 (TP 1)\]. After a washout period of approximately 7 days, participants received a 12-hour IV infusion of SAGE-547 matching-placebo, on Day 10 of Stage 1 \[Treatment Period 2 (TP 2)\].	Stage 1 (Double-blind): Placebo, Then SAGE-547 Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1). After a washout period of approximately 7 days, participants received a 12-hour IV infusion of SAGE 547 at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 10 of Stage 1 (TP 2).	Stage 2 (Open Label): SAGE-547 Participants who completed Stage 1 were invited to receive a 10-hour IV infusion of SAGE 547, at ascending doses of 90 μg/kg/h for 1 hour, 120 μg/kg/h for 1 hour, and 150 μg/kg/h for 8 hours on Day 1 of Stage 2.
Stage 2 Adverse Event	0	0	1

Baseline Characteristics

Evaluate SAGE-547 in Participants With Essential Tremor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stage 1 (Double-blind): SAGE-547 and Placebo n=25 Participants Participants who received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1), received a 12-hour IV infusion of SAGE-547 matched-placebo, on Day 10 of Stage 1 (TP 2), after a washout period of approximately 7 days. Participants who received a 12-hour IV infusion of SAGE-547 matched-placebo on Day 1 of Stage 1 (TP 1), received a 12-hour IV infusion of SAGE 547 at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 10 of Stage 1 (TP 2), after a washout period of approximately 7 days.
Age, Continuous	64.2 years STANDARD_DEVIATION 5.7 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized White	22 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Stage 1: Up to 30 days after last infusion (up to Day 40)

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was defined as an AE with start date/time after the start of initial infusion in each stage. An SAE is defined as an AE or suspected adverse reaction, which in the view of either the Investigator or Sponsor, results in any of the following outcomes: death; is life-threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability or incapacity; congenital anomaly or birth defect or other medically important condition.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	12.0 percentage of participants	20.0 percentage of participants
Stage 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: Stage 2: Up to 30 days after last infusion (up to Day 31)

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was defined as an AE with start date/time after the start of initial infusion in each stage. An SAE is defined as an AE or suspected adverse reaction, which in the view of either the Investigator or Sponsor, results in any of the following outcomes: death; is life-threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability or incapacity; congenital anomaly or birth defect or other medically important condition.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	47.1 percentage of participants	—
Stage 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	0 percentage of participants	—

PRIMARY outcome

Timeframe: Stage 1: Pre-infusion on Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2)

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

The C-SSRS scale consisted of baseline evaluation that assessed lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and postbaseline evaluation that focused on suicidality since last study visit. C-SSRS included "yes" or "no"' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present \[from 1 (minor physical damage) to 5 (death), with 5 being most severe\]. C-SSRS SI items involved (a) wish to be dead, (b) non-specific active suicidal thoughts, (c) active SI with any methods (not plan) without intent to act, (d) active SI with some intent to act, without specific plan and (e) active SI with specific plan and intent. C-SSRS SB items involved (a) actual attempt, (b) engaged in non-suicidal self-injurious behavior, (c) interrupted attempt, (d) aborted attempt, (e) preparatory acts or behavior, (f) suicidal behavior. Only categories with data are reported.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item at Any Visit Suicidal Ideation: Wish to be Dead: Pre-infusion	0 percentage of participants	4.0 percentage of participants
Stage 1: Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item at Any Visit Suicidal Ideation: Non-specific Active Suicidal Thoughts: Pre-infusion	4.0 percentage of participants	0 percentage of participants
Stage 1: Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item at Any Visit Suicidal Behavior: Actual Attempt: Pre-infusion	4.0 percentage of participants	4.0 percentage of participants

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion and 10 hours and 7-day follow-up post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

The C-SSRS scale consisted of baseline evaluation that assessed lifetime experience of participants with SI and SB and postbaseline evaluation that focused on suicidality since last study visit. C-SSRS included "yes" or "no"' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present \[from 1 (minor physical damage) to 5 (death), with 5 being most severe\]. C-SSRS SI items involved (a) wish to be dead, (b) non-specific active suicidal thoughts, (c) active SI with any methods (not plan) without intent to act, (d) active SI with some intent to act, without specific plan and (e) active SI with specific plan and intent. C-SSRS SB items involved (a) actual attempt, (b) engaged in non-suicidal self-injurious behavior, (c) interrupted attempt, (d) aborted attempt, (e) preparatory acts or behavior, (f) suicidal behavior.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item at Any Visit	0 percentage of participants	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine systolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline (CFB) in Vital Signs Parameter - Supine Systolic Blood Pressure Pre-infusion	121.6 millimeters of mercury (mmHg) Standard Deviation 11.58	120.2 millimeters of mercury (mmHg) Standard Deviation 15.47
Stage 1: Change From Baseline (CFB) in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 4 Hours	-2.5 millimeters of mercury (mmHg) Standard Deviation 10.84	4.0 millimeters of mercury (mmHg) Standard Deviation 11.71
Stage 1: Change From Baseline (CFB) in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 8 Hours	-3.9 millimeters of mercury (mmHg) Standard Deviation 11.64	3.5 millimeters of mercury (mmHg) Standard Deviation 10.24
Stage 1: Change From Baseline (CFB) in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 12 Hours	-1.6 millimeters of mercury (mmHg) Standard Deviation 10.44	7.6 millimeters of mercury (mmHg) Standard Deviation 10.14
Stage 1: Change From Baseline (CFB) in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 12-hour Follow-up	5.6 millimeters of mercury (mmHg) Standard Deviation 8.68	1.4 millimeters of mercury (mmHg) Standard Deviation 11.85

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine systolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure Pre-infusion	125.3 mmHg Standard Deviation 13.22	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 2 Hours	-12.1 mmHg Standard Deviation 14.95	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 4 Hours	-7.6 mmHg Standard Deviation 17.12	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 6 Hours	-7.9 mmHg Standard Deviation 14.01	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 8 Hours	-6.8 mmHg Standard Deviation 17.44	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 10 Hours	-2.9 mmHg Standard Deviation 13.48	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 12 Hours	4.0 mmHg Standard Deviation 13.22	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 14 Hours	3.1 mmHg Standard Deviation 18.44	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Systolic Blood Pressure CFB at 24 Hours	4.3 mmHg Standard Deviation 11.12	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine diastolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure Pre-infusion	74.3 mmHg Standard Deviation 8.90	75.0 mmHg Standard Deviation 11.24
Stage 1: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 4 Hours	-2.3 mmHg Standard Deviation 9.85	-0.6 mmHg Standard Deviation 6.10
Stage 1: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 8 Hours	-2.0 mmHg Standard Deviation 6.79	-0.7 mmHg Standard Deviation 8.27
Stage 1: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 12 Hours	0.4 mmHg Standard Deviation 8.33	1.2 mmHg Standard Deviation 9.69
Stage 1: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 12-hour Follow-up	2.0 mmHg Standard Deviation 8.17	0.8 mmHg Standard Deviation 9.68

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine diastolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure Pre-infusion	75.5 mmHg Standard Deviation 7.63	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 2 Hours	-7.9 mmHg Standard Deviation 8.59	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 4 Hours	-6.4 mmHg Standard Deviation 10.20	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 6 Hours	-4.6 mmHg Standard Deviation 9.70	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 8 Hours	-8.8 mmHg Standard Deviation 10.17	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 10 Hours	-2.4 mmHg Standard Deviation 9.52	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 12 Hours	0.3 mmHg Standard Deviation 8.80	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 14 Hours	-2.2 mmHg Standard Deviation 9.03	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Diastolic Blood Pressure CFB at 24 Hours	-0.3 mmHg Standard Deviation 8.99	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Vital Signs Parameter - Supine Heart Rate Pre-infusion	66.0 beats per minute (bpm) Standard Deviation 9.70	69.0 beats per minute (bpm) Standard Deviation 12.99
Stage 1: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 4 Hours	-1.4 beats per minute (bpm) Standard Deviation 7.52	-2.1 beats per minute (bpm) Standard Deviation 10.39
Stage 1: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 8 Hours	2.0 beats per minute (bpm) Standard Deviation 6.37	1.3 beats per minute (bpm) Standard Deviation 14.85
Stage 1: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 12 Hours	5.0 beats per minute (bpm) Standard Deviation 8.67	2.1 beats per minute (bpm) Standard Deviation 11.23
Stage 1: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 12-hour Follow-up	2.9 beats per minute (bpm) Standard Deviation 9.17	-2.3 beats per minute (bpm) Standard Deviation 8.96

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in supine heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate Pre-infusion	69.5 bpm Standard Deviation 10.96	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 2 Hours	0.7 bpm Standard Deviation 10.18	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 4 Hours	-3.3 bpm Standard Deviation 7.22	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 6 Hours	-3.3 bpm Standard Deviation 10.30	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 8 Hours	-1.5 bpm Standard Deviation 9.00	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 10 Hours	-1.5 bpm Standard Deviation 9.10	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 12 Hours	-2.1 bpm Standard Deviation 8.55	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 14 Hours	3.9 bpm Standard Deviation 10.29	—
Stage 2: Change From Baseline in Vital Signs Parameter - Supine Heart Rate CFB at 24 Hours	2.6 bpm Standard Deviation 8.70	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1 .

