Major Depressive Disorder
Conditions
Brief summary
This is a Phase 3, open-label, 1-year study of the safety, tolerability, and need for re-treatment with SAGE-217 in adult participants with MDD.
Detailed description
This study was previously posted by Sage Therapeutics. In July 2024, sponsorship of the trial was transferred to Biogen.
Interventions
DRUGSAGE-217
SAGE-217
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Participant has a diagnosis of MDD as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Clinical Trial Version (SCID-5-CT), with symptoms that have been present for at least a 4-week period. 2. Participant is in good physical health and has no clinically significant findings, as determined by the Investigator, on physical examination, 12-lead electrocardiogram (ECG), or clinical laboratory tests. 3. Participant has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of ≥28 and a HAM-D total score of ≥20 at Screening and Day 1 (prior to dosing).
Exclusion criteria
1. Participant has attempted suicide associated with the current episode of MDD. 2. Participant has a medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder. 3. Participant has had vagus nerve stimulation, electroconvulsive therapy, or has taken ketamine (including esketamine) within the current major depressive episode.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Baseline, Day 15 of treatment cycles 2, 3, 4, and 5 | The 17-item HAM-D scale was used for measuring severity of depression. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Each item is scored in a range of 0 to 2 or 0 to 4. The total score ranges from 0 to 52 with higher scores indicating a greater degree of depression. A negative change from baseline indicates improvement. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. |
| Part B: Change From Baseline in the HAMD-17 Total Score at Day 15 of Each Treatment (Initial and/or Repeat Treatment) Cycle | Baseline, Day 15 of Study Period 1, 2, 3, 4, and 5 | The 17-item HAM-D scale was used to measure the severity of depression. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Each item is scored in a range of 0 to 2 or 0 to 4. The total score ranges from 0 to 52 with higher scores indicating a greater degree of depression. A negative change from baseline indicates improvement. Study period is defined as treatment cycle (28 days) followed by immediate observation period (maximum 46 weeks), until the first dose of the subsequent treatment cycle. |
| Part A: Percentage of Participants Who Achieved HAM-D Response During Treatment Cycle 1 | Day 15 of treatment cycle 1 | HAM-D response was defined as a ≥50% reduction in HAM-D score from baseline, at the end of each 14-day treatment period. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. Percentage are rounded off. |
| Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Day 15 of Study Period 2, 3, 4, and 5 | HAM-D response was defined as a ≥50% reduction in HAM-D score from baseline, at the end of each 14-day treatment period. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. A study period is a treatment cycle (treatment period+14-day follow-up) plus the observational period (until next treatment cycle or end of study, whichever is earlier) immediately following it. Percentage are rounded off. |
| Part B: Percentage of Participants Who Achieved HAM-D Response | Day 15 of Study Period 1, 2, 3, 4, and 5 | HAM-D response was defined as a ≥50% reduction in HAM-D score from baseline, at the end of each 14-day treatment period. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. A study period is defined as treatment cycle (28 days) followed by immediate observation period (maximum 46 weeks), until the first dose of the subsequent treatment cycle. Percentage are rounded off. |
| Part A: Percentage of Participants Who Achieved HAM-D Remission During Treatment Cycle 1 | Day 15 of treatment cycle 1 | Remission was defined as having a HAM-D total score of ≤7. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. Percentage are rounded off. |
| Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Day 15 of Study Periods 2, 3, 4, and 5 | Remission was defined as having a HAM-D total score of ≤7. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. A study period is a treatment cycle (treatment period+14-day follow-up) plus the observational period (until next treatment cycle or end of study, whichever is earlier) immediately following it. Percentage are rounded off. |
| Parts A and B: Time to First Repeat Treatment With SAGE-217 | Up to 52 Weeks | For Part A, the first day of the first repeat treatment is Treatment Cycle 2 Day 1. For Part B, participants who had placebo + ADT in the parent study (217-MDD-305), the first repeat treatment of SAGE-217 was the second treatment within MDD-303B. Participants who had SAGE-217 + ADT in the parent study (217-MDD-305), the first repeat treatment of SAGE-217 was the first treatment within MDD-303B. For Part A, as prespecified, data for this outcome measure was collected for Sage-217 High-dose Cohort and Sage-217 30 mg Cohort (Low Dose + Dose Switch). For Part B, data for this outcome measure is presented as per the designated arms in the parent study (217-MDD-305). Analysis used Kaplan-Meier estimates where the participants with no repeat treatment were censored. |
| Part A: Percentage of Participants Who Achieved Clinical Global Impression - Improvement (CGI-I) Response During Treatment Cycle 1 | Day 15 of treatment cycle 1 | The CGI scale consists of 3 items. Only the first 2 items are being used in this study. The CGI-I employed a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement compared to baseline, whether or not it was due entirely to drug treatment. Response choices included: 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The CGI-I is only rated at posttreatment assessments. CGI-I response was defined as having a CGI-I score of very much improved or much improved. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. Percentage are rounded off. |
| Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Day 15 of Study Periods 2, 3, 4, and 5 | The CGI scale consists of 3 items. Only the first 2 items are being used in this study. The CGI-I employed a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement compared to baseline, whether or not it was due entirely to drug treatment. Response choices included: 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The CGI-I is only rated at posttreatment assessments. CGI-I response was defined as having a CGI-I score of very much improved or much improved. A study period is a treatment cycle (treatment period+14-day follow-up) plus the observational period (until next treatment cycle or end of study, whichever is earlier) immediately following it. Percentage are rounded off. |
| Part B: Percentage of Participants Who Achieved CGI-I Response | Day 15 of Study Period 1, 2, 3, 4, and 5 | The CGI scale consists of 3 items. Only the first 2 items are being used in this study. The CGI-I employed a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement compared to baseline, whether or not it was due entirely to drug treatment. Response choices included: 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The CGI-I is only rated at posttreatment assessments. CGI-I response was defined as having a CGI-I score of very much improved or much improved. A Study Period is defined as Treatment Cycle (28 days) followed by the immediate observational period (maximum 46 weeks), until the first dose of the subsequent treatment cycle. Percentage are rounded off. |
