A Study to Evaluate SAGE-217 in Participants With Severe Postpartum Depression

The 17-item HAM-D is used to rate the severity of depression in participants who are already diagnosed as depressed. Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items are scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. Higher scores indicated more severe depression. A negative change from Baseline indicates less depression.

HAM-D Response was defined as having a 50 percent (%) or greater reduction from Baseline in HAM-D total score. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. The items on HAM-D included: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early night, middle night, early hours [morning]), 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. Higher scores indicated more depression.

HAM-D Remission was defined as a HAM-D total score of less than or equal to (<=)7. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. The items on HAM-D included: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early night, middle night, early hours [morning]), 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. Higher scores indicated more depression.

HAM-D is used to rate the severity of depression in participants who are already diagnosed as depressed. HAM-D subscales: Core subscale (symptoms-depressed mood, feelings of guilt, suicide, work and activities, and retardation ); Anxiety subscale (symptoms-anxiety [psychic and somatic], somatic symptoms [gastrointestinal and general], hypochondriasis, loss of weight); Bech-6 subscale (symptoms-depressed mood, feelings of guilt, work and activities, retardation, anxiety psychic, and somatic symptoms general); Meier subscale (symptoms-depressed mood, feelings of guilt, work and activities, retardation, agitation, and anxiety psychic). Each item was scored in a range of 0 to 2 or 0 to 4, higher scores=greater degree of depression. Subscale scores were calculated as the sum of the individual item scores comprising each subscale. Scores were transformed to a scale of 0 to 100, with higher scores indicated more severe depression. A negative change from Baseline indicates less depression.

The 17-item HAM-D is used to rate the severity of depression in participants who are already diagnosed as depressed. Individual items on the scale were scored in a range of 0 to 2 or 0 to 4. 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. Higher scores indicated a greater degree of depression. A negative change from Baseline indicates less depression.

The MADRS is a 10-item questionnaire used to measure the severity of depressive episodes in participants with mood disorders. It includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; and suicidal thoughts. Each item was scored in a range of 0 (no symptoms) to 6 (symptoms of maximum severity). The MADRS total score was calculated as the sum of the 10 individual item scores and could range from 0 to 60. Higher scores indicated more severe depression. A negative change from Baseline indicates less depression.

The Clinical Global Impression - Improvement (CGI-I) item of the CGI scale uses a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The investigator rated the participant's total improvement 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. CGI response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved). The percentage of participants with overall improvement in post-treatment condition, rated by investigator as very much improved (CGI-I score of 1) or much improved (CGI-I score of 2) is reported.

The 14-item HAM-A was used to rate the severity of symptoms of anxiety. Each of the 14 items was defined by a series of symptoms and measured both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The individual items were scored in a range of 0 (not present) to 4 (very severe). The HAM-A total score was calculated as the sum of the 14 individual item scores and could range from 0 to 56 where a score of <17=mild severity; 18-24= mild to moderate severity and 25-30=moderate to severe severity. A negative change from Baseline indicates less anxiety.

MADRS response was defined as having a 50% or greater reduction from Baseline in MADRS total score. The MADRS is a 10-item questionnaire used to measure the severity of depressive episodes in participants with mood disorders. It includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; and suicidal thoughts. Each item was scored in a range of 0 (no symptoms) to 6 (symptoms of maximum severity). The MADRS total score was calculated as the sum of the 10 individual item scores and could range from 0 to 60. Higher scores indicated more depression.

MADRS Remission was defined as a MADRS total score of <=10. The MADRS is a 10-item questionnaire used to measure the severity of depressive episodes in participants with mood disorders. It includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; and suicidal thoughts. Each item was scored in a range of 0 (no symptoms) to 6 (symptoms of maximum severity). The MADRS total score was calculated as the sum of the 10 individual item scores and could range from 0 to 60. Higher scores indicated more depression.

An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE with an onset that occurs after receiving study drug.

Vital signs included assessments of supine and standing systolic blood pressure (SBP), supine and standing diastolic blood pressure (DBP), and heart rate.

Laboratory tests included tests of Hematology, Chemistry, and Urinalysis.

ECG parameters included assessment of the standard 12-lead ECG intervals: QT, QTcF, PR, RR, QRS, and heart rate. Heart rate was measured in terms of beats per minute. Change from Baseline in heart rate at specified time points were reported.

ECG parameters included assessment of the standard 12-lead ECG intervals: QT, QTcF, PR, RR, QRS, and heart rate. Change from Baseline in PR Interval, RR Interval, QRS Duration, QT Interval, QTcF Interval is reported.

C-SSRS was used to assess the suicidality of participants during the study. The assessment included "yes" or "no" responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings were provided for severity of ideation (if present), from 1 to 5, with 5 being the most severe. Number of participants with a response of 'yes' to any suicidal ideation or suicidal behavior item as measured by C-SSRS is reported.