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing systolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure Pre-infusion	118.0 mmHg Standard Deviation 17.27	119.1 mmHg Standard Deviation 15.00
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 4 Hours	-2.2 mmHg Standard Deviation 10.70	1.7 mmHg Standard Deviation 12.48
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 8 Hours	-2.7 mmHg Standard Deviation 13.23	1.0 mmHg Standard Deviation 12.87
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 12 Hours	2.0 mmHg Standard Deviation 12.65	7.8 mmHg Standard Deviation 11.48
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 12-hour Follow-up	5.0 mmHg Standard Deviation 15.82	1.7 mmHg Standard Deviation 10.76

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing systolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure Pre-infusion	120.1 mmHg Standard Deviation 13.05	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 2 Hours	-5.5 mmHg Standard Deviation 15.98	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 4 Hours	-5.9 mmHg Standard Deviation 13.87	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 6 Hours	-1.0 mmHg Standard Deviation 16.84	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 8 Hours	-2.9 mmHg Standard Deviation 14.22	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 10 Hours	-0.9 mmHg Standard Deviation 16.49	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 12 Hours	10.2 mmHg Standard Deviation 17.28	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 14 Hours	11.1 mmHg Standard Deviation 18.98	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Systolic Blood Pressure CFB at 24 Hours	2.9 mmHg Standard Deviation 9.30	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing diastolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure Pre-infusion	76.2 mmHg Standard Deviation 10.20	78.9 mmHg Standard Deviation 11.84
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 4 Hours	-1.2 mmHg Standard Deviation 8.86	-3.1 mmHg Standard Deviation 6.81
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 8 Hours	-2.1 mmHg Standard Deviation 9.03	-2.6 mmHg Standard Deviation 7.34
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 12 Hours	1.0 mmHg Standard Deviation 9.53	0.6 mmHg Standard Deviation 9.31
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 12-hour Follow-up	2.7 mmHg Standard Deviation 9.85	0.9 mmHg Standard Deviation 6.65

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing diastolic blood pressure is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure Pre-infusion	78.9 mmHg Standard Deviation 8.81	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 2 Hours	-5.6 mmHg Standard Deviation 7.17	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 4 Hours	-4.5 mmHg Standard Deviation 8.43	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 6 Hours	-4.1 mmHg Standard Deviation 6.66	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 8 Hours	-4.7 mmHg Standard Deviation 6.03	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 10 Hours	-4.3 mmHg Standard Deviation 9.21	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 12 Hours	-1.3 mmHg Standard Deviation 8.30	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 14 Hours	-0.6 mmHg Standard Deviation 8.73	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Diastolic Blood Pressure CFB at 24 Hours	-1.5 mmHg Standard Deviation 6.52	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Heart Rate Pre-infusion	72.0 bpm Standard Deviation 9.66	75.6 bpm Standard Deviation 13.70
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 4 Hours	0.0 bpm Standard Deviation 7.13	-1.0 bpm Standard Deviation 9.17
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 8 Hours	3.0 bpm Standard Deviation 7.55	-0.0 bpm Standard Deviation 10.22
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 12 Hours	5.4 bpm Standard Deviation 11.84	3.4 bpm Standard Deviation 8.23
Stage 1: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 12-hour Follow-up	3.8 bpm Standard Deviation 8.15	-1.5 bpm Standard Deviation 9.38

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in standing heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate Pre-infusion	74.6 bpm Standard Deviation 10.12	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 2 Hours	1.2 bpm Standard Deviation 9.25	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 4 Hours	0.7 bpm Standard Deviation 7.69	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 6 Hours	-1.2 bpm Standard Deviation 7.06	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 8 Hours	2.6 bpm Standard Deviation 11.09	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 10 Hours	3.5 bpm Standard Deviation 8.53	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 12 Hours	-1.5 bpm Standard Deviation 6.26	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 14 Hours	2.3 bpm Standard Deviation 10.02	—
Stage 2: Change From Baseline in Vital Signs Parameter - Standing Heart Rate CFB at 24 Hours	4.6 bpm Standard Deviation 11.17	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in temperature is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Vital Signs Parameter - Temperature Pre-infusion	36.62 degree Celsius Standard Deviation 0.14	36.58 degree Celsius Standard Deviation 0.16
Stage 1: Change From Baseline in Vital Signs Parameter - Temperature CFB at 4 Hours	-0.03 degree Celsius Standard Deviation 0.22	0.05 degree Celsius Standard Deviation 0.25
Stage 1: Change From Baseline in Vital Signs Parameter - Temperature CFB at 8 Hours	-0.04 degree Celsius Standard Deviation 0.16	0.06 degree Celsius Standard Deviation 0.28
Stage 1: Change From Baseline in Vital Signs Parameter - Temperature CFB at 12 Hours	-0.02 degree Celsius Standard Deviation 0.20	0.04 degree Celsius Standard Deviation 0.23
Stage 1: Change From Baseline in Vital Signs Parameter - Temperature CFB at 12-hour Follow-up	-0.01 degree Celsius Standard Deviation 0.22	-0.00 degree Celsius Standard Deviation 0.23

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in temperature is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in Vital Signs Parameter - Temperature Pre-infusion	36.64 degree Celsius Standard Deviation 0.15	—
Stage 2: Change From Baseline in Vital Signs Parameter - Temperature CFB at 2 Hours	-0.01 degree Celsius Standard Deviation 0.25	—
Stage 2: Change From Baseline in Vital Signs Parameter - Temperature CFB at 4 Hours	-0.06 degree Celsius Standard Deviation 0.20	—
Stage 2: Change From Baseline in Vital Signs Parameter - Temperature CFB at 6 Hours	0.01 degree Celsius Standard Deviation 0.18	—
Stage 2: Change From Baseline in Vital Signs Parameter - Temperature CFB at 8 Hours	-0.02 degree Celsius Standard Deviation 0.23	—
Stage 2: Change From Baseline in Vital Signs Parameter - Temperature CFB at 10 Hours	0.02 degree Celsius Standard Deviation 0.20	—
Stage 2: Change From Baseline in Vital Signs Parameter - Temperature CFB at 12 Hours	-0.01 degree Celsius Standard Deviation 0.40	—
Stage 2: Change From Baseline in Vital Signs Parameter - Temperature CFB at 14 Hours	0.02 degree Celsius Standard Deviation 0.21	—
Stage 2: Change From Baseline in Vital Signs Parameter - Temperature CFB at 24 Hours	-0.01 degree Celsius Standard Deviation 0.29	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in respiratory rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Vital Signs Parameter - Respiratory Rate Pre-infusion	16.0 breaths per minute (breaths/min) Standard Deviation 1.53	16.3 breaths per minute (breaths/min) Standard Deviation 1.46
Stage 1: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 4 Hours	0.4 breaths per minute (breaths/min) Standard Deviation 2.55	-0.2 breaths per minute (breaths/min) Standard Deviation 1.52
Stage 1: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 8 Hours	0.7 breaths per minute (breaths/min) Standard Deviation 2.43	0.3 breaths per minute (breaths/min) Standard Deviation 2.30
Stage 1: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 12 Hours	1.0 breaths per minute (breaths/min) Standard Deviation 2.30	0.4 breaths per minute (breaths/min) Standard Deviation 2.04
Stage 1: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 12-hour Follow-up	0.4 breaths per minute (breaths/min) Standard Deviation 1.70	0.2 breaths per minute (breaths/min) Standard Deviation 1.31

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 2, 4, 6, 8, 10, 12, 14 and 24 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Overall number of participants analyzed = Number of participants analyzed in this outcome measure. Number analyzed = Number of participants with data available at the specific time point.