| Part A: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score During Treatment Cycle 1 | Baseline, Day 15 of treatment cycle 1 | The CGI-S uses a 7-point Likert scale to rate the severity of the participant's mental illness at the time of assessment, relative to the clinician's past experience with participants who had the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=extremely ill. A higher score indicated extreme illness. A negative change from baseline indicated improvement. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. |
| Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Baseline, Day 15 of treatment cycles 2, 3, 4, and 5 | The CGI-S uses a 7-point Likert scale to rate the severity of the participant's mental illness at the time of assessment, relative to the clinician's past experience with participants who had the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=extremely ill. A higher score indicated extreme illness. A negative change from baseline indicated improvement. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. |
| Part B: Change From Baseline in CGI-S Score | Baseline Day 15 of Study Period 1, 2, 3, 4, and 5 | The CGI-S uses a 7-point Likert scale to rate the severity of the participant's mental illness at the time of assessment, relative to the clinician's past experience with participants who had the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=extremely ill. A higher score indicated extreme illness. A negative change from baseline indicated improvement. A Study Period is defined as Treatment Cycle (28 days) followed by the immediate observational period (maximum 46 weeks), until the first dose of the subsequent treatment cycle. |
| Part B: Percentage of Participants Who Achieved HAM-D Remission | Day 15 of Study Period 1, 2, 3, 4, and 5 | Remission was defined as having a HAM-D total score of ≤7. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. A Study Period is defined as Treatment Cycle (28 days) followed by the immediate observational period (maximum 46 weeks), until the first dose of the subsequent treatment cycle. Percentage are rounded off. |
| Parts A and B: Number of Participants Who Achieved the Requirements for Repeat Treatment for SAGE-217 | Up to 52 Weeks | Participants who continued in the study beyond 56 days from the last study drug dose (in parent study for Part B) and had a HAMD-17 total score ≥20 between the end of first treatment cycle and start of next treatment cycle qualified for repeat treatment for SAGE-217. The 17-item HAM-D was used for measuring severity of depression. It comprised individual ratings of following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. For Part B, data for this outcome measure is presented as per the designated arms in the parent study (217-MDD-305). |
| Parts A and B: Number of Repeat Treatment Cycles of SAGE-217 for Each Participant | Up to 52 Weeks | The response of initial treatment and/or repeat treatment was assessed by HAMD-17. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of following symptoms scored in range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Following symptoms were scored in range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. total score range=0 to 52, and higher scores indicated greater degree of depression. Participants who had a HAM-D total score \>=20 within the protocol were eligible for at least 1 repeat treatment in study. For Part B, data for this outcome measure is presented as per the designated arms in parent study (217-MDD-305). Participants who did not have any re-treatment were included with number of re-treatments equal to 0. |
| Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 in Study Period 1 | Baseline, Day 15 in Study Period 1 | The 17-item HAM-D scale was used for measuring severity of depression. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Each item is scored in a range of 0 to 2 or 0 to 4. The total score ranges from 0 to 52 with higher scores indicating a greater degree of depression. A negative change from baseline indicates improvement. A study period is a treatment cycle (treatment period+14-day follow-up) plus the observational period (until next treatment cycle or end of study, whichever is earlier) immediately following it. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 38 study sites in Part A and 52 study sites in Part B in the United States.
Pre-assignment details
Participants with Major Depressive Disorder (MDD) were enrolled in this study. This study was conducted in 2 parts, Part A enrolled de novo MDD participants and Part B enrolled MDD participants from the parent study 217- MDD-305 (NCT04476030). Data for Part B was collected and reported in a single arm for each participant who signed informed consent to enroll into this study to be treated with SAGE-217 if and when eligible to be treated.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Sage-217 High-dose Cohort Participants received SAGE-217, 50 milligrams (mg), orally, once daily from Day 1 through 14 followed by 14-day follow-up period. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. After the treatment period participants who had a response (a ≥50% reduction from baseline in Hamilton Rating Scale for Depression \[HAMD\]-17 total score by Day 15) entered a 48-week observational period. During the 48-week observational period, HAMD-17 responders returned to the site every 8 weeks for clinical assessments. Participants were assessed remotely every 14 days via the participant reported 9-item Patient Health Questionnaire (PHQ-9); participants with PHQ-9 score ≥10 returned to the site to be assessed by the clinician administered HAMD-17. If the HAMD-17 total score was ≥20 and 56 days had elapsed since the last dose of the investigational product (IP), the participant began a 14-day SAGE-217 treatment period, which was followed by a 14-day follow-up period. | 513 |
| Part A: Sage-217 Low-dose Cohort Participants received SAGE-217, 30 mg, orally, once daily from Day 1 through 14 followed by 14-day follow-up period. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. After the treatment period participants who had a response (a ≥50% reduction from baseline in HAMD-17 total score by Day 15) or remission entered a 48-week observational period. During the 48-week observational period, HAMD-17 responders returned to the site every 8 weeks for clinical assessments. Participants were assessed remotely every 14 days via the participant reported 9-item PHQ-9; participants with PHQ-9 score ≥10 returned to the site to be assessed by the clinician administered HAMD-17. If the HAMD-17 total score was ≥20 and 56 days had elapsed since the last dose of the IP, the participant began a 14-day SAGE-217 treatment period, which was followed by a 14-day follow-up period. | 645 |
| Part A: Sage-217 Dose-switch Cohort Participants received SAGE-217, 30 mg, orally, once daily in treatment Cycle 1 Day 1 through Day 14 followed by 14-day follow-up period and switched to 50 mg orally, once daily in a subsequent treatment cycle. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. After the treatment period participants who had a response (a ≥50% reduction from baseline in HAMD-17 total score by Day 15) or remission entered a 48-week observational period. During the 48-week observational period, HAMD-17 responders returned to the site every 8 weeks for clinical assessments. Participants were assessed remotely every 14 days via the participant reported 9-item PHQ-9; participants with PHQ-9 score ≥10 returned to the site to be assessed by the clinician administered HAMD-17. If the HAMD-17 total score was ≥20 and 56 days had elapsed since the last dose of the IP, the participant began a 14-day SAGE-217 treatment period, which was followed by a 14-day follow-up period. | 80 |
