Trial Outcomes & Findings for Evaluate SAGE-547 in Female Participants With Severe Postpartum Depression (NCT NCT02285504)

NCT ID: NCT02285504

Last Updated: 2025-09-15

Results Overview

AEs were any untoward medical occurrences in a participant who received study treatment without regard to possibility of causal relationship. TEAEs were defined as AEs with onset after the start of SAGE-547 infusion, or any worsening of a pre-existing medical condition or AEs with onset after the start of SAGE-547 infusion and until 7 days after the end of infusion (Day 11). TESAEs were defined as AEs with onset after the start of SAGE-547 infusion, or any worsening of a pre-existing medical condition or AEs with onset after the start of SAGE-547 infusion and until 30 days after the end of infusion (Day 34).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

TEAEs: Up to Day 11, TESAEs: Up to Day 34

Results posted on

2025-09-15

Participant Flow

Participants were enrolled in the study at 1 center in the United States from 07 January 2015 to 05 June 2015.

A total of 6 participants were screened, 4 participants were treated and completed the study. This study consisted of up to a 3-day screening period, a 4-day (84-hour) active treatment period, a 7-day adverse event (AE) follow-up period, plus an additional 23 days of serious AE follow-up (with a telephone call at Day 11 and Day 34).

Participant milestones

Participant milestones
Measure
SAGE-547
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 micrograms per kilogram per hour \[mcg/kg/hr\] \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Overall Study
STARTED
4
Overall Study
COMPLETED
4
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluate SAGE-547 in Female Participants With Severe Postpartum Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Age, Continuous
32.0 years
STANDARD_DEVIATION 6.88 • n=5 Participants
Sex: Female, Male
Female
4 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
4 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=5 Participants
Race (NIH/OMB)
White
3 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: TEAEs: Up to Day 11, TESAEs: Up to Day 34

Population: Safety population included all participants who began infusion with SAGE-547 injection.

AEs were any untoward medical occurrences in a participant who received study treatment without regard to possibility of causal relationship. TEAEs were defined as AEs with onset after the start of SAGE-547 infusion, or any worsening of a pre-existing medical condition or AEs with onset after the start of SAGE-547 infusion and until 7 days after the end of infusion (Day 11). TESAEs were defined as AEs with onset after the start of SAGE-547 infusion, or any worsening of a pre-existing medical condition or AEs with onset after the start of SAGE-547 infusion and until 30 days after the end of infusion (Day 34).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
TEAEs
4 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
TESAEs
0 Participants

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: Chemistry (ALT, AST, GGT) expressed in terms of units per liter (U/L). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)
Change From Baseline at Day 2 (24 hrs): ALT
-3.0 U/L
Standard Deviation 4.69
Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)
Change From Baseline at Day 3 (48 hrs): ALT
-3.7 U/L
Standard Deviation 7.02
Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)
Change From Baseline at Day 4 (84 hrs): ALT
2.7 U/L
Standard Deviation 2.08
Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)
Change From Baseline at Day 2 (24 hrs): AST
-0.5 U/L
Standard Deviation 6.19
Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)
Change From Baseline at Day 3 (48 hrs): AST
1.0 U/L
Standard Deviation 6.24
Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)
Change From Baseline at Day 4 (84 hrs): AST
4.7 U/L
Standard Deviation 5.69
Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)
Change From Baseline at Day 2 (24 hrs): GGT
-0.7 U/L
Standard Deviation 2.08
Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)
Change From Baseline at Day 3 (48 hrs): GGT
-2.0 U/L
Standard Deviation 1.41
Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)
Change From Baseline at Day 4 (84 hrs): GGT
5.5 U/L
Standard Deviation 9.19