Vital signs included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate, standing systolic blood pressure, standing diastolic blood pressure, standing heart rate, temperature, and respiratory rate. CFB in respiratory rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 12 Hours	0.5 breaths/min Standard Deviation 2.13	—
Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate Pre-infusion	16.9 breaths/min Standard Deviation 1.75	—
Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 2 Hours	-0.5 breaths/min Standard Deviation 1.81	—
Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 4 Hours	-0.4 breaths/min Standard Deviation 2.22	—
Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 6 Hours	-0.9 breaths/min Standard Deviation 2.31	—
Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 8 Hours	-0.4 breaths/min Standard Deviation 1.82	—
Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 10 Hours	0.3 breaths/min Standard Deviation 1.24	—
Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 14 Hours	0.1 breaths/min Standard Deviation 2.33	—
Stage 2: Change From Baseline in Vital Signs Parameter - Respiratory Rate CFB at 24 Hours	-0.5 breaths/min Standard Deviation 2.00	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in alanine aminotransferase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Alanine Aminotransferase Levels Pre-infusion	22.0 units per liter (u/L) Standard Deviation 12.15	23.3 units per liter (u/L) Standard Deviation 14.67
Stage 1: Change From Baseline in Serum Chemistry Parameter - Alanine Aminotransferase Levels CFB at 12-hour Follow-up	-1.4 units per liter (u/L) Standard Deviation 4.05	-2.7 units per liter (u/L) Standard Deviation 5.69

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for alanine aminotransferase levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Alanine Aminotransferase Levels Any Day in Screening Period (Day -7 up to Day -1)	23.1 u/L Standard Deviation 11.81	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Alanine Aminotransferase Levels Any Day in 7-day Follow-up	23.6 u/L Standard Deviation 13.06	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in aspartate aminotransferase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Aspartate Aminotransferase Levels Pre-infusion	19.2 u/L Standard Deviation 6.31	19.0 u/L Standard Deviation 5.81
Stage 1: Change From Baseline in Serum Chemistry Parameter - Aspartate Aminotransferase Levels CFB at 12-hour Follow-up	-0.7 u/L Standard Deviation 3.92	-0.0 u/L Standard Deviation 4.32

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for aspartate aminotransferase levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Aspartate Aminotransferase Levels Any Day in Screening Period (Day -7 up to Day -1)	15.8 u/L Standard Deviation 4.82	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Aspartate Aminotransferase Levels Any Day in 7-day Follow-up	15.6 u/L Standard Deviation 5.66	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in gamma glutamyl transferase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Gamma Glutamyl Transferase Levels Pre-infusion	27.0 u/L Standard Deviation 24.32	25.2 u/L Standard Deviation 21.40
Stage 1: Change From Baseline in Serum Chemistry Parameter - Gamma Glutamyl Transferase Levels CFB at 12-hour Follow-up	0.0 u/L Standard Deviation 4.16	1.2 u/L Standard Deviation 2.94

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for gamma glutamyl transferase levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Gamma Glutamyl Transferase Levels Any Day in Screening Period (Day -7 up to Day -1)	26.8 u/L Standard Deviation 21.72	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Gamma Glutamyl Transferase Levels Any Day in 7-day Follow-up	28.3 u/L Standard Deviation 19.65	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in sodium levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Sodium Levels Pre-infusion	140.4 millimoles per liter (mmol/L) Standard Deviation 2.38	140.2 millimoles per liter (mmol/L) Standard Deviation 2.35
Stage 1: Change From Baseline in Serum Chemistry Parameter - Sodium Levels CFB at 12-hour Follow-up	-0.2 millimoles per liter (mmol/L) Standard Deviation 2.19	-0.6 millimoles per liter (mmol/L) Standard Deviation 3.28

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for sodium levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Sodium Levels Any Day in Screening Period (Day -7 up to Day -1)	139.4 mmol/L Standard Deviation 2.18	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Sodium Levels Any Day in 7-day Follow-up	139.4 mmol/L Standard Deviation 1.91	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in potassium levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Potassium Levels Pre-infusion	4.18 mmol/L Standard Deviation 0.273	4.17 mmol/L Standard Deviation 0.301
Stage 1: Change From Baseline in Serum Chemistry Parameter - Potassium Levels CFB at 12-hour Follow-up	-0.00 mmol/L Standard Deviation 0.301	0.10 mmol/L Standard Deviation 0.335

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for potassium levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Potassium Levels Any Day in Screening Period (Day -7 up to Day -1)	4.36 mmol/L Standard Deviation 0.232	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Potassium Levels Any Day in 7-day Follow-up	4.42 mmol/L Standard Deviation 0.268	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in calcium levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Calcium Levels Pre-infusion	9.07 milligrams per deciliter (mg/dL) Standard Deviation 0.366	9.08 milligrams per deciliter (mg/dL) Standard Deviation 0.376
Stage 1: Change From Baseline in Serum Chemistry Parameter - Calcium Levels CFB at 12-hour Follow-up	-0.11 milligrams per deciliter (mg/dL) Standard Deviation 0.492	-0.12 milligrams per deciliter (mg/dL) Standard Deviation 0.393

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for calcium levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Calcium Levels Any Day in Screening Period (Day -7 up to Day -1)	9.19 mg/dL Standard Deviation 0.302	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Calcium Levels Any Day in 7-day Follow-up	9.12 mg/dL Standard Deviation 0.268	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in chloride levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Chloride Levels Pre-infusion	106.4 mmol/L Standard Deviation 3.34	105.8 mmol/L Standard Deviation 3.00
Stage 1: Change From Baseline in Serum Chemistry Parameter - Chloride Levels CFB at 12-hour Follow-up	-0.2 mmol/L Standard Deviation 2.54	-0.2 mmol/L Standard Deviation 2.00

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for chloride levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Chloride Levels Any Day in Screening Period (Day -7 up to Day -1)	103.8 mmol/L Standard Deviation 2.79	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Chloride Levels Any Day in 7-day Follow-up	104.2 mmol/L Standard Deviation 2.54	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in bicarbonate levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Bicarbonate Levels Pre-infusion	25.6 mmol/L Standard Deviation 3.47	25.6 mmol/L Standard Deviation 2.87
Stage 1: Change From Baseline in Serum Chemistry Parameter - Bicarbonate Levels CFB at 12-hour Follow-up	-0.4 mmol/L Standard Deviation 2.71	-0.7 mmol/L Standard Deviation 2.95

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for bicarbonate levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Bicarbonate Levels Any Day in Screening Period (Day -7 up to Day -1)	26.6 mmol/L Standard Deviation 3.91	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Bicarbonate Levels Any Day in 7-day Follow-up	26.3 mmol/L Standard Deviation 3.60	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in protein levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Protein Levels Pre-infusion	6.70 grams per deciliter (g/dL) Standard Deviation 0.452	6.66 grams per deciliter (g/dL) Standard Deviation 0.390
Stage 1: Change From Baseline in Serum Chemistry Parameter - Protein Levels CFB at 12-hour Follow-up	-0.08 grams per deciliter (g/dL) Standard Deviation 0.456	0.05 grams per deciliter (g/dL) Standard Deviation 0.366

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for protein levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Protein Levels Any Day in Screening Period (Day -7 up to Day -1)	7.05 g/dL Standard Deviation 0.403	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Protein Levels Any Day in 7-day Follow-up	6.80 g/dL Standard Deviation 0.417	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in glucose levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Glucose Levels Pre-infusion	108.0 mg/dL Standard Deviation 34.29	95.4 mg/dL Standard Deviation 17.21
Stage 1: Change From Baseline in Serum Chemistry Parameter - Glucose Levels CFB at 12-hour Follow-up	0.0 mg/dL Standard Deviation 38.89	19.6 mg/dL Standard Deviation 52.94

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for glucose levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Glucose Levels Any Day in Screening Period (Day -7 up to Day -1)	108.1 mg/dL Standard Deviation 60.88	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Glucose Levels Any Day in 7-day Follow-up	112.8 mg/dL Standard Deviation 71.74	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure. Number analyzed = Number of participants with data available at the specific time point.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in lactate dehydrogenase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=15 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=14 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Lactate Dehydrogenase Levels Pre-infusion	167.9 u/L Standard Deviation 32.75	153.1 u/L Standard Deviation 29.87
Stage 1: Change From Baseline in Serum Chemistry Parameter - Lactate Dehydrogenase Levels CFB at 12-hour Follow-up	-16.6 u/L Standard Deviation 15.59	-0.8 u/L Standard Deviation 17.57

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for lactate dehydrogenase levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Lactate Dehydrogenase Levels Any Day in Screening Period (Day -7 up to Day -1)	162.9 u/L Standard Deviation 39.06	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Lactate Dehydrogenase Levels Any Day in 7-day Follow-up	168.8 u/L Standard Deviation 40.97	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure. Number analyzed = Number of participants with data available at the specific time point.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in cholesterol levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=23 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=23 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Cholesterol Levels Pre-infusion	183.0 mg/dL Standard Deviation 32.77	183.4 mg/dL Standard Deviation 24.63
Stage 1: Change From Baseline in Serum Chemistry Parameter - Cholesterol Levels CFB at 12-hour Follow-up	0.4 mg/dL Standard Deviation 14.01	2.1 mg/dL Standard Deviation 20.84

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for cholesterol levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Cholesterol Level Any Day in Screening Period (Day -7 up to Day -1)	194.6 mg/dL Standard Deviation 39.64	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Cholesterol Level Any Day in 7-day Follow-up	179.7 mg/dL Standard Deviation 33.94	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure. Number analyzed = Number of participants with data available at the specific time point.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in triglyceride levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=23 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=23 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Triglyceride Levels Pre-infusion	166.1 mg/dL Standard Deviation 93.42	168.4 mg/dL Standard Deviation 77.72
Stage 1: Change From Baseline in Serum Chemistry Parameter - Triglyceride Levels CFB at 12-hour Follow-up	-19.1 mg/dL Standard Deviation 67.47	-25.1 mg/dL Standard Deviation 45.41