| Part B: Sage-217 Participants who were eligible to enter the current study from parent study 217-MDD-305 entered the 46-week observational period. Participants were followed with remote assessment of the participant-reported PHQ-9 every 2 weeks; if the PHQ-9 score was ≥10, the participant returned to the site approximately 1 week later and was assessed for the clinician administered HAMD-17. If the HAMD-17 total score was ≥20 and 56 days had elapsed since the last dose of IP, the participant began a 14-day SAGE-217 treatment period, which was followed by a 14-day follow-up period. Participants received SAGE-217 50 mg or 40 mg at the discretion of the investigator, orally, once daily for 14 days followed by 14-day follow-up period. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. | 190 |
| Total | 1,428 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 42 | 30 | 1 | 9 |
| Overall Study | Enrolled but did not receive SAGE-217 | 0 | 0 | 0 | 159 |
| Overall Study | Lost to Follow-up | 45 | 54 | 0 | 9 |
| Overall Study | Non-compliance With Investigational Drug | 4 | 4 | 0 | 0 |
| Overall Study | Other | 7 | 9 | 1 | 4 |
| Overall Study | Participant Did Not Meet 50% Reduction in HAMD-17 | 116 | 173 | 0 | 0 |
| Overall Study | Physician Decision | 7 | 10 | 1 | 5 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Deviation | 6 | 26 | 0 | 1 |
| Overall Study | Sponsor Decision | 1 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 72 | 100 | 1 | 21 |
Baseline characteristics
| Characteristic | Part B: Sage-217 | Part A: Sage-217 High-dose Cohort | Part A: Sage-217 Low-dose Cohort | Total | Part A: Sage-217 Dose-switch Cohort |
|---|---|---|---|---|---|
| Age, Continuous | 38.9 years STANDARD_DEVIATION 12.39 | 43.7 years STANDARD_DEVIATION 15.01 | 44.7 years STANDARD_DEVIATION 14.31 | 43.7 years STANDARD_DEVIATION 14.38 | 47.5 years STANDARD_DEVIATION 12.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 40 Participants | 111 Participants | 139 Participants | 327 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 150 Participants | 402 Participants | 506 Participants | 1101 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 6 Participants | 1 Participants | 7 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 18 Participants | 22 Participants | 46 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants | 45 Participants | 108 Participants | 191 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 7 Participants | 11 Participants | 18 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants | 8 Participants | 0 Participants |
| Race (NIH/OMB) White | 153 Participants | 432 Participants | 499 Participants | 1156 Participants | 72 Participants |
| Region of Enrollment United States | 190 participants | 513 participants | 645 participants | 1428 participants | 80 participants |
| Sex: Female, Male Female | 127 Participants | 331 Participants | 423 Participants | 947 Participants | 66 Participants |
| Sex: Female, Male Male | 63 Participants | 182 Participants | 222 Participants | 481 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 513 | 1 / 645 | 0 / 80 | 0 / 118 |
| other Total, other adverse events | 371 / 513 | 435 / 645 | 57 / 80 | 87 / 118 |
| serious Total, serious adverse events | 18 / 513 | 19 / 645 | 1 / 80 | 4 / 118 |
Outcome results
Primary
Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
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.
Time frame: Baseline up to 52 Weeks (Study Period 1-5)
Population: Safety Set included all participants who were administered SAGE-217. For Baseline: Number analyzed is participants of safety set who received SAGE-217 in corresponding study period; For Post-baseline: Number analyzed is participants with data available for analysis at a specific timepoint. A study period is a treatment cycle (treatment period+14-day follow-up) plus the observational period (until next treatment cycle or end of study, whichever is earlier) immediately following it.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SB: Baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SI: Baseline | 262 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SI: Post-baseline | 10 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SI: Baseline | 16 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SB: Post-baseline | 3 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SI: Baseline | 11 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SI: Post-baseline | 17 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SB: Baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SI: Post-baseline | 6 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SI: Baseline | 52 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SB: Baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SI: Baseline | 3 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SI: Post-baseline | 44 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SB: Baseline | 6 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SB: Post-baseline | 1 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SB: Baseline | 1 Participants |
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SI: Post-baseline | 128 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SI: Post-baseline | 3 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SI: Baseline | 264 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SI: Post-baseline | 141 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SB: Baseline | 8 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SB: Post-baseline | 1 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SI: Baseline | 57 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SI: Post-baseline | 51 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SB: Baseline | 0 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SI: Baseline | 23 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SI: Post-baseline | 22 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SB: Baseline | 0 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SI: Baseline | 8 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SI: Post-baseline | 9 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SB: Baseline | 0 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SI: Baseline | 1 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SB: Baseline | 0 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SI: Post-baseline | 14 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SI: Post-baseline | 9 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SB: Baseline | 0 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SB: Baseline | 0 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SI: Post-baseline | 10 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SB: Baseline | 0 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SI: Baseline | 16 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SI: Baseline | 29 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SI: Baseline | 1 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SB: Baseline | 0 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SI: Post-baseline | 11 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 1: SB: Baseline | 0 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 3: SI: Baseline | 12 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 5: SI: Post-baseline | 2 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 4: SI: Baseline | 10 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Suicidal Ideation (SI) or Suicidal Behavior (SB) as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | Study Period 2: SB: Post-baseline | 0 Participants |
Primary
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: Up to 52 Weeks
Population: Safety Set included all participants who were administered SAGE-217.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 374 Participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 437 Participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 57 Participants |
Primary
Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS
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.
