Recent Updates
Recently added Catalysts

SAGE-217

Phase 3

Depression, Postpartum | Small molecule | Psychiatry |Biogen Inc.|Last Updated: Aug 27, 2024

Success Probability

Subscribe to view

Market & Valuation

Subscribe to view

Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment200

FDA Designations

No designations recorded

Clinical trial landscape

SAGE-217 · 9 trials · 9 indications

Phase 3 5Phase 2 4
NCT04476030A Comparative Study of Sage-217 Plus an Antidepressant (ADT) Versus Placebo Plus an ADT in Adults With Major Depressive DisorderDepressive Disorder, Major
COMPLETED440 Analytics
NCT04442503A Study to Evaluate the Efficacy and Safety of SAGE-217 in Participants With Severe Postpartum Depression (PPD)Depression, Postpartum
COMPLETED200 Analytics
NCT04442490A Study to Evaluate the Efficacy of Sage-217 in the Treatment of Adult Participants With Major Depressive Disorder (MDD)Depressive Disorder, Major
COMPLETED543 Analytics
NCT03864614A Study to Evaluate SAGE-217 in Adult Participants With Major Depressive Disorder (MDD)Major Depressive Disorder
COMPLETED1,515 Analytics
NCT03672175A Study to Evaluate the Efficacy of SAGE-217 in the Treatment of Adult Participants With Major Depressive DisorderMajor Depressive Disorder
COMPLETED581 Analytics
PHASE3COMPLETED
A Comparative Study of Sage-217 Plus an Antidepressant (ADT) Versus Placebo Plus an ADT in Adults With Major Depressive Disorder
Depressive Disorder, MajorUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate the Efficacy and Safety of SAGE-217 in Participants With Severe Postpartum Depression (PPD)
Depression, PostpartumUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate the Efficacy of Sage-217 in the Treatment of Adult Participants With Major Depressive Disorder (MDD)
Depressive Disorder, MajorUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate SAGE-217 in Adult Participants With Major Depressive Disorder (MDD)
Major Depressive DisorderUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate the Efficacy of SAGE-217 in the Treatment of Adult Participants With Major Depressive Disorder
Major Depressive DisorderUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline in the HAMD-17 Total Score at Day 3
Baseline, Day 3

The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. A negative change from baseline indicated improvement. Least Squares (LS) mean was estimated using mixed effects model for repeated measures (MMRM) analysis.

Change From Baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15
Baseline and Day 15

The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of 17 individual items related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), retardation, agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of the 17 individual items, ranges from 0 to 52; where a higher score indicates more depression. Negative change from baseline indicates improvement. Mixed Model for Repeated Measures (MMRM) was used for the analysis.

Change From Baseline in the 17-item HAM-D Total Score at Day 15
Baseline, Day 15

The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total HAM-D score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression. A negative change indicates improvement. A mixed Model for Repeated Measures (MMRM)was used for the analysis.

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Up to 52 Weeks

An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. For Part A, a TEAE was defined as an AE with onset after the first dose of SAGE-217.

Part B: Number of Participants With TEAEs
Up to 46 Weeks

An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. For Part B, a TEAE was defined as an AE with onset on or after the first dose of SAGE-217 in MDD-303B for the participants who received placebo + ADT in parent study, or an AE with onset on or after the ICF signoff in MDD-303B for the participants who received SAGE-217 + ADT in parent study.

Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Baseline up to 52 Weeks (Study Period 1-5)

C-SSRS scale consisted of a baseline evaluation that assessed lifetime experience as well as past 24-month experience of participants for SI and SB and a postbaseline evaluation that focused on suicidality since last study visit. C-SSRS included "yes" or "no"' responses for assessment of SI and SB as well as numeric ratings for severity of ideation, if present. The C-SSRS SI items included: 1. wish to be dead, 2. non-specific active suicidal thoughts, 3. active SI with any methods, 4. active SI with some intent, and 5. active SI with a specific plan (5 being the most severe). C-SSRS SB items included 1. preparatory acts or behavior, 2. aborted attempt, 3. interrupted attempt, 4. actual attempt (non-fatal), and 5. completed suicide (5 being worst). Participants with at least one SI question answered Yes or at least one SB question answered Yes post-baseline for the specific period is counted under SI or SB respectively.

Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS
Baseline up to 46 Weeks (Study Period 1-5)

C-SSRS scale consisted of a baseline evaluation that assessed lifetime experience as well as past 24-month experience of participants for SI and SB and a postbaseline (PB) evaluation that focused on suicidality since last study visit. C-SSRS included "yes" or "no"' responses for assessment of SI and SB as well as numeric ratings for severity of ideation, if present. The C-SSRS SI items included: 1. wish to be dead, 2. non-specific active suicidal thoughts, 3. active SI with any methods, 4. active SI with some intent, and 5. active SI with a specific plan (5 being the most severe). C-SSRS SB items included 1. preparatory acts or behavior, 2. aborted attempt, 3. interrupted attempt, 4. actual attempt (non-fatal), and 5. completed suicide (5 being worst). Participants with at least one SI question answered Yes or at least one SB question answered Yes post-baseline for the specific period is counted under SI or SB respectively.

Part A: Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs)
From first dose of study drug up to Day 42

An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE was defined as an adverse event with onset after the start of study through Day 42/early termination.

Part A: Number of Participants With TEAEs, Graded by Severity
From first dose of study drug up to Day 42

An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE was defined as an adverse event with onset after the start of study through Day 42/early termination. Severity was assessed according to the following scale: mild (awareness of sign or symptom, but easily tolerated); moderate (discomfort sufficient to cause interference with normal activities); severe (incapacitating, with inability to perform normal activities).

Part A: Percentages of Participants With Response to Suicidal Ideation and Suicidal Behavior Based on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Baseline, Post-baseline (any time up to Day 42)

Suicidality was monitored using the C-SSRS. This 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 (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal), completed suicide). Percentage of participants with response 'yes' are reported for both suicidal ideation and behavior.

Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Baseline, Days 3, 8, 12, 15, 21, 28, 35, and 42, Last value on treatment (up to Day 14), Last value on study (up to Day 42)

Manic symptoms were assessed during the study using the YMRS. The clinician-administered scale is based on 11 items of core symptoms of mania. Four of the items (irritability, speech, thought content, and disruptive/aggressive behavior) were graded on a scale of 0 to 8 (choices given as even numbers), with the remaining 7 items graded on a scale of 0 to 4. Scoring between the points given (whole or half points) is possible. The YMRS total score ranges from 0 (no symptoms) to 60 (extreme severity of symptoms). A higher total score indicates a greater degree of mania. A negative change indicates better state of health.

Part B: Change From Baseline in the 17-Item Hamilton Depression Rating Scale (HAM-D) Total Score
Baseline up to Day 42

The 17-item HAM-D was used to rate the severity of depression in participants who were identified as experiencing a major depressive episode (MDE). 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. Items scored in a range of 0 to 4 include: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score was calculated as the sum of the 17 individual item scores, with a range of 0 (not at all depressed) to 52 (severely depressed). Higher scores indicated more depression. A negative change from baseline indicates improvement.

Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7
Baseline (Day 1) and Day 7 (8 hours postdose)

The accelerometer-based Kinesia kinetic tremor combined score is the sum of Kinesia kinetic tremor scores across both sides of the body. Tremor is measured using a motion sensor that transmits raw data to a computer where it converts the tremor amplitude to a Kinesia score of 0 to 4 based on validated algorithms; the total score ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.

Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14
Randomization (Day 8, predose) and Day 14 (predose)

The accelerometer-based Kinesia kinetic tremor combined score is the sum of Kinesia kinetic tremor scores across both sides of the body. Tremor is measured using a motion sensor that transmits raw data to a computer where it converts the tremor amplitude to a Kinesia score of 0 to 4 based on validated algorithms; the total score ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement.

Part C: Change From Baseline in the Accelerometer-based Kinesia Upper Limb Tremor Combined Score at Day 15
Baseline (Day 1) and Day 15

The accelerometer-based Kinesia upper limb total score is the sum of the individual item scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral "wing beating" postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement.