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for triglyceride levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Triglyceride Levels Any Day in Screening Period (Day -7 up to Day -1)	162.4 mg/dL Standard Deviation 63.59	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Triglyceride Levels Any Day in 7-day Follow-up	163.4 mg/dL Standard Deviation 69.94	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in albumin levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Albumin Levels Pre-infusion	3.94 g/dL Standard Deviation 0.260	3.95 g/dL Standard Deviation 0.315
Stage 1: Change From Baseline in Serum Chemistry Parameter - Albumin Levels CFB at 12-hour Follow-up	-0.06 g/dL Standard Deviation 0.314	-0.01 g/dL Standard Deviation 0.276

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for albumin levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Albumin Levels Any Day in Screening Period (Day -7 up to Day -1)	4.03 g/dL Standard Deviation 0.331	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Albumin Levels Any Day in 7-day Follow-up	3.92 g/dL Standard Deviation 0.299	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in bilirubin levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Bilirubin Levels Pre-infusion	0.44 mg/dL Standard Deviation 0.231	0.47 mg/dL Standard Deviation 0.313
Stage 1: Change From Baseline in Serum Chemistry Parameter - Bilirubin Levels CFB at 12-hour Follow-up	0.04 mg/dL Standard Deviation 0.144	0.09 mg/dL Standard Deviation 0.127

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for bilirubin levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Bilirubin Levels Any Day in Screening Period (Day -7 up to Day -1)	0.58 mg/dL Standard Deviation 0.354	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Bilirubin Levels Any Day in 7-day Follow-up	0.57 mg/dL Standard Deviation 0.463	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in creatinine levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Creatinine Levels Pre-infusion	0.940 mg/dL Standard Deviation 0.2480	0.951 mg/dL Standard Deviation 0.2912
Stage 1: Change From Baseline in Serum Chemistry Parameter - Creatinine Levels CFB at 12-hour Follow-up	-0.07 mg/dL Standard Deviation 0.104	-0.09 mg/dL Standard Deviation 0.128

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for creatinine levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Creatinine Levels Any Day in Screening Period (Day -7 up to Day -1)	0.872 mg/dL Standard Deviation 0.2302	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Creatinine Levels Any Day in 7-day Follow-up	0.912 mg/dL Standard Deviation 0.2234	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in blood urea nitrogen levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Blood Urea Nitrogen Levels Pre-infusion	18.1 mg/dL Standard Deviation 4.60	17.9 mg/dL Standard Deviation 5.73
Stage 1: Change From Baseline in Serum Chemistry Parameter - Blood Urea Nitrogen Levels CFB at 12-hour Follow-up	-0.4 mg/dL Standard Deviation 4.36	-0.3 mg/dL Standard Deviation 3.08

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for blood urea nitrogen levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Blood Urea Nitrogen Levels Any Day in Screening Period (Day -7 up to Day -1)	17.3 mg/dL Standard Deviation 4.31	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Blood Urea Nitrogen Levels Any Day in 7-day Follow-up	16.6 mg/dL Standard Deviation 3.37	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in alkaline phosphatase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=23 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=23 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Alkaline Phosphatase Levels Pre-infusion	69.1 u/L Standard Deviation 13.97	67.1 u/L Standard Deviation 13.58
Stage 1: Change From Baseline in Serum Chemistry Parameter - Alkaline Phosphatase Levels CFB at 12-hour Follow-up	-2.4 u/L Standard Deviation 5.37	-0.4 u/L Standard Deviation 6.83

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for alkaline phosphatase levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Alkaline Phosphatase Levels Any Day in Screening Period (Day -7 up to Day -1)	71.1 u/L Standard Deviation 13.99	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Alkaline Phosphatase Levels Any Day in 7-day Follow-up	71.4 u/L Standard Deviation 14.33	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in creatinine kinase levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=23 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=21 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Creatine Kinase Levels Pre-infusion	100.5 u/L Standard Deviation 71.25	124.0 u/L Standard Deviation 188.98
Stage 1: Change From Baseline in Serum Chemistry Parameter - Creatine Kinase Levels CFB at 12-hour Follow-up	-20.6 u/L Standard Deviation 25.57	-36.2 u/L Standard Deviation 90.71

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for creatinine kinase levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Creatine Kinase Levels Any Day in Screening Period (Day -7 up to Day -1)	83.9 u/L Standard Deviation 32.51	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Creatine Kinase Levels Any Day in 7-day Follow-up	85.9 u/L Standard Deviation 44.45	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Number analyzed = Number of participants with data available at the specific time point.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in phosphate levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Phosphate Levels Pre-infusion	3.58 mg/dL Standard Deviation 0.468	3.52 mg/dL Standard Deviation 0.551
Stage 1: Change From Baseline in Serum Chemistry Parameter - Phosphate Levels CFB at 12-hour Follow-up	-0.16 mg/dL Standard Deviation 0.481	-0.17 mg/dL Standard Deviation 0.581

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for phosphate levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Phosphate Levels Any Day in Screening Period (Day -7 up to Day -1)	3.36 mg/dL Standard Deviation 0.436	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Phosphate Levels Any Day in 7-day Follow-up	3.23 mg/dL Standard Deviation 0.461	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. CFB in urate levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=23 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=23 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Serum Chemistry Parameter - Urate Levels Pre-infusion	4.53 mg/dL Standard Deviation 1.249	4.71 mg/dL Standard Deviation 1.366
Stage 1: Change From Baseline in Serum Chemistry Parameter - Urate Levels CFB at 12-hour Follow-up	0.05 mg/dL Standard Deviation 0.532	-0.04 mg/dL Standard Deviation 0.317

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, sodium, potassium, calcium, chloride, bicarbonate, protein, glucose, lactate dehydrogenase, cholesterol, triglycerides, albumin, bilirubin, creatinine, blood urea nitrogen, alkaline phosphatase, creatinine kinase, phosphate, and urate. Absolute values for urate levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Serum Chemistry Parameter - Urate Levels Any Day in Screening Period (Day -7 up to Day -1)	4.66 mg/dL Standard Deviation 1.169	—
Stage 2: Absolute Values of Serum Chemistry Parameter - Urate Levels Any Day in 7-day Follow-up	4.84 mg/dL Standard Deviation 1.183	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in hemoglobin levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Hemoglobin Levels Pre-infusion	13.56 g/dL Standard Deviation 1.276	13.63 g/dL Standard Deviation 1.179
Stage 1: Change From Baseline in Hematology Parameter - Hemoglobin Levels CFB at 12-hours Follow-up	0.34 g/dL Standard Deviation 0.733	0.28 g/dL Standard Deviation 0.768

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for hemoglobin levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Hemoglobin Levels Any Day in Screening Period (Day -7 up to Day -1)	14.74 g/dL Standard Deviation 1.419	—
Stage 2: Absolute Values of Hematology Parameter - Hemoglobin Levels Any Day in 7-day Follow-up	14.11 g/dL Standard Deviation 1.684	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in hematocrit levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Hematocrit Levels Pre-infusion	40.66 percentage of cells Standard Deviation 3.463	40.97 percentage of cells Standard Deviation 3.453
Stage 1: Change From Baseline in Hematology Parameter - Hematocrit Levels CFB at 12-hours Follow-up	1.02 percentage of cells Standard Deviation 2.013	0.67 percentage of cells Standard Deviation 2.494

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for hematocrit levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Hematocrit Levels Any Day in Screening Period (Day -7 up to Day -1)	45.04 percentage of cells Standard Deviation 4.230	—
Stage 2: Absolute Values of Hematology Parameter - Hematocrit Levels Any Day in 7-day Follow-up	43.28 percentage of cells Standard Deviation 5.128	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in platelet levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Platelet Levels Pre-infusion	212.5 10^3 cells per microliter(10^3 cells/μL) Standard Deviation 40.56	218.8 10^3 cells per microliter(10^3 cells/μL) Standard Deviation 48.31
Stage 1: Change From Baseline in Hematology Parameter - Platelet Levels CFB at 12-hours Follow-up	-11.7 10^3 cells per microliter(10^3 cells/μL) Standard Deviation 45.02	-7.1 10^3 cells per microliter(10^3 cells/μL) Standard Deviation 37.11

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for platelet levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Platelet Levels Any Day in Screening Period (Day -7 up to Day -1)	233.8 10^3 cells/μL Standard Deviation 48.03	—
Stage 2: Absolute Values of Hematology Parameter - Platelet Levels Any Day in 7-day Follow-up	230.5 10^3 cells/μL Standard Deviation 45.93	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in erythrocyte levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Erythrocyte Levels Pre-infusion	4.437 10^6 cells per microliter(10^6 cells/μL) Standard Deviation 0.4032	4.474 10^6 cells per microliter(10^6 cells/μL) Standard Deviation 0.4119
Stage 1: Change From Baseline in Hematology Parameter - Erythrocyte Levels CFB at 12-hours Follow-up	0.09 10^6 cells per microliter(10^6 cells/μL) Standard Deviation 0.223	0.07 10^6 cells per microliter(10^6 cells/μL) Standard Deviation 0.271