Time frame: Baseline up to 46 Weeks (Study Period 1-5)
Population: Period-Specific Safety Set included all participants who signed ICF for 217-MDD-303B and were dosed in respective Study Period. A Study Period is a treatment cycle followed by the immediate observation period until the first dose of the subsequent treatment cycle. Data for Part B was collected and reported in a single arm for each participant who started treatment as specified.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 1: SI: Baseline | 17 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 1: SI: Post-baseline | 16 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 1: SB: Baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 1: SB: Post-baseline | 1 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 2: SI: Baseline | 19 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 2: SI: Post-baseline | 24 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 2: SB: Baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 2: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 3: SI: Baseline | 9 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 3: SI: Post-baseline | 9 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 3: SB: Baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 3: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 4: SI: Baseline | 5 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 4: SI: Post-baseline | 6 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 4: SB: Baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 4: SB: Post-baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 5: SI: Baseline | 1 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 5: SI: Post-baseline | 1 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 5: SB: Baseline | 0 Participants |
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With Suicidal Ideation (SI) and Suicidal Behavior (SB) as Assessed by the C-SSRS | Study Period 5: SB: Post-baseline | 0 Participants |
Primary
Part B: Number of Participants With TEAEs
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.
Time frame: Up to 46 Weeks
Population: Study-specific Safety Set included all participants who signed the ICF for 217-MDD-303B and had at least 1 dosing of SAGE-217 within 217-MDD-303B. Data for Part B was collected and reported in a single arm for each participant who started treatment as specified.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part B: Number of Participants With TEAEs | 87 Participants |
Secondary
Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 in Study Period 1
The 17-item HAM-D scale was used for measuring severity of depression. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Each item is scored in a range of 0 to 2 or 0 to 4. The total score ranges from 0 to 52 with higher scores indicating a greater degree of depression. A negative change from baseline indicates improvement. A study period is a treatment cycle (treatment period+14-day follow-up) plus the observational period (until next treatment cycle or end of study, whichever is earlier) immediately following it.
Time frame: Baseline, Day 15 in Study Period 1
Population: The Safety Set was defined as all participants who received SAGE-217. Overall number analyzed is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 in Study Period 1 | -15.3 score on a scale | Standard Deviation 6.58 |
| Part A: Sage-217 Low-dose Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 in Study Period 1 | -14.6 score on a scale | Standard Deviation 7.09 |
| Part A: Sage-217 Dose-switch Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 in Study Period 1 | -20.1 score on a scale | Standard Deviation 4.61 |
Secondary
Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle
The 17-item HAM-D scale was used for measuring severity of depression. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Each item is scored in a range of 0 to 2 or 0 to 4. The total score ranges from 0 to 52 with higher scores indicating a greater degree of depression. A negative change from baseline indicates improvement. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle.
Time frame: Baseline, Day 15 of treatment cycles 2, 3, 4, and 5
Population: FAS included all participants in the Safety Set who had HAMD-17 response at Treatment Cycle 1 Day 15 and a discontinuation from study date, if it existed, was after the end of Treatment Cycle 1. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at a specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 2: CFB at Day 15 | -13.3 score on a scale | Standard Deviation 6.36 |
| Part A: Sage-217 High-dose Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 3: CFB at Day 15 | -12.2 score on a scale | Standard Deviation 8.06 |
| Part A: Sage-217 High-dose Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 4: CFB at Day 15 | -11.1 score on a scale | Standard Deviation 6.42 |
| Part A: Sage-217 High-dose Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 5: CFB at Day 15 | -9.0 score on a scale | Standard Deviation 7.17 |
| Part A: Sage-217 Low-dose Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 5: CFB at Day 15 | -11.6 score on a scale | Standard Deviation 6.65 |
| Part A: Sage-217 Low-dose Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 2: CFB at Day 15 | -12.3 score on a scale | Standard Deviation 6.49 |
| Part A: Sage-217 Low-dose Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 4: CFB at Day 15 | -11.7 score on a scale | Standard Deviation 7.52 |
| Part A: Sage-217 Low-dose Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 3: CFB at Day 15 | -12.5 score on a scale | Standard Deviation 6.26 |
| Part A: Sage-217 Dose-switch Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 5: CFB at Day 15 | -17.5 score on a scale | Standard Deviation 8.47 |
| Part A: Sage-217 Dose-switch Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 3: CFB at Day 15 | -15.1 score on a scale | Standard Deviation 6.24 |
| Part A: Sage-217 Dose-switch Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 4: CFB at Day 15 | -15.8 score on a scale | Standard Deviation 7.12 |
| Part A: Sage-217 Dose-switch Cohort | Part A: Change From Baseline (CFB) in the HAMD-17 Total Score at Day 15 of Each Treatment Cycle | Treatment cycle 2: CFB at Day 15 | -15.4 score on a scale | Standard Deviation 7.21 |
Secondary
Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle
The CGI-S uses a 7-point Likert scale to rate the severity of the participant's mental illness at the time of assessment, relative to the clinician's past experience with participants who had the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=extremely ill. A higher score indicated extreme illness. A negative change from baseline indicated improvement. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle.