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: Chemistry (carbon dioxide \[CO2\], sodium, potassium and chloride) expressed in terms of millimoles/liter (mmol/L). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 3 (48 hrs): Chloride
-1.3 mmol/L
Standard Deviation 5.03
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 4 (84 hrs): Chloride
-1.3 mmol/L
Standard Deviation 6.03
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 2 (24 hrs): CO2
-0.5 mmol/L
Standard Deviation 3.42
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 3 (48 hrs): CO2
-2.0 mmol/L
Standard Deviation 3.61
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 4 (84 hrs): CO2
-3.0 mmol/L
Standard Deviation 4.58
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 2 (24 hrs): Sodium
-0.5 mmol/L
Standard Deviation 1.00
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 3 (48 hrs): Sodium
-1.3 mmol/L
Standard Deviation 2.08
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 4 (84 hrs): Sodium
1.3 mmol/L
Standard Deviation 2.52
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 2 (24 hrs): Potassium
0.25 mmol/L
Standard Deviation 0.208
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 3 (48 hrs): Potassium
0.20 mmol/L
Standard Deviation 0.100
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 4 (84 hrs): Potassium
0.47 mmol/L
Standard Deviation 0.115
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
Change From Baseline at Day 2 (24 hrs): Chloride
-0.5 mmol/L
Standard Deviation 5.00

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: Chemistry (glucose, total bilirubin, calcium, blood urea nitrogen \[BUN\] and creatinine) expressed in terms of milligrams/deciliter (mg/dL). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 2 (24 hrs): Calcium
-0.28 mg/dL
Standard Deviation 0.532
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 4 (84 hrs): Calcium
0.30 mg/dL
Standard Deviation 0.265
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 2 (24 hrs): BUN
0.5 mg/dL
Standard Deviation 1.29
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 3 (48 hrs): BUN
0.3 mg/dL
Standard Deviation 4.51
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 4 (84 hrs): BUN
0.0 mg/dL
Standard Deviation 4.58
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 2 (24 hrs): Creatinine
-0.010 mg/dL
Standard Deviation 0.0698
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 3 (48 hrs): Creatinine
-0.050 mg/dL
Standard Deviation 0.0721
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 4 (84 hrs): Creatinine
-0.057 mg/dL
Standard Deviation 0.1159
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 4 (84 hrs): Glucose
17.7 mg/dL
Standard Deviation 13.58
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 2 (24 hrs): Total Bilirubin
-0.05 mg/dL
Standard Deviation 0.129
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 3 (48 hrs): Total Bilirubin
-0.23 mg/dL
Standard Deviation 0.153
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 4 (84 hrs): Total Bilirubin
-0.13 mg/dL
Standard Deviation 0.115
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 2 (24 hrs): Glucose
16.0 mg/dL
Standard Deviation 15.90
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 3 (48 hrs): Glucose
28.3 mg/dL
Standard Deviation 31.37
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
Change at Day 3 (48 hrs): Calcium
-0.03 mg/dL
Standard Deviation 0.802

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: Chemistry (albumin, total protein), Hematology and Coagulation (hemoglobin) expressed in terms of g/dL. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin
Change at Day 2 (24 hrs): Albumin
-0.40 g/dL
Standard Deviation 0.497
Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin
Change at Day 3 (48 hrs): Albumin
-0.33 g/dL
Standard Deviation 0.551
Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin
Change at Day 4 (84 hrs): Albumin
0.20 g/dL
Standard Deviation 0.173
Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin
Change at Day 2 (24 hrs): Total Protein
-0.63 g/dL
Standard Deviation 0.499
Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin
Change at Day 2 (24 hrs): Hemoglobin
0.02 g/dL
Standard Deviation 0.943
Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin
Change at Day 3 (48 hrs): Hemoglobin
-0.10 g/dL
Standard Deviation 0.954
Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin
Change at Day 4 (84 hrs): Hemoglobin
0.27 g/dL
Standard Deviation 0.306
Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin
Change at Day 3 (48 hrs): Total Protein
-0.43 g/dL
Standard Deviation 0.702
Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin
Change at Day 4 (84 hrs): Total Protein
0.20 g/dL
Standard Deviation 0.361

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: Hematocrit expressed in terms of percentage. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measure: Hematocrit
Change From Baseline at Day 4 (84 hrs)
1.20 percentage of hematocrit
Standard Deviation 1.311
Change From Baseline in Clinical Laboratory Measure: Hematocrit
Change From Baseline at Day 2 (24 hrs)
0.15 percentage of hematocrit
Standard Deviation 2.199
Change From Baseline in Clinical Laboratory Measure: Hematocrit
Change From Baseline at Day 3 (48 hrs)
-1.07 percentage of hematocrit
Standard Deviation 1.914