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for erythrocyte levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Erythrocyte Levels Any Day in Screening Period (Day -7 up to Day -1)	4.925 10^6 cells/μL Standard Deviation 0.4173	—
Stage 2: Absolute Values of Hematology Parameter - Erythrocyte Levels Any Day in 7-day Follow-up	4.735 10^6 cells/μL Standard Deviation 0.5289	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in neutrophil levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=12 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=12 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Neutrophil Levels Pre-infusion	4.510 10^3 cells/μL Standard Deviation 1.2311	4.781 10^3 cells/μL Standard Deviation 1.6007
Stage 1: Change From Baseline in Hematology Parameter - Neutrophil Levels CFB at 12-hours Follow-up	-0.49 10^3 cells/μL Standard Deviation 0.941	-0.66 10^3 cells/μL Standard Deviation 1.053

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Overall number of participants analyzed = Number of participants analyzed in this outcome measure. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for neutrophil levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=11 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Neutrophil Levels Any Day in Screening Period (Day -7 up to Day -1)	4.049 10^3 cells/μL Standard Deviation 0.8958	—
Stage 2: Absolute Values of Hematology Parameter - Neutrophil Levels Any Day in 7-day Follow-up	4.176 10^3 cells/μL Standard Deviation 0.8065	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in basophil levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=13 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=13 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Basophil Levels Pre-infusion	25.4 cells per microliter (cells/μL) Standard Deviation 15.61	27.2 cells per microliter (cells/μL) Standard Deviation 20.45
Stage 1: Change From Baseline in Hematology Parameter - Basophil Levels CFB at 12-hours Follow-up	6.4 cells per microliter (cells/μL) Standard Deviation 17.06	-8.3 cells per microliter (cells/μL) Standard Deviation 21.83

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Overall number of participants analyzed = Number of participants analyzed in this outcome measure.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for basophil levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=6 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Basophil Levels Any Day in Screening Period (Day -7 up to Day -1)	35.3 cells/μL Standard Deviation 20.70	—
Stage 2: Absolute Values of Hematology Parameter - Basophil Levels Any Day in 7-day Follow-up	45.3 cells/μL Standard Deviation 47.64	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in eosinophil levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=13 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=13 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Eosinophil Levels Pre-infusion	158.8 cells/μL Standard Deviation 77.53	140.3 cells/μL Standard Deviation 109.72
Stage 1: Change From Baseline in Hematology Parameter - Eosinophil Levels CFB at 12-hours Follow-up	11.5 cells/μL Standard Deviation 45.21	42.5 cells/μL Standard Deviation 47.48

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Overall number of participants analyzed = Number of participants analyzed in this outcome measure.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for eosinophil levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=6 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Eosinophil Levels Any Day in Screening Period (Day -7 up to Day -1)	87.2 cells/μL Standard Deviation 40.49	—
Stage 2: Absolute Values of Hematology Parameter - Eosinophil Levels Any Day in 7-day Follow-up	99.8 cells/μL Standard Deviation 75.37	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in monocyte levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=13 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=13 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Monocyte Levels Pre-infusion	480.5 cells/μL Standard Deviation 264.68	462.8 cells/μL Standard Deviation 240.92
Stage 1: Change From Baseline in Hematology Parameter - Monocyte Levels CFB at 12-hours Follow-up	-22.9 cells/μL Standard Deviation 176.01	-40.3 cells/μL Standard Deviation 113.21

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Overall number of participants analyzed = Number of participants analyzed in this outcome measure.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for monocyte levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=6 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Monocyte Levels Any Day in Screening Period (Day -7 up to Day -1)	499.8 cells/μL Standard Deviation 190.38	—
Stage 2: Absolute Values of Hematology Parameter - Monocyte Levels Any Day in 7-day Follow-up	426.7 cells/μL Standard Deviation 133.11	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in lymphocyte levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=13 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=13 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Lymphocyte Levels Pre-infusion	1641.7 cells/μL Standard Deviation 423.63	1590.1 cells/μL Standard Deviation 427.61
Stage 1: Change From Baseline in Hematology Parameter - Lymphocyte Levels CFB at 12-hours Follow-up	176.5 cells/μL Standard Deviation 244.63	100.3 cells/μL Standard Deviation 310.99

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Overall number of participants analyzed = Number of participants analyzed in this outcome measure.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for lymphocyte levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=6 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Lymphocyte Levels Any Day in Screening Period (Day -7 up to Day -1)	2080.0 cells/μL Standard Deviation 908.52	—
Stage 2: Absolute Values of Hematology Parameter - Lymphocyte Levels Any Day in 7-day Follow-up	1871.8 cells/μL Standard Deviation 858.64	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in leukocyte levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Leukocyte Levels Pre-infusion	6.976 10^3 cells/μL Standard Deviation 1.9550	6.972 10^3 cells/μL Standard Deviation 2.1314
Stage 1: Change From Baseline in Hematology Parameter - Leukocyte Levels CFB at 12-hours Follow-up	-0.12 10^3 cells/μL Standard Deviation 1.090	-0.43 10^3 cells/μL Standard Deviation 0.927

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for leukocyte levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Leukocyte Levels Any Day in Screening Period (Day -7 up to Day -1)	6.928 10^3 cells/μL Standard Deviation 1.7603	—
Stage 2: Absolute Values of Hematology Parameter - Leukocyte Levels Any Day in 7-day Follow-up	6.688 10^3 cells/μL Standard Deviation 1.5791	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in erythrocytes mean corpuscular volume levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Volume Levels Pre-infusion	91.71 femtoliter (fL) Standard Deviation 3.774	91.72 femtoliter (fL) Standard Deviation 3.780
Stage 1: Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Volume Levels CFB at 12-hours Follow-up	0.30 femtoliter (fL) Standard Deviation 0.810	-0.03 femtoliter (fL) Standard Deviation 0.833

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for erythrocytes mean corpuscular volume levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Erythrocytes Mean Corpuscular Volume Levels Any Day in Screening Period (Day -7 up to Day -1)	91.59 fL Standard Deviation 5.264	—
Stage 2: Absolute Values of Hematology Parameter - Erythrocytes Mean Corpuscular Volume Levels Any Day in 7-day Follow-up	91.43 fL Standard Deviation 4.718	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 12-hour follow-up post-infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure. Number analyzed = Number of participants with data available at the specific time point.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. CFB in mean cell hemoglobin levels is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=13 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=13 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Hematology Parameter - Mean Cell Hemoglobin Levels Pre-infusion	30.58 picograms (pg) Standard Deviation 1.540	30.90 picograms (pg) Standard Deviation 1.760
Stage 1: Change From Baseline in Hematology Parameter - Mean Cell Hemoglobin Levels CFB at 12-hours Follow-up	0.18 picograms (pg) Standard Deviation 0.468	-0.30 picograms (pg) Standard Deviation 0.792

PRIMARY outcome

Timeframe: Stage 2: Any day in Screening period (Day -7 up to Day -1) and any day in 7-day follow up

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Overall number of participants analyzed = Number of participants analyzed in this outcome measure.

Hematology parameters included hemoglobin, hematocrit, platelets, erythrocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, leukocytes, erythrocytes mean corpuscular volume, and mean cell hemoglobin. Absolute values for mean cell hemoglobin levels are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=6 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Absolute Values of Hematology Parameter - Mean Cell Hemoglobin Any Day in Screening Period (Day -7 up to Day -1)	29.93 pg Standard Deviation 2.890	—
Stage 2: Absolute Values of Hematology Parameter - Mean Cell Hemoglobin Any Day in 7-day Follow-up	29.97 pg Standard Deviation 2.809	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8,12 hours during infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QT interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Electrocardiogram (ECG) Parameter - QT Interval Pre-infusion	392.0 milliseconds (msec) Interval 362.0 to 493.0	394.0 milliseconds (msec) Interval 359.0 to 462.0
Stage 1: Change From Baseline in Electrocardiogram (ECG) Parameter - QT Interval CFB at 4 Hours	3.0 milliseconds (msec) Interval -88.0 to 28.0	-2.0 milliseconds (msec) Interval -31.0 to 26.0
Stage 1: Change From Baseline in Electrocardiogram (ECG) Parameter - QT Interval CFB at 8 Hours	-8.0 milliseconds (msec) Interval -92.0 to 18.0	-10.0 milliseconds (msec) Interval -64.0 to 38.0
Stage 1: Change From Baseline in Electrocardiogram (ECG) Parameter - QT Interval CFB at 12 Hours	-12.0 milliseconds (msec) Interval -90.0 to 24.0	-14.0 milliseconds (msec) Interval -48.0 to 32.0