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) - Part A
Day 1 up to Day 21

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as an adverse event with onset after the start of study drug, or any worsening of a pre-existing medical condition/adverse event with onset after the start of study drug and until 7 days after the last dose. The analysis was performed in participants included in Part A of the study.

Percentage of Participants With TEAEs, Graded by Severity - Part A
Day 1 up to Day 21

Severity was assessed according to the following scale: mild (awareness of sign or symptom, but easily tolerated); moderate (discomfort sufficient to cause interference with normal activities); severe (incapacitating, with inability to perform normal activities). The analysis was performed in participants included in Part A of the study.

Change From Baseline in Basophils - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Basophils to Leukocytes Ratio [Percentage (%)] - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as International System (SI) unit, percentage (%).

Change From Baseline in Eosinophils - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Change From Baseline in Hematocrit - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Hemoglobin - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Lymphocytes - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Change From Baseline in Monocytes - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Change From Baseline in Neutrophils - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Change From Baseline in Platelets - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Erythrocytes - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Reticulocytes - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Leukocytes - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Albumin - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Alkaline Phosphatase - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Alanine Aminotransferase - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Aspartate Aminotransferase - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Bilirubin - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Chloride - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Carbon Dioxide - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Creatinine - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Potassium - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Protein - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Sodium - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Urea Nitrogen - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Activated Partial Thromboplastin Time - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio, and prothrombin time. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Prothrombin International Normalized Ratio (%) - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio, and prothrombin time. The analysis was performed in participants included in Part A of the study. ET = Early Termination. The data for prothrombin international normalized ratio are presented as SI unit, percentage (%).

Change From Baseline in Prothrombin Time - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio, and prothrombin time. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in pH - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline in Specific Gravity - Part A
Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A
Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Days 8, 9, 10, 11, 12, 13 and 14 (predose, 1 hour postdose), Day 15/ET, follow-up Day 21, follow-up Day 28

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part A of the study. H = Hour(s). ET = Early Termination.

Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A
Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Days 8, 9, 10, 11, 12, 13 and 14 (predose, 1 hour postdose), Day 15/ET, follow-up Day 21, follow-up Day 28

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part A of the study. H = Hour(s). ET = Early Termination.

Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A
Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Days 8, 9, 10, 11, 12, 13 and 14 (predose, 1 hour postdose), Day 15/ET, follow-up Day 21, follow-up Day 28

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part A of the study. H = Hour(s). ET = Early Termination.

Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A
Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Days 8, 9, 10, 11, 12, 13 and 14 (predose, 1 hour postdose), Day 15/ET, follow-up Day 21, follow-up Day 28

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part A of the study. H = Hour(s). ET = Early Termination.

Change From Baseline (CFB) in Heart Rate - Part A
Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Days 8, 9, 10, 11, 12, 13 and 14 (predose, 1 hour postdose), Day 15/ET, follow-up Day 21, follow-up Day 28

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part A of the study. H = Hour(s). ET = Early Termination.

Change From Baseline (CFB) in Respiratory Rate - Part A
Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Days 8, 9, 10, 11, 12, 13 and 14 (predose, 1 hour postdose), Day 15/ET, follow-up Day 21, follow-up Day 28

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part A of the study. H = Hour(s). ET = Early Termination.

Change From Baseline (CFB) in Oral Temperature - Part A
Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Days 8, 9, 10, 11, 12, 13 and 14 (predose, 1 hour postdose), Day 15/ET, follow-up Day 21, follow-up Day 28

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part A of the study. H = Hour(s). ET = Early Termination.

Change From Baseline (CFB) in Oxygen Saturation - Part A
Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Day 8 (predose, 1 hour postdose)

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part A of the study. H = Hour(s).