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: Platelet count, white blood cells (WBC), absolute lymphocytes, absolute neutrophils, absolute basophils, absolute eosinophils, absolute monocytes expressed in terms of 10\^9 cells/L. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 4 (84 hrs): Absolute Lymphocytes
-0.57 10^9 cells/L
Standard Deviation 0.737
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 2 (24 hrs): Absolute Neutrophils
-0.933 10^9 cells/L
Standard Deviation 0.2082
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 2 (24 hrs): Absolute Lymphocytes
-0.73 10^9 cells/L
Standard Deviation 0.764
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 3 (48 hrs): Absolute Lymphocytes
-0.50 10^9 cells/L
Standard Deviation 1.273
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 3 (48 hrs): Absolute Neutrophils
-1.250 10^9 cells/L
Standard Deviation 0.2121
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 4 (84 hrs): Absolute Neutrophils
-0.467 10^9 cells/L
Standard Deviation 0.2082
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 4 (84 hrs): Absolute Basophils
0.0 10^9 cells/L
Standard Deviation 0.00
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 2 (24 hrs): Absolute Eosinophils
0.03 10^9 cells/L
Standard Deviation 0.058
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 3 (48 hrs): Absolute Eosinophils
0.05 10^9 cells/L
Standard Deviation 0.071
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 4 (84 hrs): Absolute Eosinophils
0.00 10^9 cells/L
Standard Deviation 0.100
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 2 (24 hrs): Absolute Monocytes
-0.10 10^9 cells/L
Standard Deviation 0.100
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 4 (84 hrs): Absolute Monocytes
-0.07 10^9 cells/L
Standard Deviation 0.058
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 2 (24 hrs): Platelet Count
-18.8 10^9 cells/L
Standard Deviation 16.50
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 3 (48 hrs): Platelet Count
-23.3 10^9 cells/L
Standard Deviation 27.65
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 4 (84 hrs): Platelet Count
-4.3 10^9 cells/L
Standard Deviation 37.98
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 2 (24 hrs): WBC
-0.93 10^9 cells/L
Standard Deviation 1.910
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 3 (48 hrs): WBC
-0.03 10^9 cells/L
Standard Deviation 3.287
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 2 (24 hrs): Absolute Basophils
0.0 10^9 cells/L
Standard Deviation 0.00
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 3 (48 hrs): Absolute Basophils
0.0 10^9 cells/L
Standard Deviation 0.00
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 3 (48 hrs): Absolute Monocytes
-0.05 10^9 cells/L
Standard Deviation 0.071
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
Change at Day 4 (84 hrs): WBC
-1.07 10^9 cells/L
Standard Deviation 1.069

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: RBC expressed in terms of 10\^12 cells/L. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measure: Red Blood Cells (RBC)
Change From Baseline at Day 2 (24 hrs)
-0.030 10^12 cells/L
Standard Deviation 0.1924
Change From Baseline in Clinical Laboratory Measure: Red Blood Cells (RBC)
Change From Baseline at Day 3 (48 hrs)
-0.090 10^12 cells/L
Standard Deviation 0.2784
Change From Baseline in Clinical Laboratory Measure: Red Blood Cells (RBC)
Change From Baseline at Day 4 (84 hrs)
0.113 10^12 cells/L
Standard Deviation 0.1656

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: MCV expressed in terms of femtoliters (fL). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Volume (MCV)
Change From Baseline at Day 2 (24 hrs)
0.85 fL
Standard Deviation 1.578
Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Volume (MCV)
Change From Baseline at Day 3 (48 hrs)
-0.53 fL
Standard Deviation 0.924
Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Volume (MCV)
Change From Baseline at Day 4 (84 hrs)
0.33 fL
Standard Deviation 1.155

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: MCH expressed in terms of picogram (pg). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Hemoglobin (MCH)
Change From Baseline at Day 2 (24 hrs)
-0.3 pg
Standard Deviation 1.15
Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Hemoglobin (MCH)
Change From Baseline at Day 3 (48 hrs)
0.5 pg
Standard Deviation 0.71
Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Hemoglobin (MCH)
Change From Baseline at Day 4 (84 hrs)
-0.3 pg
Standard Deviation 1.15