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QT interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in ECG Parameter - QT Interval Pre-infusion	376.0 msec Interval 368.0 to 422.0	—
Stage 2: Change From Baseline in ECG Parameter - QT Interval CFB at 10 Hours	-1.0 msec Interval -33.0 to 28.0	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8,12 hours during infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in PR interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in ECG Parameter - PR Interval Pre-infusion	168.0 msec Interval 108.0 to 214.0	170.0 msec Interval 116.0 to 262.0
Stage 1: Change From Baseline in ECG Parameter - PR Interval CFB at 4 Hours	0.0 msec Interval -168.0 to 46.0	-4.0 msec Interval -46.0 to 28.0
Stage 1: Change From Baseline in ECG Parameter - PR Interval CFB at 8 Hours	-3.0 msec Interval -18.0 to 54.0	-2.0 msec Interval -30.0 to 18.0
Stage 1: Change From Baseline in ECG Parameter - PR Interval CFB at 12 Hours	-4.0 msec Interval -158.0 to 74.0	-6.0 msec Interval -52.0 to 39.0

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in PR interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in ECG Parameter - PR Interval Pre-infusion	144.0 msec Interval 136.0 to 174.0	—
Stage 2: Change From Baseline in ECG Parameter - PR Interval CFB at 10 Hours	2.5 msec Interval -6.0 to 43.0	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QRS duration is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in ECG Parameter - QRS Duration Pre-infusion	86.0 msec Interval 72.0 to 236.0	85.0 msec Interval 72.0 to 122.0
Stage 1: Change From Baseline in ECG Parameter - QRS Duration CFB at 4 Hours	0.0 msec Interval -162.0 to 15.0	0.0 msec Interval -10.0 to 6.0
Stage 1: Change From Baseline in ECG Parameter - QRS Duration CFB at 8 Hours	0.0 msec Interval -166.0 to 9.0	0.0 msec Interval -8.0 to 13.0
Stage 1: Change From Baseline in ECG Parameter - QRS Duration CFB at 12 Hours	0.0 msec Interval -162.0 to 22.0	0.0 msec Interval -13.0 to 15.0

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QRS duration is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in ECG Parameter - QRS Duration Pre-infusion	90.0 msec Interval 74.0 to 122.0	—
Stage 2: Change From Baseline in ECG Parameter - QRS Duration CFB at 10 Hours	0.0 msec Interval -6.0 to 15.0	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QTcB interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in ECG Parameter - QTcB Interval Pre-infusion	412.0 msec Interval 380.0 to 524.0	413.0 msec Interval 383.0 to 455.0
Stage 1: Change From Baseline in ECG Parameter - QTcB Interval CFB at 4 Hours	-1.0 msec Interval -111.0 to 18.0	1.0 msec Interval -27.0 to 20.0
Stage 1: Change From Baseline in ECG Parameter - QTcB Interval CFB at 8 Hours	5.0 msec Interval -115.0 to 28.0	0.0 msec Interval -25.0 to 20.0
Stage 1: Change From Baseline in ECG Parameter - QTcB Interval CFB at 12 Hours	4.0 msec Interval -108.0 to 78.0	-1.0 msec Interval -18.0 to 24.0

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QTcB interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in ECG Parameter - QTcB Interval Pre-infusion	421.0 msec Interval 391.0 to 446.0	—
Stage 2: Change From Baseline in ECG Parameter - QTcB Interval CFB at 10 Hours	1.5 msec Interval -22.0 to 25.0	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QTcF interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in ECG Parameter - QTcF Interval Pre-infusion	404.0 msec Interval 380.0 to 502.0	404.0 msec Interval 389.0 to 451.0
Stage 1: Change From Baseline in ECG Parameter - QTcF Interval CFB at 4 Hours	2.0 msec Interval -103.0 to 20.0	0.0 msec Interval -24.0 to 18.0
Stage 1: Change From Baseline in ECG Parameter - QTcF Interval CFB at 8 Hours	1.0 msec Interval -108.0 to 17.0	-3.0 msec Interval -17.0 to 20.0
Stage 1: Change From Baseline in ECG Parameter - QTcF Interval CFB at 12 Hours	1.0 msec Interval -102.0 to 59.0	-7.0 msec Interval -17.0 to 23.0

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in QTcF interval is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in ECG Parameter - QTcF Interval Pre-infusion	406.0 msec Interval 386.0 to 438.0	—
Stage 2: Change From Baseline in ECG Parameter - QTcF Interval CFB at 10 Hours	2.5 msec Interval -15.0 to 26.0	—

PRIMARY outcome

Timeframe: Day 1 of Stage 1 (Treatment Period 1) or on Day 10 of Stage 1 (Treatment Period 2): Pre-infusion (Baseline) and 4, 8, 12 hours during infusion

Population: Safety population included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in ECG Parameter - Heart Rate Pre-infusion	65.0 bpm Standard Deviation 9.70	65.0 bpm Standard Deviation 9.09
Stage 1: Change From Baseline in ECG Parameter - Heart Rate CFB at 4 Hours	-1.9 bpm Standard Deviation 6.36	0.2 bpm Standard Deviation 4.33
Stage 1: Change From Baseline in ECG Parameter - Heart Rate CFB at 8 Hours	3.3 bpm Standard Deviation 6.46	3.0 bpm Standard Deviation 9.05
Stage 1: Change From Baseline in ECG Parameter - Heart Rate CFB at 12 Hours	5.5 bpm Standard Deviation 7.35	4.6 bpm Standard Deviation 7.34

PRIMARY outcome

Timeframe: Stage 2 Day 1: Pre-infusion (Baseline) and 10 hours post-infusion

Population: Participants from safety population, which included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

ECG parameters included QT interval, PR interval, QRS duration, QTcB interval, QTcF interval, and heart rate. CFB in heart rate is reported in this outcome measure. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in ECG Parameter - Heart Rate Pre-infusion	72.0 bpm Standard Deviation 8.27	—
Stage 2: Change From Baseline in ECG Parameter - Heart Rate CFB at 10 Hours	-0.4 bpm Standard Deviation 5.97	—

SECONDARY outcome

Timeframe: Stage 1 Days 1 and 10: Pre-infusion (Baseline) and 2, 4, 6, 8, 10 and 12 hours and 12-hour follow-up post-infusion

Population: Efficacy population was defined as all participants in the safety population who completed ≥12 hours of infusion and had efficacy evaluations through the 12-hour visits in both Treatment Periods 1 and 2 of Stage 1. Number analyzed = Number of participants with data available at the specific time point.

Accelerometer total score response was defined as ≥30% decrease from baseline to each time point in accelerometer total score. Accelerometer total score is sum of forward outstretched postural tremor, lateral wing-beating postural tremor, and kinetic tremor scores across both sides of the body (i.e., right and left). Accelerometer was used for transducer measurement of tremor amplitude. Participants wore wireless ring motion sensor. It measured linear acceleration and angular velocity (i.e., kinesia score). Information from motion sensor data was correlated to symptoms of tremor. Kinesia (accelerometer) scores ranged from 0 to 4 in 0.5 step increments. The total score ranges from 0 to 24, higher scores indicating more severe tremors. Negative change from baseline indicated decrease in tremor. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Accelerometer Total Score Response Pre-infusion	7.13 score on a scale Standard Deviation 3.902	7.41 score on a scale Standard Deviation 4.137
Stage 1: Change From Baseline in Accelerometer Total Score Response CFB at 2 Hours	-0.96 score on a scale Standard Deviation 1.373	-1.05 score on a scale Standard Deviation 1.563
Stage 1: Change From Baseline in Accelerometer Total Score Response CFB at 4 Hours	-0.83 score on a scale Standard Deviation 1.876	-0.74 score on a scale Standard Deviation 1.833
Stage 1: Change From Baseline in Accelerometer Total Score Response CFB at 6 Hours	-1.25 score on a scale Standard Deviation 1.943	-0.75 score on a scale Standard Deviation 1.186
Stage 1: Change From Baseline in Accelerometer Total Score Response CFB at 8 Hours	-0.93 score on a scale Standard Deviation 1.903	-1.03 score on a scale Standard Deviation 1.447
Stage 1: Change From Baseline in Accelerometer Total Score Response CFB at 10 Hours	-1.24 score on a scale Standard Deviation 1.814	-0.85 score on a scale Standard Deviation 1.713
Stage 1: Change From Baseline in Accelerometer Total Score Response CFB at 12 Hours	-1.39 score on a scale Standard Deviation 1.436	-0.91 score on a scale Standard Deviation 1.284
Stage 1: Change From Baseline in Accelerometer Total Score Response CFB at 12-hour Follow-up	0.05 score on a scale Standard Deviation 1.498	-0.21 score on a scale Standard Deviation 1.927

SECONDARY outcome

Timeframe: Stage 2 Day 1: Baseline and 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours

Population: Efficacy population was participants from safety population, who completed ≥12 hours of infusion and had efficacy evaluations through the 12-hour visits in both Treatment Periods 1 and 2, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

