Postpartum Depression
Conditions
Keywords
Postpartum depression
Brief summary
This is an open-label proof-of-concept study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of SAGE-547 Injection in adult female participants diagnosed with severe postpartum depression (PPD).
Interventions
DRUGSAGE-547
Intravenous injection
Sponsors
Supernus Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Adult females, 18-45 years old who experienced a major depressive episode in the postpartum period beginning within the first 4 weeks following delivery * Participant has ceased lactating, or if still lactating has already fully and permanently weaned their infant; if still actively breastfeeding, participant must agree to cease giving breast milk to their infant prior to study entry
Exclusion criteria
* Recent history or active clinically significant manifestations of metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, musculoskeletal, dermatological, urogenital, or eyes, ears, or nose and throat (EENT) disorders * Active psychosis * Medical history of seizures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Pre-infusion (Day 1 prior to dosing), Post-infusion (any time after the start of infusion on Day 1 up to 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measure: Specific Gravity | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Vital Sign: Blood Pressure | 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) | 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). |
| Change From Baseline in Vital Sign: Heart Rate | 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) | 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). |
| Change From Baseline in Vital Sign: Body Temperature | 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) | 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). |
| Change From Baseline in Vital Sign: Respiratory Rate | 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) | 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). |
| Change From Baseline in Electrocardiogram (ECG) Parameters: QT Interval, PR Interval, QTc Interval, and QRS Duration | Baseline, Day 4 (at 84 hrs) | ECGs parameters included QT interval, PR interval, QTc interval, QRS duration expressed in terms of milliseconds (msec). |
| Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate | Baseline, Day 4 (at 84 hrs) | ECGs parameter included heart rate expressed in terms of beats per minute (bpm). |
| Number of Participants With Physical Examination Findings | At Day 4 | 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). |
| Number of Participants With Concomitant Medication Usage | Baseline up to Day 11 | 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs: Up to Day 11, TESAEs: Up to Day 34 | 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). |
| Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measure: Hematocrit | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measure: Red Blood Cells (RBC) | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Volume (MCV) | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Hemoglobin (MCH) | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measure: Prothrombin Time/International Normalized Ratio (PT/INR) | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
| Change From Baseline in Clinical Laboratory Measure: Potential of Hydrogen (pH) | Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Plasma Concentration (Tmax) of SAGE-547 | Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose | Tmax is defined as the time at which Cmax of SAGE-547 occurred. |
| Area Under the Concentration-Time Curve From Start of the Infusion Until the Time of the Last Sample (AUCall) of SAGE-547 | Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose | 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. |
| Area Under the Concentration-Time Curve From Time Zero to 60 Hours (AUC0-60) of SAGE-547 | Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, and 60 hrs post-dose | AUC0-60 is defined as the area under the plasma SAGE-547 concentration time curve during the intravenous infusion. |
| Area Under the Concentration-Time Curve in 24 Hours (AUC24) of SAGE-547 | Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, and 24 hrs post-dose | AUC24 is defined as the area under the plasma SAGE-547 concentration-time curve in a 24-hour period during the maintenance dose. |
| Average Drug Concentration in the Plasma at Steady State During a Dosing Interval (Cavg) of SAGE-547 | From 12 to 48 hrs (36 hr of maintenance dose period) | 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). |
| Plasma Clearance (CL) of SAGE-547 | Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose | Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. |
| Change From Baseline in Hamilton Rating Scale for Depression-17 (HAM-D-17) Total Score | 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) | 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. |
| Clinical Global Impression-Improvement (CGI-I) Score | 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) | 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. |
| Maximum Plasma Concentration (Cmax) of SAGE-547 | Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled in the study at 1 center in the United States from 07 January 2015 to 05 June 2015.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| SAGE-547 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). | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | SAGE-547 |
|---|---|
| Age, Continuous | 32.0 years STANDARD_DEVIATION 6.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Change From Baseline in Clinical Laboratory Measure: Hematocrit
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
Primary
Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Hemoglobin (MCH)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
Primary
Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Volume (MCV)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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
Change From Baseline in Clinical Laboratory Measure: Potential of Hydrogen (pH)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
Primary
Change From Baseline in Clinical Laboratory Measure: Prothrombin Time/International Normalized Ratio (PT/INR)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 0.7 |
| SAGE-547 | 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 |
| SAGE-547 | 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
Change From Baseline in Clinical Laboratory Measure: Red Blood Cells (RBC)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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
Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
Primary
Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
Primary
Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 0.1 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
Primary
Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 15.9 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
Primary
Change From Baseline in Clinical Laboratory Measure: Specific Gravity
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | Change From Baseline in Clinical Laboratory Measure: Specific Gravity | Change From Baseline at Day 2 (24 hrs) | -0.0080 ratio | Standard Deviation 0.00458 |
| SAGE-547 | Change From Baseline in Clinical Laboratory Measure: Specific Gravity | Change From Baseline at Day 3 (48 hrs) | -0.0017 ratio | Standard Deviation 0.00252 |
| SAGE-547 | 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
Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 1.91 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 0.1 |
| SAGE-547 | 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 0.1 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 16.5 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
Primary
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate
ECGs parameter included heart rate expressed in terms of beats per minute (bpm).