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: PT/INR expressed in terms of seconds. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measure: Prothrombin Time/International Normalized Ratio (PT/INR)
Change From Baseline at Day 2 (24 hrs)
-0.30 seconds
Standard Deviation 0.700
Change From Baseline in Clinical Laboratory Measure: Prothrombin Time/International Normalized Ratio (PT/INR)
Change From Baseline at Day 3 (48 hrs)
-1.05 seconds
Standard Deviation 0.636
Change From Baseline in Clinical Laboratory Measure: Prothrombin Time/International Normalized Ratio (PT/INR)
Change From Baseline at Day 4 (84 hrs)
-0.37 seconds
Standard Deviation 0.902

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: Urinalysis (pH). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measure: Potential of Hydrogen (pH)
Change From Baseline at Day 2 (24 hrs)
-0.17 pH
Standard Deviation 1.155
Change From Baseline in Clinical Laboratory Measure: Potential of Hydrogen (pH)
Change From Baseline at Day 3 (48 hrs)
0.33 pH
Standard Deviation 0.289
Change From Baseline in Clinical Laboratory Measure: Potential of Hydrogen (pH)
Change From Baseline at Day 4 (84 hrs)
1.00 pH
Standard Deviation 0.000

PRIMARY outcome

Timeframe: Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Clinical laboratory evaluation included: Urinalysis (specific gravity) expressed in terms of ratio. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Clinical Laboratory Measure: Specific Gravity
Change From Baseline at Day 2 (24 hrs)
-0.0080 ratio
Standard Deviation 0.00458
Change From Baseline in Clinical Laboratory Measure: Specific Gravity
Change From Baseline at Day 3 (48 hrs)
-0.0017 ratio
Standard Deviation 0.00252
Change From Baseline in Clinical Laboratory Measure: Specific Gravity
Change From Baseline at Day 4 (84 hrs)
-0.0015 ratio
Standard Deviation 0.00495

PRIMARY outcome

Timeframe: Baseline, Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Vital sign parameters included supine systolic blood pressure (SBP), supine diastolic blood pressure (DBP), standing systolic blood pressure and standing diastolic blood pressure expressed in terms of millimeters of mercury (mmHg). The data was collected at time-points on Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 4 (84 hrs): Supine DBP
7.5 mmHg
Standard Deviation 10.21
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 1 (12 hrs): Supine SBP
-2.8 mmHg
Standard Deviation 13.65
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 2 (24 hrs): Supine SBP
2.3 mmHg
Standard Deviation 11.95
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 2 (36 hrs): Supine SBP
-1.0 mmHg
Standard Deviation 15.19
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 3 (48 hrs): Supine SBP
-5.0 mmHg
Standard Deviation 4.40
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 3 (60 hrs): Supine SBP
12.3 mmHg
Standard Deviation 17.75
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 4 (72 hrs): Supine SBP
5.0 mmHg
Standard Deviation 23.73
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 4 (84 hrs): Supine SBP
8.0 mmHg
Standard Deviation 20.69
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 1 (12 hrs): Supine DBP
-1.3 mmHg
Standard Deviation 12.50
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 2 (24 hrs): Supine DBP
3.0 mmHg
Standard Deviation 6.83
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 2 (36 hrs): Supine DBP
-2.3 mmHg
Standard Deviation 5.68
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 3 (48 hrs): Supine DBP
-5.0 mmHg
Standard Deviation 5.42
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 3 (60 hrs): Supine DBP
4.0 mmHg
Standard Deviation 6.22
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 4 (72 hrs): Supine DBP
0.5 mmHg
Standard Deviation 9.75
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 1(12 hrs):Standing SBP
-4.0 mmHg
Standard Deviation 7.87
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 2(24 hrs):Standing SBP
-1.5 mmHg
Standard Deviation 8.23
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 2(36 hrs):Standing SBP
-0.8 mmHg
Standard Deviation 7.27
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 3(48 hrs):Standing SBP
-1.5 mmHg
Standard Deviation 7.68
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 3(60 hrs):Standing SBP
16.8 mmHg
Standard Deviation 2.50
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 4(72 hrs):Standing SBP
0.3 mmHg
Standard Deviation 11.53
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 4(84 hrs):Standing SBP
-0.7 mmHg
Standard Deviation 8.74
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 1(12 hrs):Standing DBP
1.0 mmHg
Standard Deviation 8.52
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 2(24 hrs):Standing DBP
6.3 mmHg
Standard Deviation 4.11
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 2(36 hrs):Standing DBP
1.5 mmHg
Standard Deviation 9.11
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 3(48 hrs):Standing DBP
7.5 mmHg
Standard Deviation 5.92
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 3(60 hrs):Standing DBP
13.8 mmHg
Standard Deviation 8.81
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 4(72 hrs):Standing DBP
13.3 mmHg
Standard Deviation 8.14
Change From Baseline in Vital Sign: Blood Pressure
Change From Baseline at Day 4(84 hrs):Standing DBP
10.3 mmHg
Standard Deviation 3.06