Time frame: Baseline, Day 15 of treatment cycles 2, 3, 4, and 5
Population: FAS included all participants in the Safety Set who had HAMD-17 response at Treatment Cycle 1 Day 15 and the discontinuation from study date, if it existed, was after the end of Treatment Cycle 1. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 2: CFB at Day 15 | -2.0 score on a scale | Standard Deviation 1.15 |
| Part A: Sage-217 High-dose Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 3: CFB at Day 15 | -1.8 score on a scale | Standard Deviation 1.32 |
| Part A: Sage-217 High-dose Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 4: CFB at Day 15 | -1.8 score on a scale | Standard Deviation 1.16 |
| Part A: Sage-217 High-dose Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 5: CFB at Day 15 | -1.2 score on a scale | Standard Deviation 1.27 |
| Part A: Sage-217 Low-dose Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 5: CFB at Day 15 | -1.9 score on a scale | Standard Deviation 1.09 |
| Part A: Sage-217 Low-dose Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 2: CFB at Day 15 | -1.9 score on a scale | Standard Deviation 1.23 |
| Part A: Sage-217 Low-dose Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 4: CFB at Day 15 | -1.7 score on a scale | Standard Deviation 1.33 |
| Part A: Sage-217 Low-dose Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 3: CFB at Day 15 | -1.8 score on a scale | Standard Deviation 1.21 |
| Part A: Sage-217 Dose-switch Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 5: CFB at Day 15 | -2.7 score on a scale | Standard Deviation 1.83 |
| Part A: Sage-217 Dose-switch Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 3: CFB at Day 15 | -2.1 score on a scale | Standard Deviation 1.35 |
| Part A: Sage-217 Dose-switch Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 4: CFB at Day 15 | -2.4 score on a scale | Standard Deviation 1.64 |
| Part A: Sage-217 Dose-switch Cohort | Part A: Change From Baseline in CGI-S Score During Each Treatment Cycle | Treatment Cycle 2: CFB at Day 15 | -2.2 score on a scale | Standard Deviation 1.43 |
Secondary
Part A: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score During Treatment Cycle 1
The CGI-S uses a 7-point Likert scale to rate the severity of the participant's mental illness at the time of assessment, relative to the clinician's past experience with participants who had the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=extremely ill. A higher score indicated extreme illness. A negative change from baseline indicated improvement. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle.
Time frame: Baseline, Day 15 of treatment cycle 1
Population: The Safety Set was defined as all participants who received SAGE-217. Overall number analyzed is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score During Treatment Cycle 1 | -2.3 score on a scale | Standard Deviation 1.22 |
| Part A: Sage-217 Low-dose Cohort | Part A: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score During Treatment Cycle 1 | -2.1 score on a scale | Standard Deviation 1.25 |
| Part A: Sage-217 Dose-switch Cohort | Part A: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score During Treatment Cycle 1 | -2.4 score on a scale | Standard Deviation 1.01 |
Secondary
Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period
The CGI scale consists of 3 items. Only the first 2 items are being used in this study. The CGI-I employed a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement compared to baseline, whether or not it was due entirely to drug treatment. Response choices included: 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The CGI-I is only rated at posttreatment assessments. CGI-I response was defined as having a CGI-I score of very much improved or much improved. A study period is a treatment cycle (treatment period+14-day follow-up) plus the observational period (until next treatment cycle or end of study, whichever is earlier) immediately following it. Percentage are rounded off.
Time frame: Day 15 of Study Periods 2, 3, 4, and 5
Population: FAS included all participants in the Safety Set who had HAMD-17 response at Treatment Cycle 1 Day 15 and the discontinuation from study date, if it existed, was after the end of Treatment Cycle 1. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specific timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 2: Day 15 | 76.7 percentage of participants |
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 3: Day 15 | 65.2 percentage of participants |
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 4: Day 15 | 52.9 percentage of participants |
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 5: Day 15 | 33.3 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 5: Day 15 | 68.8 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 2: Day 15 | 75.0 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 4: Day 15 | 60.0 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 3: Day 15 | 73.2 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 5: Day 15 | 90.9 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 3: Day 15 | 80.9 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 4: Day 15 | 84.9 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved CGI-I Response During Each Study Period | Study Period 2: Day 15 | 79.5 percentage of participants |
Secondary
Part A: Percentage of Participants Who Achieved Clinical Global Impression - Improvement (CGI-I) Response During Treatment Cycle 1
The CGI scale consists of 3 items. Only the first 2 items are being used in this study. The CGI-I employed a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement compared to baseline, whether or not it was due entirely to drug treatment. Response choices included: 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The CGI-I is only rated at posttreatment assessments. CGI-I response was defined as having a CGI-I score of very much improved or much improved. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. Percentage are rounded off.
Time frame: Day 15 of treatment cycle 1
Population: The Safety Set was defined as all participants who received SAGE-217. Overall number analyzed is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved Clinical Global Impression - Improvement (CGI-I) Response During Treatment Cycle 1 | 78.9 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved Clinical Global Impression - Improvement (CGI-I) Response During Treatment Cycle 1 | 75.0 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved Clinical Global Impression - Improvement (CGI-I) Response During Treatment Cycle 1 | 96.3 percentage of participants |
Secondary
Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period
Remission was defined as having a HAM-D total score of ≤7. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. A study period is a treatment cycle (treatment period+14-day follow-up) plus the observational period (until next treatment cycle or end of study, whichever is earlier) immediately following it. Percentage are rounded off.