Change From Baseline in QT Interval - Part A
Baseline, Days 1, 2, 7, 14 and follow-up Day 21

Electrocardiogram (ECG) measures included QT interval, QTc based on Fridericia formula (QTcF interval), ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Change From Baseline in QTcF Interval - Part A
Baseline, Days 1, 2, 7, 14 and follow-up Day 21

ECG measures included QT interval, QTcF interval, ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Change From Baseline in ECG Mean Heart Rate - Part A
Baseline, Days 1, 2, 7, 14 and follow-up Day 21

ECG measures included QT interval, QTcF interval, ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Change From Baseline in RR Interval - Part A
Baseline, Days 1, 2, 7, 14 and follow-up Day 21

ECG measures included QT interval, QTcF interval, ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Change From Baseline in PR Interval - Part A
Baseline, Days 1, 2, 7, 14 and follow-up Day 21

ECG measures included QT interval, QTcF interval, ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Change From Baseline in QRS Interval - Part A
Baseline, Days 1, 2, 7, 14 and follow-up Day 21

ECG measures included QT interval, QTcF interval, ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item - Part A
Day 1 up to Day 28

The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and behavior and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included "yes" or "no"' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with specific plan. The analysis was performed in participants included in Part A of the study.

Change From Baseline in Stanford Sleepiness Scale (SSS) Score at Day 15 - Part A
Baseline, Day 15

The SSS was participant-rated scale designed to quickly assess how alert a participant was feeling. Degrees of sleepiness and alertness were rated on a scale of one to seven, where the lowest score of 'one' indicated the participant was 'feeling active, vital, alert, or wide awake' and the highest score of 'seven' indicated the participant was 'no longer fighting sleep, sleep onset soon; having dream-like thoughts'. A negative change from baseline indicated less sleepiness. A positive change from baseline indicated more sleepiness. The analysis was performed in participants included in Part A of the study.

Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 - Part B
Baseline, Day 15

The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items were scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The total score could range from 0 to 52. Higher scores indicated a greater degree of depression. A negative change from baseline indicated less depression. A positive change from baseline indicated more depression. The analysis was performed in participants included in Part B of the study.

Change From Baseline (CFB) in Basophils - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Basophils to Leukocytes Ratio [Percentage (%)] - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as International System (SI) unit, percentage (%).

CFB in Eosinophils - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Eosinophils to Leukocytes Ratio (%) - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

CFB in Erythrocytes - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Hematocrit - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Hemoglobin - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Leukocytes - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Lymphocytes - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Lymphocytes to Leukocytes Ratio (%) - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

CFB in Monocytes - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Monocytes to Leukocytes Ratio (%) - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

CFB in Neutrophils- Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Neutrophils to Leukocytes Ratio (%) - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

CFB in Platelets - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Reticulocytes - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Reticulocytes to Erythrocytes Ratio (%) - Part A
Day 1 to Day 14

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

CFB in Activated Partial Thromboplastin Time - Part A
Day 1 to Day 14

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio and prothrombin time. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Prothrombin International Normalized Ratio - Part A
Day 1 to Day 14

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio and prothrombin time. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Prothrombin Time - Part A
Day 1 to Day 14

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio and prothrombin time. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Alanine Aminotransferase - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Albumin - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Alkaline Phosphatase - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Aspartate Aminotransferase - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Bicarbonate - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Bilirubin - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Calcium - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Chloride - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Creatinine - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Lipase - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Magnesium - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Phosphate - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Potassium - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Protein - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Sodium - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Urate - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Urea Nitrogen - Part A
Day 1 to Day 14

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

CFB in Specific Gravity - Part A
Day 1 to Day 14

Urinalysis measures included specific gravity and potential of hydrogen (pH). Baseline is the last measurement taken before the first dose of study drug. The analysis was performed in participants included in Part A of the study.

CFB in pH - Part A
Day 1 to Day 14

Urinalysis measures included specific gravity and pH. Baseline is the last measurement taken before the first dose of study drug. The analysis was performed in participants included in Part A of the study.

