A Study to Evaluate SAGE-217 in Adult Participants With Major Depressive Disorder (MDD)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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