Time frame: Day 15 of Study Periods 2, 3, 4, and 5
Population: FAS included all participants in the Safety Set who had HAMD-17 response at Treatment Cycle 1 Day 15 and the discontinuation from study date, if it existed, was after the end of Treatment Cycle 1. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available at a given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 2: Day 15 | 38.7 percentage of participants |
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 3: Day 15 | 34.8 percentage of participants |
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 4: Day 15 | 23.5 percentage of participants |
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 5: Day 15 | 16.7 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 5: Day 15 | 29.4 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 2: Day 15 | 31.9 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 4: Day 15 | 32.5 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 3: Day 15 | 29.6 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 5: Day 15 | 63.6 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 3: Day 15 | 32.9 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 4: Day 15 | 43.4 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Each Study Period | Study Period 2: Day 15 | 37.2 percentage of participants |
Secondary
Part A: Percentage of Participants Who Achieved HAM-D Remission During Treatment Cycle 1
Remission was defined as having a HAM-D total score of ≤7. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. Percentage are rounded off.
Time frame: Day 15 of treatment cycle 1
Population: The Safety Set was defined as all participants who received SAGE-217. Overall number analyzed is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Treatment Cycle 1 | 40.9 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Treatment Cycle 1 | 40.2 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved HAM-D Remission During Treatment Cycle 1 | 40.0 percentage of participants |
Secondary
Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period
HAM-D response was defined as a ≥50% reduction in HAM-D score from baseline, at the end of each 14-day treatment period. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. A study period is a treatment cycle (treatment period+14-day follow-up) plus the observational period (until next treatment cycle or end of study, whichever is earlier) immediately following it. Percentage are rounded off.
Time frame: Day 15 of Study Period 2, 3, 4, and 5
Population: FAS included all participants in the Safety Set who had HAMD-17 response at Treatment Cycle 1 Day 15 and the discontinuation from study date, if it existed, was after the end of Treatment Cycle 1. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 2: Day 15 | 65.3 percentage of participants |
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 3: Day 15 | 58.0 percentage of participants |
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 4: Day 15 | 38.2 percentage of participants |
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 5: Day 15 | 25.0 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 5: Day 15 | 58.8 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 2: Day 15 | 62.8 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 4: Day 15 | 55.0 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 3: Day 15 | 59.3 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 5: Day 15 | 81.8 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 3: Day 15 | 68.6 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 4: Day 15 | 75.5 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Each Study Period | Study Period 2: Day 15 | 67.9 percentage of participants |
Secondary
Part A: Percentage of Participants Who Achieved HAM-D Response During Treatment Cycle 1
HAM-D response was defined as a ≥50% reduction in HAM-D score from baseline, at the end of each 14-day treatment period. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. Each 14-day treatment period plus corresponding 14-day follow-up period was considered a treatment cycle. Percentage are rounded off.
Time frame: Day 15 of treatment cycle 1
Population: The Safety Set was defined as all participants who received SAGE-217. Overall number analyzed is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Treatment Cycle 1 | 67.3 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Treatment Cycle 1 | 65.9 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part A: Percentage of Participants Who Achieved HAM-D Response During Treatment Cycle 1 | 100 percentage of participants |
Secondary
Part B: Change From Baseline in CGI-S Score
The CGI-S uses a 7-point Likert scale to rate the severity of the participant's mental illness at the time of assessment, relative to the clinician's past experience with participants who had the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=extremely ill. A higher score indicated extreme illness. A negative change from baseline indicated improvement. A Study Period is defined as Treatment Cycle (28 days) followed by the immediate observational period (maximum 46 weeks), until the first dose of the subsequent treatment cycle.
Time frame: Baseline Day 15 of Study Period 1, 2, 3, 4, and 5
Population: FAS included all participants who signed the ICF for 217-MDD-303B and had at least 1 dosing of SAGE-217 within 217-MDD-303B and had at least 1 HAMD-17 total score available after the first dose of SAGE-217 within 217-MDD-303B. Overall number of participants analyzed is participants in FAS who were dosed in the specific period. Data for this outcome measure was collected and analyzed as per study period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part B: Change From Baseline in CGI-S Score | -1.5 score on a scale | Standard Deviation 1.18 |
| Part A: Sage-217 Low-dose Cohort | Part B: Change From Baseline in CGI-S Score | -1.8 score on a scale | Standard Deviation 1.15 |
| Part A: Sage-217 Dose-switch Cohort | Part B: Change From Baseline in CGI-S Score | -1.7 score on a scale | Standard Deviation 1.26 |
| Part B: SAGE-217 + ADT | Part B: Change From Baseline in CGI-S Score | -1.4 score on a scale | Standard Deviation 1.39 |
| Part B: SAGE-217 + ADT | Part B: Change From Baseline in CGI-S Score | -1.4 score on a scale | Standard Deviation 1.52 |
Secondary
Part B: Change From Baseline in the HAMD-17 Total Score at Day 15 of Each Treatment (Initial and/or Repeat Treatment) Cycle
The 17-item HAM-D scale was used to measure the severity of depression. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Each item is scored in a range of 0 to 2 or 0 to 4. The total score ranges from 0 to 52 with higher scores indicating a greater degree of depression. A negative change from baseline indicates improvement. Study period is defined as treatment cycle (28 days) followed by immediate observation period (maximum 46 weeks), until the first dose of the subsequent treatment cycle.