PRIMARY outcome

Timeframe: Baseline, Day 1 (12 hrs) Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection.

Vital sign parameter included heart rate expressed in terms of beats per minute (bpm). The data was collected at time-points on Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Vital Sign: Heart Rate
Change From Baseline at Day 1 (12 hrs)
-2.5 bpm
Standard Deviation 15.35
Change From Baseline in Vital Sign: Heart Rate
Change From Baseline at Day 2 (24 hrs)
5.3 bpm
Standard Deviation 18.84
Change From Baseline in Vital Sign: Heart Rate
Change From Baseline at Day 2 (36 hrs)
-2.3 bpm
Standard Deviation 11.44
Change From Baseline in Vital Sign: Heart Rate
Change From Baseline at Day 3 (48 hrs)
-1.5 bpm
Standard Deviation 11.56
Change From Baseline in Vital Sign: Heart Rate
Change From Baseline at Day 3 (60 hrs)
-3.0 bpm
Standard Deviation 8.41
Change From Baseline in Vital Sign: Heart Rate
Change From Baseline at Day 4 (72 hrs)
-5.8 bpm
Standard Deviation 7.63
Change From Baseline in Vital Sign: Heart Rate
Change From Baseline at Day 4 (84 hrs)
-0.8 bpm
Standard Deviation 4.99

PRIMARY outcome

Timeframe: Baseline, Day 1 (12 hrs) Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection.

Vital sign parameter included temperature expressed in terms of degree Celsius. The data was collected at time-points on Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Vital Sign: Body Temperature
Change From Baseline at Day 1 (12 hrs)
-0.20 degree Celsius
Standard Deviation 0.32
Change From Baseline in Vital Sign: Body Temperature
Change From Baseline at Day 2 (24 hrs)
0.15 degree Celsius
Standard Deviation 0.23
Change From Baseline in Vital Sign: Body Temperature
Change From Baseline at Day 2 (36 hrs)
-0.15 degree Celsius
Standard Deviation 0.33
Change From Baseline in Vital Sign: Body Temperature
Change From Baseline at Day 3 (48 hrs)
-0.05 degree Celsius
Standard Deviation 0.25
Change From Baseline in Vital Sign: Body Temperature
Change From Baseline at Day 3 (60 hrs)
0.03 degree Celsius
Standard Deviation 0.31
Change From Baseline in Vital Sign: Body Temperature
Change From Baseline at Day 4 (72 hrs)
-0.30 degree Celsius
Standard Deviation 0.37
Change From Baseline in Vital Sign: Body Temperature
Change From Baseline at Day 4 (84 hrs)
-0.45 degree Celsius
Standard Deviation 0.46

PRIMARY outcome

Timeframe: Baseline, Day 1 (12 hrs) Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection. Here, 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.