Time frame: Baseline, Day 4 (at 84 hrs)
Population: Safety population included all participants who began infusion with SAGE-547 injection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAGE-547 | Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate | 14.3 bpm | Standard Deviation 9.29 |
Primary
Change From Baseline in Electrocardiogram (ECG) Parameters: QT Interval, PR Interval, QTc Interval, and QRS Duration
ECGs parameters included QT interval, PR interval, QTc interval, QRS duration expressed in terms of milliseconds (msec).
Time frame: Baseline, Day 4 (at 84 hrs)
Population: Safety population included all participants who began infusion with SAGE-547 injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
Primary
Change From Baseline in Vital Sign: Blood Pressure
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | Change From Baseline in Vital Sign: Blood Pressure | Change From Baseline at Day 3 (48 hrs): Supine SBP | -5.0 mmHg | Standard Deviation 4.4 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | Change From Baseline in Vital Sign: Blood Pressure | Change From Baseline at Day 3(60 hrs):Standing SBP | 16.8 mmHg | Standard Deviation 2.5 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | Change From Baseline in Vital Sign: Blood Pressure | Change From Baseline at Day 1 (12 hrs): Supine DBP | -1.3 mmHg | Standard Deviation 12.5 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
Primary
Change From Baseline in Vital Sign: Body Temperature
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | Change From Baseline in Vital Sign: Body Temperature | Change From Baseline at Day 1 (12 hrs) | -0.20 degree Celsius | Standard Deviation 0.32 |
| SAGE-547 | Change From Baseline in Vital Sign: Body Temperature | Change From Baseline at Day 2 (24 hrs) | 0.15 degree Celsius | Standard Deviation 0.23 |
| SAGE-547 | Change From Baseline in Vital Sign: Body Temperature | Change From Baseline at Day 2 (36 hrs) | -0.15 degree Celsius | Standard Deviation 0.33 |
| SAGE-547 | Change From Baseline in Vital Sign: Body Temperature | Change From Baseline at Day 3 (48 hrs) | -0.05 degree Celsius | Standard Deviation 0.25 |
| SAGE-547 | Change From Baseline in Vital Sign: Body Temperature | Change From Baseline at Day 3 (60 hrs) | 0.03 degree Celsius | Standard Deviation 0.31 |
| SAGE-547 | Change From Baseline in Vital Sign: Body Temperature | Change From Baseline at Day 4 (72 hrs) | -0.30 degree Celsius | Standard Deviation 0.37 |
| SAGE-547 | 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
Change From Baseline in Vital Sign: Heart Rate
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | Change From Baseline in Vital Sign: Heart Rate | Change From Baseline at Day 1 (12 hrs) | -2.5 bpm | Standard Deviation 15.35 |
| SAGE-547 | Change From Baseline in Vital Sign: Heart Rate | Change From Baseline at Day 2 (24 hrs) | 5.3 bpm | Standard Deviation 18.84 |
| SAGE-547 | Change From Baseline in Vital Sign: Heart Rate | Change From Baseline at Day 2 (36 hrs) | -2.3 bpm | Standard Deviation 11.44 |
| SAGE-547 | Change From Baseline in Vital Sign: Heart Rate | Change From Baseline at Day 3 (48 hrs) | -1.5 bpm | Standard Deviation 11.56 |
| SAGE-547 | Change From Baseline in Vital Sign: Heart Rate | Change From Baseline at Day 3 (60 hrs) | -3.0 bpm | Standard Deviation 8.41 |
| SAGE-547 | Change From Baseline in Vital Sign: Heart Rate | Change From Baseline at Day 4 (72 hrs) | -5.8 bpm | Standard Deviation 7.63 |
| SAGE-547 | Change From Baseline in Vital Sign: Heart Rate | Change From Baseline at Day 4 (84 hrs) | -0.8 bpm | Standard Deviation 4.99 |
Primary
Change From Baseline in Vital Sign: Respiratory Rate
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | Change From Baseline in Vital Sign: Respiratory Rate | Change From Baseline at Day 1 (12 hrs) | 0.0 breaths/min | Standard Deviation 1.63 |
| SAGE-547 | Change From Baseline in Vital Sign: Respiratory Rate | Change From Baseline at Day 2 (24 hrs) | 0.0 breaths/min | Standard Deviation 2.31 |
| SAGE-547 | Change From Baseline in Vital Sign: Respiratory Rate | Change From Baseline at Day 2 (36 hrs) | 0.0 breaths/min | Standard Deviation 2.31 |
| SAGE-547 | Change From Baseline in Vital Sign: Respiratory Rate | Change From Baseline at Day 3 (48 hrs) | 0.0 breaths/min | Standard Deviation 4 |
| SAGE-547 | Change From Baseline in Vital Sign: Respiratory Rate | Change From Baseline at Day 3 (60 hrs) | 0.3 breaths/min | Standard Deviation 1.53 |
| SAGE-547 | Change From Baseline in Vital Sign: Respiratory Rate | Change From Baseline at Day 4 (72 hrs) | -1.0 breaths/min | Standard Deviation 1.15 |
| SAGE-547 | Change From Baseline in Vital Sign: Respiratory Rate | Change From Baseline at Day 4 (84 hrs) | -0.5 breaths/min | Standard Deviation 1 |
Primary
Number of Participants With Concomitant Medication Usage
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.