Time frame: Baseline, Day 15 of Study Period 1, 2, 3, 4, and 5
Population: FAS included all participants who signed the ICF for 217-MDD-303B and had at least 1 dosing of SAGE-217 within 217-MDD-303B and had at least 1 HAMD-17 total score available after the first dose of SAGE-217 within 217-MDD-303B. Overall number of participants analyzed is participants in FAS who were dosed in the specific period. Data for this outcome measure was collected and analyzed as per study period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part B: Change From Baseline in the HAMD-17 Total Score at Day 15 of Each Treatment (Initial and/or Repeat Treatment) Cycle | -10.1 score on a scale | Standard Deviation 6.43 |
| Part A: Sage-217 Low-dose Cohort | Part B: Change From Baseline in the HAMD-17 Total Score at Day 15 of Each Treatment (Initial and/or Repeat Treatment) Cycle | -10.7 score on a scale | Standard Deviation 6.49 |
| Part A: Sage-217 Dose-switch Cohort | Part B: Change From Baseline in the HAMD-17 Total Score at Day 15 of Each Treatment (Initial and/or Repeat Treatment) Cycle | -9.6 score on a scale | Standard Deviation 7.53 |
| Part B: SAGE-217 + ADT | Part B: Change From Baseline in the HAMD-17 Total Score at Day 15 of Each Treatment (Initial and/or Repeat Treatment) Cycle | -9.7 score on a scale | Standard Deviation 7.6 |
| Part B: SAGE-217 + ADT | Part B: Change From Baseline in the HAMD-17 Total Score at Day 15 of Each Treatment (Initial and/or Repeat Treatment) Cycle | -10.8 score on a scale | Standard Deviation 9.26 |
Secondary
Part B: Percentage of Participants Who Achieved CGI-I Response
The CGI scale consists of 3 items. Only the first 2 items are being used in this study. The CGI-I employed a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement compared to baseline, whether or not it was due entirely to drug treatment. Response choices included: 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The CGI-I is only rated at posttreatment assessments. CGI-I response was defined as having a CGI-I score of very much improved or much improved. A Study Period is defined as Treatment Cycle (28 days) followed by the immediate observational period (maximum 46 weeks), until the first dose of the subsequent treatment cycle. Percentage are rounded off.
Time frame: Day 15 of Study Period 1, 2, 3, 4, and 5
Population: FAS included all participants who signed the ICF for 217-MDD-303B and had at least 1 dosing of SAGE-217 within 217-MDD-303B and had at least 1 HAMD-17 total score available after the first dose of SAGE-217 within 217-MDD-303B. Overall number of participants analyzed is participants in FAS who were dosed in the specific period. Data for this outcome measure was collected and analyzed as per study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part B: Percentage of Participants Who Achieved CGI-I Response | 53.8 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part B: Percentage of Participants Who Achieved CGI-I Response | 63.5 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part B: Percentage of Participants Who Achieved CGI-I Response | 64.3 percentage of participants |
| Part B: SAGE-217 + ADT | Part B: Percentage of Participants Who Achieved CGI-I Response | 55.0 percentage of participants |
| Part B: SAGE-217 + ADT | Part B: Percentage of Participants Who Achieved CGI-I Response | 60.0 percentage of participants |
Secondary
Part B: Percentage of Participants Who Achieved HAM-D Remission
Remission was defined as having a HAM-D total score of ≤7. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. A Study Period is defined as Treatment Cycle (28 days) followed by the immediate observational period (maximum 46 weeks), until the first dose of the subsequent treatment cycle. Percentage are rounded off.
Time frame: Day 15 of Study Period 1, 2, 3, 4, and 5
Population: FAS included all participants who signed the ICF for 217-MDD-303B and had at least 1 dosing of SAGE-217 within 217-MDD-303B and had at least 1 HAMD-17 total score available after the first dose of SAGE-217 within 217-MDD-303B. Overall number of participants analyzed is participants in FAS who were dosed in the specific period. Data for this outcome measure was collected and analyzed as per study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part B: Percentage of Participants Who Achieved HAM-D Remission | 19.2 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part B: Percentage of Participants Who Achieved HAM-D Remission | 29.4 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part B: Percentage of Participants Who Achieved HAM-D Remission | 26.2 percentage of participants |
| Part B: SAGE-217 + ADT | Part B: Percentage of Participants Who Achieved HAM-D Remission | 20.0 percentage of participants |
| Part B: SAGE-217 + ADT | Part B: Percentage of Participants Who Achieved HAM-D Remission | 40.0 percentage of participants |
Secondary
Part B: Percentage of Participants Who Achieved HAM-D Response
HAM-D response was defined as a ≥50% reduction in HAM-D score from baseline, at the end of each 14-day treatment period. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. A study period is defined as treatment cycle (28 days) followed by immediate observation period (maximum 46 weeks), until the first dose of the subsequent treatment cycle. Percentage are rounded off.
Time frame: Day 15 of Study Period 1, 2, 3, 4, and 5
Population: FAS included all participants who signed the ICF for 217-MDD-303B and had at least 1 dosing of SAGE-217 within 217-MDD-303B and had at least 1 HAMD-17 total score available after the first dose of SAGE-217 within 217-MDD-303B. Overall number of participants analyzed is participants in FAS who were dosed in the specific period. Data for this outcome measure was collected and analyzed as per study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Sage-217 High-dose Cohort | Part B: Percentage of Participants Who Achieved HAM-D Response | 46.2 percentage of participants |
| Part A: Sage-217 Low-dose Cohort | Part B: Percentage of Participants Who Achieved HAM-D Response | 47.1 percentage of participants |
| Part A: Sage-217 Dose-switch Cohort | Part B: Percentage of Participants Who Achieved HAM-D Response | 38.1 percentage of participants |
| Part B: SAGE-217 + ADT | Part B: Percentage of Participants Who Achieved HAM-D Response | 30.0 percentage of participants |
| Part B: SAGE-217 + ADT | Part B: Percentage of Participants Who Achieved HAM-D Response | 60.0 percentage of participants |
Secondary
Parts A and B: Number of Participants Who Achieved the Requirements for Repeat Treatment for SAGE-217
Participants who continued in the study beyond 56 days from the last study drug dose (in parent study for Part B) and had a HAMD-17 total score ≥20 between the end of first treatment cycle and start of next treatment cycle qualified for repeat treatment for SAGE-217. The 17-item HAM-D was used for measuring severity of depression. It comprised individual ratings of following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following symptoms 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 can range from 0 to 52, and higher scores indicated a greater degree of depression. For Part B, data for this outcome measure is presented as per the designated arms in the parent study (217-MDD-305).