Vital sign parameter included respiratory rate expressed in terms of breaths per minute. The data was collected at time-points on Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Vital Sign: Respiratory Rate
Change From Baseline at Day 1 (12 hrs)
0.0 breaths/min
Standard Deviation 1.63
Change From Baseline in Vital Sign: Respiratory Rate
Change From Baseline at Day 2 (24 hrs)
0.0 breaths/min
Standard Deviation 2.31
Change From Baseline in Vital Sign: Respiratory Rate
Change From Baseline at Day 2 (36 hrs)
0.0 breaths/min
Standard Deviation 2.31
Change From Baseline in Vital Sign: Respiratory Rate
Change From Baseline at Day 3 (48 hrs)
0.0 breaths/min
Standard Deviation 4.00
Change From Baseline in Vital Sign: Respiratory Rate
Change From Baseline at Day 3 (60 hrs)
0.3 breaths/min
Standard Deviation 1.53
Change From Baseline in Vital Sign: Respiratory Rate
Change From Baseline at Day 4 (72 hrs)
-1.0 breaths/min
Standard Deviation 1.15
Change From Baseline in Vital Sign: Respiratory Rate
Change From Baseline at Day 4 (84 hrs)
-0.5 breaths/min
Standard Deviation 1.00

PRIMARY outcome

Timeframe: Baseline, Day 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection.

ECGs parameters included QT interval, PR interval, QTc interval, QRS duration expressed in terms of milliseconds (msec).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Electrocardiogram (ECG) Parameters: QT Interval, PR Interval, QTc Interval, and QRS Duration
Change from Baseline at Day 4 (84 hrs):QT Interval
-28.5 msec
Standard Deviation 34.31
Change From Baseline in Electrocardiogram (ECG) Parameters: QT Interval, PR Interval, QTc Interval, and QRS Duration
Change from Baseline at Day 4 (84 hrs):PR Interval
-1.0 msec
Standard Deviation 9.87
Change From Baseline in Electrocardiogram (ECG) Parameters: QT Interval, PR Interval, QTc Interval, and QRS Duration
Change from Baseline at Day 4(84 hrs):QTc Interval
13.3 msec
Standard Deviation 10.44
Change From Baseline in Electrocardiogram (ECG) Parameters: QT Interval, PR Interval, QTc Interval, and QRS Duration
Change from Baseline at Day 4(84 hrs):QRS Duration
-3.5 msec
Standard Deviation 7.19

PRIMARY outcome

Timeframe: Baseline, Day 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection.

ECGs parameter included heart rate expressed in terms of beats per minute (bpm).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate
14.3 bpm
Standard Deviation 9.29

PRIMARY outcome

Timeframe: At Day 4

Population: Safety population included all participants who began infusion with SAGE-547 injection.

Physical examinations included body weight, height, body mass index (BMI) and assessment of body systems (e.g., head, eyes, ears, nose, throat, lungs, abdomen, and extremities) as well as cognitive and mental health examinations (components of the neurological and psychiatric examinations, respectively).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Number of Participants With Physical Examination Findings
4 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 11

Population: Safety population included all participants who began infusion with SAGE-547 injection.

Concomitant medications are other prescription medications, over the counter (OTC) drugs or dietary supplements that a study participant takes in addition to the drug under investigation.

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Number of Participants With Concomitant Medication Usage
3 Participants

PRIMARY outcome

Timeframe: Pre-infusion (Day 1 prior to dosing), Post-infusion (any time after the start of infusion on Day 1 up to 84 hrs)

Population: Efficacy population included all participants who began infusion with SAGE-547 injection and who completed at least 12 hours of infusion and have efficacy evaluations through the 12-hour visit.

C-SSRS scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicidal ideation and behavior, and a post-baseline evaluation that focuses on suicidality since the last study visit. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, (with score range from 1 to 5, higher score indicates more severity). The data was collected at time-points: Pre-infusion (Day 1 prior to dosing), Post-infusion (any time after the start of infusion on Day 1 up to 84 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
Pre-Infusion: Suicidal Ideation
3 Participants
Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
Post-Infusion: Suicidal Ideation
0 Participants
Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
Pre-Infusion: Suicidal Behavior
1 Participants
Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
Post-Infusion: Suicidal Behavior
0 Participants

SECONDARY outcome

Timeframe: Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose

Population: Pharmacokinetic (PK) population included all who began infusion with SAGE-547 injection and for whom at least one evaluable PK sample was available.