CFB in Temperature - Part A
Day 1 to Day 14

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Heart Rate - Part A
Day 1 to Day 14

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Respiratory Rate - Part A
Day 1 to Day 14

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Supine Systolic Blood Pressure - Part A
Day 1 to Day 14

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Standing Systolic Blood Pressure - Part A
Day 1 to Day 14

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Supine Diastolic Blood Pressure - Part A
Day 1 to Day 14

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Standing Diastolic Blood Pressure - Part A
Day 1 to Day 14

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Pulse Oximetry- Part A
Day 1 to Day 14

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A
Day 1 to Day 14

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Aggregate PR Interval - Part A
Day 1 to Day 14

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Aggregate RR Interval - Part A
Day 1 to Day 14

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Aggregate QT Interval - Part A
Day 1 to Day 14

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Aggregate QRS Duration - Part A
Day 1 to Day 14

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Aggregate QTcF Interval - Part A
Day 1 to Day 14

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

CFB in Stanford Sleepiness Scale (SSS) Score - Part A
Day 1 to Day 14

The SSS was a participant-rated scale designed to quickly assess how alert a participant was feeling. Degrees of sleepiness and alertness were rated on a scale of one to seven, where the lowest score of 'one' indicated the participant was 'feeling active, vital, alert, or wide awake' and the highest score of 'seven' indicated the participant was 'no longer fighting sleep, sleep onset soon; having dream-like thoughts'. A negative change from baseline indicated less sleepiness. A positive change from baseline indicated more sleepiness. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item - Part A
Day 1 to Day 14

The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included "yes" or "no"' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with a specific plan. The C-SSRS SB items involved actual attempt, interrupted attempt, aborted attempt, preparatory acts or behavior, suicidal behavior and suicide. The analysis was performed in participants included in Part A of the study.

CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B
Baseline, Days 1 to 6 (12 and 23 hours postdose), Day 7 (12 hours postdose), Day 14

The modified MDS-UPDRS included 4 scales, with various subscales. Each item was rated from 0 (normal) to 4 (severe). The scales were Part I: nonmotor experiences of daily living (13 items); Part II: motor experiences of daily living (13 items); Part III: motor examination (33 scores based on 18 items \[several with right, left or other body distribution scores\]); and Part IV: motor complications (6 items). The Part II/III tremor score was calculated as the sum of 5 individual tremor item scores from Part II and Part III. The total score range for Part II/III is 0 to 44. Lower scores represent less symptom severity and higher scores represent more symptom severity. Baseline is the last measurement taken before the first dose of study drug. A negative change from baseline indicates an improvement in symptom severity. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Secondary Endpoints

Change From Baseline in the HAMD-17 Total Score Over the Double-Blind Treatment Period
Baseline through Day 15
Change From Baseline in the HAMD-17 Total Score at Days 15 and 42
Baseline, Days 15 and 42
Change From Baseline in the HAMD-17 Total Score Around End of Blinded Treatment
Baseline, End of blinded treatment assessment (i.e., average of Days 12, 15 , and 18)
Unlock Study Endpoints

Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Placebo + Assigned ADTACTIVE_COMPARATORParticipants received SAGE-217-matching placebo capsules, orally, once daily along with an assigned ADT (sertraline, escitalopram, citalopram, duloxetine, or desvenlafaxine administered per labeled prescribing information), daily, from Day 1 through 14, followed by the same ADT, per labeled prescribing information, daily, up to Day 42.
SAGE-217 + Assigned ADTEXPERIMENTALParticipants received SAGE-217, 50 milligrams (mg), orally, once daily along with an assigned ADT (sertraline, escitalopram, citalopram, duloxetine, or desvenlafaxine administered per labeled prescribing information), daily from Day 1 through 14, followed by the same ADT, per labeled prescribing information, daily, up to Day 42.
PlaceboPLACEBO_COMPARATORParticipants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
SAGE-217 50 mgEXPERIMENTALParticipants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
SAGE-217EXPERIMENTAL -
SAGE-217 Matched PlaceboPLACEBO_COMPARATORParticipants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.
SAGE-217 20 mgEXPERIMENTALParticipants self-administered SAGE-217 20 milligrams (mg) capsules, orally, once daily in the evening with food for 14 days.
SAGE-217 30 mgEXPERIMENTALParticipants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.
Part A (Open-label): SAGE-217EXPERIMENTALParticipants self-administered SAGE-217, 30 milligrams (mg), oral capsule, once daily (QD), in the evening, from Day 1 to Day 14.
Part B (Double-blind): SAGE-217EXPERIMENTALParticipants were to receive SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
Part B (Double-blind): PlaceboPLACEBO_COMPARATORParticipants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
Part A: SAGE-217 Oral SolutionEXPERIMENTALParticipants received SAGE-217 10 mg oral solution on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 with food in the morning.
Part A: SAGE-217 CapsulesEXPERIMENTALParticipants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.
Part B: PlaceboPLACEBO_COMPARATORParticipants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.
Part B: SAGE-217 CapsulesEXPERIMENTALParticipants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.
Part C: SAGE-217 CapsulesEXPERIMENTALParticipants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).
Part A: SAGE-217EXPERIMENTALParticipants received SAGE-217, 30 milligrams (mg), oral solution, once daily for 14 days, as tolerated.
Part B: SAGE-217EXPERIMENTALEligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Part A: Antiparkinsonian Agent(s) Followed by SAGE-217EXPERIMENTALParticipants on a stable morning dose of levodopa (including carbidopa-levodopa) as antiparkinsonian agent(s) from Days 1 to 3, stopped levodopa and received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. Stable doses of other antiparkinsonian agents and dose reductions in SAGE-217 were allowed between Days 1 to 7. Participants resumed stable morning dose of levodopa from Days 8 to 14.
Part B: Antiparkinsonian Agent(s) + SAGE-217EXPERIMENTALParticipants on a stable dose of antiparkinsonian agent(s) received SAGE-217, up to 30 mg per day, capsules, for Days 1 to 7 in the evening with food.

Interventions

NameTypeDescription
SAGE-217DRUGOral capsules
Matching PlaceboDRUGOral capsules
SertralineDRUGOral tablets
EscitalopramDRUGOral tablets
CitalopramDRUGOral tablets
DuloxetineDRUGOral capsules
DesvenlafaxineDRUGOral tablets
PlaceboDRUGSAGE-217 matched-placebo oral capsules.
LevodopaDRUGLevodopa (including carbidopa-levodopa) administered as antiparkinsonian agent(s).
Antiparkinsonian Agent(s)DRUGAntiparkinsonian agent(s) were administered as a clinical practice as standard of care, which includes levodopa (i.e. levodopa/carbidopa) or dopamine agonists or catechol-O-methyltransferase (COMT) inhibitors or monoamine oxidase (BMAO-B) inhibitors.
Unlock Study Design Details

Eligibility Criteria

Age Range18 Years to 64 Years
SexALL
Healthy VolunteersNo
Study Sites51

Inclusion Criteria: * Diagnosis of MDD as diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Clinical Trials Version (SCID-5-CT), with symptoms that have been present for at least a 4-week period * 17-item Hamilton Rating Scale for De...

Countries:United StatesSpainUnited Kingdom
Unlock Eligibility Criteria

Frequently asked questions about SAGE-217

What is SAGE-217 used for?

SAGE-217 is an investigational small molecule being developed for psychiatric conditions, including major depressive disorder, bipolar I disorder, and major depression. It has also been studied in essential tremor and Parkinson disease. The drug is not approved and remains in clinical development.

Who makes SAGE-217?

SAGE-217 is being developed by Biogen Inc., a biopharmaceutical company traded on the NASDAQ under the ticker BIIB. The drug is an investigational small molecule in the psychiatry therapeutic area.

What phase is SAGE-217 in?

SAGE-217 is in Phase 3 clinical development for major depressive disorder. It is an investigational drug and has not been approved by regulatory authorities. Completed trials include Phase 3 studies in adult participants with major depressive disorder.

What clinical trials is SAGE-217 in?

SAGE-217 has completed four Phase 3 trials in major depressive disorder: NCT03672175 with 581 participants, NCT03864614 with 1515 participants, NCT04442490 with 543 participants, and NCT04476030 with 440 participants. All trials were conducted in the United States and were placebo-controlled.

Is SAGE-217 the same as zuranolone?

SAGE-217 is also known as zuranolone. It is an investigational small molecule being developed by Biogen Inc. for psychiatric conditions including major depressive disorder. The drug has been studied in Phase 3 clinical trials.