Time frame: Up to 52 Weeks
Population: For Part A: FAS included all participants in the Safety Set who had HAMD-17 response at Treatment Cycle 1 Day 15 and the discontinuation from study date, if it existed, was after the end of Treatment Cycle 1. For Part B: FAS included all participants in the study-specific safety set (dosed at least once within this protocol) who had at least 1 HAMD-17 total score available after the first dose of SAGE-217 within 217-MDD-303B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Sage-217 High-dose Cohort | Parts A and B: Number of Participants Who Achieved the Requirements for Repeat Treatment for SAGE-217 | 174 Participants |
| Part A: Sage-217 Low-dose Cohort | Parts A and B: Number of Participants Who Achieved the Requirements for Repeat Treatment for SAGE-217 | 224 Participants |
| Part A: Sage-217 Dose-switch Cohort | Parts A and B: Number of Participants Who Achieved the Requirements for Repeat Treatment for SAGE-217 | 80 Participants |
| Part B: SAGE-217 + ADT | Parts A and B: Number of Participants Who Achieved the Requirements for Repeat Treatment for SAGE-217 | 28 Participants |
| Part B: SAGE-217 + ADT | Parts A and B: Number of Participants Who Achieved the Requirements for Repeat Treatment for SAGE-217 | 61 Participants |
Secondary
Parts A and B: Number of Repeat Treatment Cycles of SAGE-217 for Each Participant
The response of initial treatment and/or repeat treatment was assessed by HAMD-17. The 17-item HAM-D scale was used for measuring severity of depression. The HAM-D comprised individual ratings of following symptoms scored in range of 0 to 2: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Following symptoms were scored in range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. total score range=0 to 52, and higher scores indicated greater degree of depression. Participants who had a HAM-D total score \>=20 within the protocol were eligible for at least 1 repeat treatment in study. For Part B, data for this outcome measure is presented as per the designated arms in parent study (217-MDD-305). Participants who did not have any re-treatment were included with number of re-treatments equal to 0.
Time frame: Up to 52 Weeks
Population: For Part A: FAS included all participants in safety set who had HAMD-17 response at Treatment Cycle 1 Day 15 and discontinuation from study date, if it existed, was after end of Treatment Cycle 1. For Part B: FAS included all participants in study-specific safety set (dosed at least once within this protocol) who had at least 1 HAMD-17 total score available after first dose of SAGE-217 within 217-MDD-303B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Sage-217 High-dose Cohort | Parts A and B: Number of Repeat Treatment Cycles of SAGE-217 for Each Participant | 0.8 repeat treatment cycles | Standard Deviation 1.11 |
| Part A: Sage-217 Low-dose Cohort | Parts A and B: Number of Repeat Treatment Cycles of SAGE-217 for Each Participant | 0.9 repeat treatment cycles | Standard Deviation 1.13 |
| Part A: Sage-217 Dose-switch Cohort | Parts A and B: Number of Repeat Treatment Cycles of SAGE-217 for Each Participant | 2.8 repeat treatment cycles | Standard Deviation 0.97 |
| Part B: SAGE-217 + ADT | Parts A and B: Number of Repeat Treatment Cycles of SAGE-217 for Each Participant | 1.6 repeat treatment cycles | Standard Deviation 0.8 |
| Part B: SAGE-217 + ADT | Parts A and B: Number of Repeat Treatment Cycles of SAGE-217 for Each Participant | 1.9 repeat treatment cycles | Standard Deviation 0.97 |
Secondary
Parts A and B: Time to First Repeat Treatment With SAGE-217
For Part A, the first day of the first repeat treatment is Treatment Cycle 2 Day 1. For Part B, participants who had placebo + ADT in the parent study (217-MDD-305), the first repeat treatment of SAGE-217 was the second treatment within MDD-303B. Participants who had SAGE-217 + ADT in the parent study (217-MDD-305), the first repeat treatment of SAGE-217 was the first treatment within MDD-303B. For Part A, as prespecified, data for this outcome measure was collected for Sage-217 High-dose Cohort and Sage-217 30 mg Cohort (Low Dose + Dose Switch). For Part B, data for this outcome measure is presented as per the designated arms in the parent study (217-MDD-305). Analysis used Kaplan-Meier estimates where the participants with no repeat treatment were censored.
Time frame: Up to 52 Weeks
Population: For Part A: FAS included all participants in the Safety Set who had HAMD-17 (change from baseline \>=50%) response at Treatment Cycle 1 Day 15 and the discontinuation from study date, if it existed, was after the end of Treatment Cycle 1. For Part B: Safety Set included all participants who received a dose of SAGE-217 either in the parent study 217-MDD-305 or within this protocol 217-MDD-303B.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Sage-217 High-dose Cohort | Parts A and B: Time to First Repeat Treatment With SAGE-217 | 281 days |
| Part A: Sage-217 Low-dose Cohort | Parts A and B: Time to First Repeat Treatment With SAGE-217 | 135 days |
| Part A: Sage-217 Dose-switch Cohort | Parts A and B: Time to First Repeat Treatment With SAGE-217 | 79 days |
| Part B: SAGE-217 + ADT | Parts A and B: Time to First Repeat Treatment With SAGE-217 | 233 days |