Accelerometer total score response was defined as ≥30% decrease from baseline to each time point in accelerometer total score. Accelerometer total score is sum of forward outstretched postural tremor, lateral wing beating postural tremor, and kinetic tremor scores across both sides of the body (i.e., right and left). Accelerometer was used for transducer measurement of tremor amplitude. Participants wore wireless ring motion sensor. It measured linear acceleration and angular velocity (i.e., kinesia score). Information from motion sensor data was correlated to symptoms of tremor. Kinesia (accelerometer) scores ranged from 0 to 4 in 0.5 step increments. The total score ranges from 0 to 24, higher scores indicating more severe tremors. Negative change from baseline indicated decrease in tremor. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in Accelerometer Total Score Response Baseline	6.96 score on a scale Standard Deviation 4.901	—
Stage 2: Change From Baseline in Accelerometer Total Score Response CFB at 2 Hours	-1.37 score on a scale Standard Deviation 2.202	—
Stage 2: Change From Baseline in Accelerometer Total Score Response CFB at 3 Hours	-1.25 score on a scale Standard Deviation 1.890	—
Stage 2: Change From Baseline in Accelerometer Total Score Response CFB at 4 Hours	-1.57 score on a scale Standard Deviation 2.186	—
Stage 2: Change From Baseline in Accelerometer Total Score Response CFB at 6 Hours	-1.44 score on a scale Standard Deviation 2.553	—
Stage 2: Change From Baseline in Accelerometer Total Score Response CFB at 8 Hours	-2.06 score on a scale Standard Deviation 2.942	—
Stage 2: Change From Baseline in Accelerometer Total Score Response CFB at 10 Hours	-1.16 score on a scale Standard Deviation 1.809	—
Stage 2: Change From Baseline in Accelerometer Total Score Response CFB at 12 Hours	-0.89 score on a scale Standard Deviation 1.845	—
Stage 2: Change From Baseline in Accelerometer Total Score Response CFB at 14 Hours	-0.35 score on a scale Standard Deviation 1.780	—
Stage 2: Change From Baseline in Accelerometer Total Score Response CFB at 24 Hours	0.18 score on a scale Standard Deviation 2.033	—

SECONDARY outcome

Timeframe: Stage 1 Days 1 and 10: Pre-infusion (Baseline) and 2, 4, 6, 8, 10 and 12 hours and 12-hour follow-up post-infusion

Population: Efficacy population was defined as all participants in the safety population who completed ≥12 hours of infusion and had efficacy evaluations through the 12-hour visits in both Treatment Periods 1 and 2 of Stage 1.

The TETRAS PS total score was calculated as the sum of items 4 (upper-limb), 6 (Archimedes spiral), 7 (handwriting), and 8 (dot approximation). TETRAS PS upper-limb total score was calculated as the sum of the 6 separate upper-limb maneuvers assessed by the clinician: forward-outstretched postural tremor \[right\], forward outstretched postural tremor \[left\], lateral wing-beating postural tremor \[right\], lateral wing-beating postural tremor \[left\], kinetic tremor \[right\], kinetic tremor \[left\], each on a 0 (no tremor) to 4 (maximum tremor) severity scale in 0.5-point increments. TETRAS Part 4 score for both upper limbs ranged from 0 to 24, higher scores indicated more severe tremor. A negative change from baseline indicated less tremor. Baseline is defined as the pre-infusion value in each period/stage.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in The Essential Tremor Rating Scale (TETRAS) Using Performance Subscale (PS) Part 4 Upper-Limb Total Scores Pre-infusion	9.48 score on a scale Standard Deviation 3.917	9.72 score on a scale Standard Deviation 3.199
Stage 1: Change From Baseline in The Essential Tremor Rating Scale (TETRAS) Using Performance Subscale (PS) Part 4 Upper-Limb Total Scores CFB at 2 Hours	-2.10 score on a scale Standard Deviation 2.309	-2.10 score on a scale Standard Deviation 1.860
Stage 1: Change From Baseline in The Essential Tremor Rating Scale (TETRAS) Using Performance Subscale (PS) Part 4 Upper-Limb Total Scores CFB at 4 Hours	-2.06 score on a scale Standard Deviation 2.205	-2.72 score on a scale Standard Deviation 2.107
Stage 1: Change From Baseline in The Essential Tremor Rating Scale (TETRAS) Using Performance Subscale (PS) Part 4 Upper-Limb Total Scores CFB at 6 Hours	-2.94 score on a scale Standard Deviation 2.007	-1.84 score on a scale Standard Deviation 1.553
Stage 1: Change From Baseline in The Essential Tremor Rating Scale (TETRAS) Using Performance Subscale (PS) Part 4 Upper-Limb Total Scores CFB at 8 Hours	-2.94 score on a scale Standard Deviation 2.682	-2.74 score on a scale Standard Deviation 1.943
Stage 1: Change From Baseline in The Essential Tremor Rating Scale (TETRAS) Using Performance Subscale (PS) Part 4 Upper-Limb Total Scores CFB at 10 Hours	-2.94 score on a scale Standard Deviation 2.505	-2.60 score on a scale Standard Deviation 1.898
Stage 1: Change From Baseline in The Essential Tremor Rating Scale (TETRAS) Using Performance Subscale (PS) Part 4 Upper-Limb Total Scores CFB at 12 Hours	-3.48 score on a scale Standard Deviation 2.632	-2.46 score on a scale Standard Deviation 2.031
Stage 1: Change From Baseline in The Essential Tremor Rating Scale (TETRAS) Using Performance Subscale (PS) Part 4 Upper-Limb Total Scores CFB at 12-hour Follow-up	-1.38 score on a scale Standard Deviation 1.943	-1.70 score on a scale Standard Deviation 1.507

SECONDARY outcome

Timeframe: Stage 2 Day 1: Baseline and at 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours

Population: Efficacy population was participants from safety population, who completed ≥12 hours of infusion and had efficacy evaluations through the 12-hour visits in both Treatment Periods 1 and 2, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

The TETRAS PS total score was calculated as the sum of items 4 (upper-limb), 6 (Archimedes spiral), 7 (handwriting), and 8 (dot approximation). TETRAS PS upper-limb total score was calculated as the sum of the 6 separate upper-limb maneuvers assessed by the clinician: forward-outstretched postural tremor \[right\], forward outstretched postural tremor \[left\], lateral wing-beating postural tremor \[right\], lateral wing-beating postural tremor \[left\], kinetic tremor \[right\], kinetic tremor \[left\], each on a 0 (no tremor) to 4 (maximum tremor) severity scale in 0.5-point increments. TETRAS Part 4 score for both upper limbs ranged from 0 to 24, higher scores indicated more severe tremor. A negative change from baseline indicated less tremor.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores Baseline	9.24 score on a scale Standard Deviation 1.977	—
Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores CFB at 2 Hours	-1.66 score on a scale Standard Deviation 2.173	—
Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores CFB at 3 Hours	-2.44 score on a scale Standard Deviation 2.542	—
Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores CFB at 4 Hours	-3.25 score on a scale Standard Deviation 2.550	—
Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores CFB at 6 Hours	-2.66 score on a scale Standard Deviation 2.612	—
Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores CFB at 8 Hours	-3.16 score on a scale Standard Deviation 2.809	—
Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores CFB at 10 Hours	-2.19 score on a scale Standard Deviation 1.642	—
Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores CFB at 12 Hours	-1.25 score on a scale Standard Deviation 1.602	—
Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores CFB at 14 Hours	-0.66 score on a scale Standard Deviation 1.091	—
Stage 2: Change From Baseline in TETRAS Using PS Part 4 Upper-Limb Total Scores CFB at 24 Hours	-0.84 score on a scale Standard Deviation 1.850	—

SECONDARY outcome

Timeframe: Stage 1 Day 1 and 10: Pre-infusion (Baseline) and 2, 4, 6, 8, 10 and 12 hours and 12-hour follow-up post-infusion

Population: Efficacy population was defined as all participants in the safety population who completed ≥12 hours of infusion and had efficacy evaluations through the 12-hour visits in both Treatment Periods 1 and 2 of Stage 1. Overall number of participants analyzed = Number of participants analyzed in this outcome measure.