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Maximum Plasma Concentration (Cmax) of SAGE-547
97.2 nanograms per millilter (ng/mL)
Standard Deviation 77.3

SECONDARY outcome

Timeframe: Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose

Population: PK population included all who began infusion with SAGE-547 injection and for whom at least one evaluable PK sample was available.

Tmax is defined as the time at which Cmax of SAGE-547 occurred.

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Time to Maximum Plasma Concentration (Tmax) of SAGE-547
42 hours
Interval 12.0 to 48.0

SECONDARY outcome

Timeframe: Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose

Population: PK population included all who began infusion with SAGE-547 injection and for whom at least one evaluable PK sample was available.

AUCall is defined as the area under the plasma SAGE-547 concentration time curves from the start of the infusion until the time the last sample was taken 72 hours later.

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Area Under the Concentration-Time Curve From Start of the Infusion Until the Time of the Last Sample (AUCall) of SAGE-547
3380 nanograms*hour per milliliter (ng*hr/mL)
Standard Deviation 1410

SECONDARY outcome

Timeframe: Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, and 60 hrs post-dose

Population: PK population included all who began infusion with SAGE-547 injection and for whom at least one evaluable PK sample was available.

AUC0-60 is defined as the area under the plasma SAGE-547 concentration time curve during the intravenous infusion.

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Area Under the Concentration-Time Curve From Time Zero to 60 Hours (AUC0-60) of SAGE-547
3160 ng*hr/mL
Standard Deviation 1360

SECONDARY outcome

Timeframe: Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, and 24 hrs post-dose

Population: PK population included all who began infusion with SAGE-547 injection and for whom at least one evaluable PK sample was available. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

AUC24 is defined as the area under the plasma SAGE-547 concentration-time curve in a 24-hour period during the maintenance dose.

Outcome measures

Outcome measures
Measure
SAGE-547
n=3 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Area Under the Concentration-Time Curve in 24 Hours (AUC24) of SAGE-547
1590 ng*hr/mL
Standard Deviation 580

SECONDARY outcome

Timeframe: From 12 to 48 hrs (36 hr of maintenance dose period)

Population: PK population included all who began infusion with SAGE-547 injection and for whom at least one evaluable PK sample was available. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Cavg is defined as the plasma concentration of SAGE-547 at steady-state (average plasma concentration during the maintenance dose period; nominally 12 to 48 hrs).

Outcome measures

Outcome measures
Measure
SAGE-547
n=3 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Average Drug Concentration in the Plasma at Steady State During a Dosing Interval (Cavg) of SAGE-547
66.1 ng/mL
Standard Deviation 24.1

SECONDARY outcome

Timeframe: Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose

Population: PK population included all who began infusion with SAGE-547 injection and for whom at least one evaluable PK sample was available.

Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Plasma Clearance (CL) of SAGE-547
1.08 Liters per hour per kilogram (L/hr/kg)
Standard Deviation 0.22

SECONDARY outcome

Timeframe: Baseline, Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), Day 3 (at 48 and 60 hrs), and Day 4 (at 84 hrs)

Population: Safety population included all participants who began infusion with SAGE-547 injection.

The HAM-D-17 was used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D-17 is comprised of 17 individual items: Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis, where 0 indicated none/absent and higher scores indicated greater depression. The Total Score can range from 0 (least depression) to 52 (greater depression), and higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Change From Baseline in Hamilton Rating Scale for Depression-17 (HAM-D-17) Total Score
Change From Baseline at Day 3 (60 hrs)
-24.8 score on a scale
Standard Deviation 4.19
Change From Baseline in Hamilton Rating Scale for Depression-17 (HAM-D-17) Total Score
Change From Baseline at Day 2 (36 hrs)
-24.8 score on a scale
Standard Deviation 3.59
Change From Baseline in Hamilton Rating Scale for Depression-17 (HAM-D-17) Total Score
Change From Baseline at Day 3 (48 hrs)
-24.3 score on a scale
Standard Deviation 4.99
Change From Baseline in Hamilton Rating Scale for Depression-17 (HAM-D-17) Total Score
Change From Baseline at Day 4 (84 hrs)
-21.3 score on a scale
Standard Deviation 6.85
Change From Baseline in Hamilton Rating Scale for Depression-17 (HAM-D-17) Total Score
Change From Baseline at Day 1 (12 hrs)
-21.8 score on a scale
Standard Deviation 5.50
Change From Baseline in Hamilton Rating Scale for Depression-17 (HAM-D-17) Total Score
Change From Baseline at Day 2 (24 hrs)
-23.3 score on a scale
Standard Deviation 4.19

SECONDARY outcome

Timeframe: Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 84 hrs)

Population: Efficacy population included all participants who began infusion with SAGE-547 injection and who completed at least 12 hours of infusion and had efficacy evaluations through the 12-hour visit.

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

Outcome measures

Outcome measures
Measure
SAGE-547
n=4 Participants
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 mcg/kg/hr \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).
Clinical Global Impression-Improvement (CGI-I) Score
Day 1 (12 hrs)
1.8 score on a scale
Standard Deviation 0.50
Clinical Global Impression-Improvement (CGI-I) Score
Day 2 (24 hrs)
1.3 score on a scale
Standard Deviation 0.50
Clinical Global Impression-Improvement (CGI-I) Score
Day 2 (36 hrs)
1.0 score on a scale
Standard Deviation 0.00
Clinical Global Impression-Improvement (CGI-I) Score
Day 3 (48 hrs)
1.3 score on a scale
Standard Deviation 0.50
Clinical Global Impression-Improvement (CGI-I) Score
Day 3 (60 hrs)
1.3 score on a scale
Standard Deviation 0.50
Clinical Global Impression-Improvement (CGI-I) Score
Day 4 (84 hrs)
1.5 score on a scale
Standard Deviation 0.58

Adverse Events

SAGE-547

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
SAGE-547
n=4 participants at risk
Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 micrograms/kg/hr \[4 hrs\], 43 micrograms/kg/hr \[4 hrs\] and 64.5 micrograms/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 micrograms/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 micrograms/kg/hr \[49 - 52 hrs\], 43 micrograms/kg/hr \[53 - 56 hrs\] and 21.5 micrograms/kg/hr \[57 - 60 hrs\] on Day 3).
General disorders
Infusion Site Discomfort
25.0%
1/4 • AEs: Up to Day 11; SAEs: Up to Day 34
Safety population included all participants who began infusion with SAGE-547 injection.
General disorders
Infusion Site Erythema
25.0%
1/4 • AEs: Up to Day 11; SAEs: Up to Day 34
Safety population included all participants who began infusion with SAGE-547 injection.
General disorders
Infusion Site Pain
25.0%
1/4 • AEs: Up to Day 11; SAEs: Up to Day 34
Safety population included all participants who began infusion with SAGE-547 injection.
Investigations
Blood Thyroid Stimulating Hormone Increased
25.0%
1/4 • AEs: Up to Day 11; SAEs: Up to Day 34
Safety population included all participants who began infusion with SAGE-547 injection.
Nervous system disorders
Dizziness
25.0%
1/4 • AEs: Up to Day 11; SAEs: Up to Day 34
Safety population included all participants who began infusion with SAGE-547 injection.
Nervous system disorders
Sedation
50.0%
2/4 • AEs: Up to Day 11; SAEs: Up to Day 34
Safety population included all participants who began infusion with SAGE-547 injection.
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
25.0%
1/4 • AEs: Up to Day 11; SAEs: Up to Day 34
Safety population included all participants who began infusion with SAGE-547 injection.
Skin and subcutaneous tissue disorders
Rash
25.0%
1/4 • AEs: Up to Day 11; SAEs: Up to Day 34
Safety population included all participants who began infusion with SAGE-547 injection.
Vascular disorders
Flushing
25.0%
1/4 • AEs: Up to Day 11; SAEs: Up to Day 34
Safety population included all participants who began infusion with SAGE-547 injection.

Additional Information

Medical Monitor

Sage Therapeutics

Phone: (617) 299-8380

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