Time frame: Baseline up to Day 11
Population: Safety population included all participants who began infusion with SAGE-547 injection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAGE-547 | Number of Participants With Concomitant Medication Usage | 3 Participants |
Primary
Number of Participants With Physical Examination Findings
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).
Time frame: At Day 4
Population: Safety population included all participants who began infusion with SAGE-547 injection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAGE-547 | Number of Participants With Physical Examination Findings | 4 Participants |
Primary
Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
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).
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAGE-547 | Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Pre-Infusion: Suicidal Ideation | 3 Participants |
| SAGE-547 | Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Post-Infusion: Suicidal Ideation | 0 Participants |
| SAGE-547 | Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Pre-Infusion: Suicidal Behavior | 1 Participants |
| SAGE-547 | Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Post-Infusion: Suicidal Behavior | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
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).
Time frame: TEAEs: Up to Day 11, TESAEs: Up to Day 34
Population: Safety population included all participants who began infusion with SAGE-547 injection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAGE-547 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 Participants |
| SAGE-547 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
Secondary
Area Under the Concentration-Time Curve From Start of the Infusion Until the Time of the Last Sample (AUCall) of SAGE-547
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAGE-547 | 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
Area Under the Concentration-Time Curve From Time Zero to 60 Hours (AUC0-60) of SAGE-547
AUC0-60 is defined as the area under the plasma SAGE-547 concentration time curve during the intravenous infusion.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAGE-547 | 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
Area Under the Concentration-Time Curve in 24 Hours (AUC24) of SAGE-547
AUC24 is defined as the area under the plasma SAGE-547 concentration-time curve in a 24-hour period during the maintenance dose.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAGE-547 | Area Under the Concentration-Time Curve in 24 Hours (AUC24) of SAGE-547 | 1590 ng*hr/mL | Standard Deviation 580 |
Secondary
Average Drug Concentration in the Plasma at Steady State During a Dosing Interval (Cavg) of SAGE-547
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).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAGE-547 | 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
Change From Baseline in Hamilton Rating Scale for Depression-17 (HAM-D-17) Total Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 |
| SAGE-547 | 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 5.5 |
| SAGE-547 | 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
Clinical Global Impression-Improvement (CGI-I) Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-547 | Clinical Global Impression-Improvement (CGI-I) Score | Day 1 (12 hrs) | 1.8 score on a scale | Standard Deviation 0.5 |
| SAGE-547 | Clinical Global Impression-Improvement (CGI-I) Score | Day 3 (60 hrs) | 1.3 score on a scale | Standard Deviation 0.5 |
| SAGE-547 | Clinical Global Impression-Improvement (CGI-I) Score | Day 4 (84 hrs) | 1.5 score on a scale | Standard Deviation 0.58 |
| SAGE-547 | Clinical Global Impression-Improvement (CGI-I) Score | Day 2 (24 hrs) | 1.3 score on a scale | Standard Deviation 0.5 |
| SAGE-547 | Clinical Global Impression-Improvement (CGI-I) Score | Day 2 (36 hrs) | 1.0 score on a scale | Standard Deviation 0 |
| SAGE-547 | Clinical Global Impression-Improvement (CGI-I) Score | Day 3 (48 hrs) | 1.3 score on a scale | Standard Deviation 0.5 |
Secondary
Maximum Plasma Concentration (Cmax) of SAGE-547
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAGE-547 | Maximum Plasma Concentration (Cmax) of SAGE-547 | 97.2 nanograms per millilter (ng/mL) | Standard Deviation 77.3 |
Secondary
Plasma Clearance (CL) of SAGE-547
Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAGE-547 | Plasma Clearance (CL) of SAGE-547 | 1.08 Liters per hour per kilogram (L/hr/kg) | Standard Deviation 0.22 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of SAGE-547
Tmax is defined as the time at which Cmax of SAGE-547 occurred.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SAGE-547 | Time to Maximum Plasma Concentration (Tmax) of SAGE-547 | 42 hours |