SSS is a participant-rated scale designed to quickly assess how alert a participant was feeling. Degrees of sleepiness and alertness were rated on a scale of 1 to 7, where the lowest score of '1' indicated the participant was 'feeling active, vital, alert, or wide awake' and the highest score of '7' indicated the participant was 'no longer fighting sleep, sleep onset soon; having dream-like thoughts'. Baseline is defined as the pre-infusion value in each period. A negative change from baseline indicated less sleepiness.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=24 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 Participants Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Change From Baseline in Stanford Sleepiness Scale (SSS) Score Pre-infusion	1.6 score on a scale Standard Deviation 0.77	1.6 score on a scale Standard Deviation 0.76
Stage 1: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 2 Hours	0.3 score on a scale Standard Deviation 1.37	0.0 score on a scale Standard Deviation 0.41
Stage 1: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 4 Hours	0.3 score on a scale Standard Deviation 1.40	0.1 score on a scale Standard Deviation 0.53
Stage 1: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 6 Hours	0.7 score on a scale Standard Deviation 1.09	0.1 score on a scale Standard Deviation 0.83
Stage 1: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 8 Hours	0.1 score on a scale Standard Deviation 1.08	0.0 score on a scale Standard Deviation 0.82
Stage 1: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 10 Hours	0.3 score on a scale Standard Deviation 1.40	0.2 score on a scale Standard Deviation 0.93
Stage 1: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 12 Hours	0.2 score on a scale Standard Deviation 0.87	-0.0 score on a scale Standard Deviation 0.89
Stage 1: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 12-hour Follow-up	-0.1 score on a scale Standard Deviation 0.54	-0.2 score on a scale Standard Deviation 0.75

SECONDARY outcome

Timeframe: Stage 2 Day 1: Baseline and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 hours

Population: Efficacy population was participants from safety population who completed ≥12 hours of infusion and had efficacy evaluations through the 12-hour visits in both Treatment Periods 1 and 2, who received study drug in Stage 2. Number analyzed = Number of participants with data available at the specific time point.

SSS is a participant-rated scale designed to quickly assess how alert a participant was feeling. Degrees of sleepiness and alertness were rated on a scale of 1 to 7, where the lowest score of '1' indicated the participant was 'feeling active, vital, alert, or wide awake' and the highest score of '7' indicated the participant was 'no longer fighting sleep, sleep onset soon; having dream-like thoughts'. Baseline is defined as the pre-infusion value in each period. A negative change from baseline indicated less sleepiness.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score Baseline	1.5 score on a scale Standard Deviation 0.62	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 1 Hour	0.4 score on a scale Standard Deviation 1.12	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 2 Hours	1.4 score on a scale Standard Deviation 1.09	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 3 Hours	2.5 score on a scale Standard Deviation 2.10	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 4 Hours	3.1 score on a scale Standard Deviation 1.81	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 5 Hours	3.3 score on a scale Standard Deviation 2.02	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 6 Hours	3.3 score on a scale Standard Deviation 1.91	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 7 Hours	2.6 score on a scale Standard Deviation 1.79	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 8 Hours	2.4 score on a scale Standard Deviation 1.86	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 9 Hours	2.3 score on a scale Standard Deviation 1.91	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 10 Hours	2.0 score on a scale Standard Deviation 1.97	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 11 Hours	0.1 score on a scale Standard Deviation 0.85	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 12 Hours	-0.3 score on a scale Standard Deviation 0.86	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 14 Hours	0.3 score on a scale Standard Deviation 1.44	—
Stage 2: Change From Baseline in Stanford Sleepiness Scale (SSS) Score CFB at 24 Hours	-0.3 score on a scale Standard Deviation 0.86	—

SECONDARY outcome

Timeframe: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours

Population: Pharmacokinetic (PK) population was defined as all safety population participants who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 of Stage 1 with sufficient plasma concentrations for PK evaluation.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Maximum Peak Plasma Concentration (Cmax) of SAGE-547	84.3 nanograms per milliliter (ng/mL) Standard Deviation 28.2	—

SECONDARY outcome

Timeframe: Stage 2: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion

Population: PK population was participants from safety population, who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 with sufficient plasma concentrations for PK evaluation, who received study drug in Stage 2.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Maximum Peak Plasma Concentration (Cmax) of SAGE-547	152 ng/mL Standard Deviation 36	—

SECONDARY outcome

Timeframe: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours

Population: PK population was defined as all safety population participants who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 of Stage 1 with sufficient plasma concentrations for PK evaluation.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Time to Maximum Peak Plasma Concentration (Cmax) of SAGE-547	10 hours Interval 1.0 to 12.483	—

SECONDARY outcome

Timeframe: Stage 2: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion

Population: PK population was participants from safety population, who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 with sufficient plasma concentrations for PK evaluation, who received study drug in Stage 2.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Time to Maximum Peak Plasma Concentration (Cmax) of SAGE-547	6 hours Interval 2.967 to 9.05	—

SECONDARY outcome

Timeframe: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours

Population: PK population was defined as all safety population participants who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 of Stage 1 with sufficient plasma concentrations for PK evaluation.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Area Under the Plasma Concentration Time Curve up to the Time of the Last Quantifiable Sample (AUClast) of SAGE-547	654 nanogramshours per milliliter (ngh/mL) Standard Deviation 251	—

SECONDARY outcome

Timeframe: Day 1: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion

Population: PK population was participants from safety population, who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 with sufficient plasma concentrations for PK evaluation, who received study drug in Stage 2.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Area Under the Plasma Concentration Time Curve up to the Time of the Last Quantifiable Sample (AUClast) of SAGE-547	1310 ng*h/mL Standard Deviation 300	—

SECONDARY outcome

Timeframe: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours

Population: PK population was defined as all safety population participants who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 of Stage 1 with sufficient plasma concentrations for PK evaluation.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of SAGE-547	716 ng*h/mL Standard Deviation 286	—

SECONDARY outcome

Timeframe: Stage 2: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion

Population: PK population was participants from safety population, who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 with sufficient plasma concentrations for PK evaluation, who received study drug in Stage 2.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of SAGE-547	1380 ng*h/mL Standard Deviation 300	—

SECONDARY outcome

Timeframe: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours

Population: PK population was defined as all safety population participants who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 of Stage 1 with sufficient plasma concentrations for PK evaluation.

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

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Clearance (CL) of SAGE-547	1.09 liters per hour per kilogram (L/h/kg) Standard Deviation 0.41	—

SECONDARY outcome

Timeframe: Stage 2: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion

Population: PK population was participants from safety population, who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 with sufficient plasma concentrations for PK evaluation, who received study drug in Stage 2.

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

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Clearance (CL) of SAGE-547	1.07 L/h/kg Standard Deviation 0.28	—

SECONDARY outcome

Timeframe: Stage 1: Pre-infusion and after the start of infusion at 30 and 40 minutes and at 1, 1.5, 2, 4, 6, 8, 10, 12, 12.5, 12.75, 13, 13.5, 14, 16 and 24 hours

Population: PK population was defined as all safety population participants who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 of Stage 1 with sufficient plasma concentrations for PK evaluation.

Terminal half-life is defined as the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=25 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 1: Terminal Half-Life (t½) of SAGE-547	5.6 hours Interval 1.8 to 12.8	—

SECONDARY outcome

Timeframe: Stage 2: Pre-infusion and at 30, 60, 90 and 120 minutes and at 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 10.5, 10.75, 11, 11.5, 12, 14, 16 and 24 hours after start of the infusion

Population: PK population was defined as all safety population participants who completed at least 12 hours of SAGE-547 infusion in Treatment Period 1 or Treatment Period 2 of Stage 1 with sufficient plasma concentrations for PK evaluation.

Terminal half-life is defined as the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.

Outcome measures

Outcome measures
Measure	Stage 1: SAGE-547 n=17 Participants Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).
Stage 2: Terminal Half-Life (t½) of SAGE-547	7.6 hours Interval 4.8 to 9.5	—

Adverse Events

Stage 1: SAGE-547

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Stage 1: Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Stage 2: SAGE-547

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Stage 1: SAGE-547 n=25 participants at risk Participants received a 12-hour IV infusion of SAGE 547, at ascending doses of 29, 58, and 86 μg/kg/h, 4 hours each, on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 1: Placebo n=25 participants at risk Participants received a 12-hour IV infusion of SAGE-547 matching-placebo on Day 1 of Stage 1 (TP 1) or on Day 10 of Stage 1 (TP 2).	Stage 2: SAGE-547 n=17 participants at risk Participants who completed Stage 1 received a 10-hour IV infusion of SAGE 547, at ascending doses of 90 μg/kg/h for 1 hour, 120 μg/kg/h for 1 hour, and 150 μg/kg/h for 8 hours on Day 1 of Stage 2.
General disorders Fatigue	4.0% 1/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	23.5% 4/17 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	5.9% 1/17 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	5.9% 1/17 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.
Nervous system disorders Dizziness	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	8.0% 2/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	17.6% 3/17 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.
Nervous system disorders Headache	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	4.0% 1/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	5.9% 1/17 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.
Nervous system disorders Sedation	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	5.9% 1/17 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.
Vascular disorders Hypotension	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	0.00% 0/25 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.	5.9% 1/17 • Stage 1: Up to 30 days after last infusion (up to Day 40); Stage 2: Up to 30 days after last infusion (up to Day 31) Safety population for Stage 1 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1 of Stage 1. The safety population for Stage 2 included all participants admitted into the inpatient unit who met all eligibility criteria, signed an informed consent, and who began infusion with SAGE-547 or placebo in Treatment Period 1, who received study drug in Stage 2.

Additional Information

Medical Monitor

Sage Therapeutics

Phone: (617) 299-8380

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER