A Study to Evaluate SAGE-547 in Participants With Severe Postpartum Depression

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled study of the efficacy, safety, and pharmacokinetics of SAGE-547 Injection in adult female participants diagnosed with severe postpartum depression.

Official Title
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A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Evaluating The Efficacy, Safety, And Pharmacokinetics Of SAGE-547 Injection In The Treatment Of Adult Female Subjects With Severe Postpartum Depression

Conditions
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Severe Postpartum Depression

Intervention / Treatment
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* Drug: SAGE-547
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participant either must have ceased lactating at Screening; or if still lactating at Screening, must have already fully and permanently weaned their infant(s) from breastmilk; or if still actively breastfeeding at Screening, must agree to cease giving breastmilk to their infant(s) prior to receiving study drug. Participant had a major depressive episode that began no earlier than the third trimester and no later than the first 4 weeks following delivery, as diagnosed by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Participant was less than or equal to (<=) six months postpartum. Participant must be amenable to intravenous therapy. Key Exclusion Criteria: Active psychosis. Attempted suicide associated with index case of postpartum depression. Medical history of seizures. Medical history of bipolar disorder. Note: suicidal ideation was not an exclusion. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received infusion rates of placebo matched to SAGE-547. | Drug: Placebo<br>* Administered as intravenous infusion.<br>|
| Experimental: SAGE-547<br>Participants received a 4-hour dose titration of 30 micrograms per kilogram per hour (micrograms/kg/hr) (0 to 4 hours), then 60 micrograms/kg/hr (4 to 24 hours), then 90 micrograms/kg/hr (24 to 52 hours), followed by a taper to 60 micrograms/kg/hr (52 to 56 hours), and 30 micrograms/kg/hr (56 to 60 hours). | Drug: SAGE-547<br>* Administered as intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at End of Treatment Period (at 60 Hours) in Hamilton Rating Scale for Depression (HAM-D) Total Score | The HAM-D total score comprises a sum of the 17 individual item scores. 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 total score can range from 0 to 52, and higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression. | Baseline, 60 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HAM-D Response | The 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 comprises a sum of the 17 individual item scores. 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 total score can range from 0 to 52, and higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression. | 60 Hours, Days 7 and 30 | 
| Percentage of Participants With HAM-D Remission | The HAM-D remission was defined as having a HAM-D total score of less than or equal to (<=)7. The HAM-D total score comprises a sum of the 17 individual item scores. 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 total score can range from 0 to 52, and higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression. | 60 Hours, Days 7, and 30 | 
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | The MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in participants with mood disorders. It was designed as an adjunct to the HAM-D, to be more sensitive than the Hamilton Scale to the changes brought on by antidepressants and other forms of treatment. Each item yielded a score of 0 to 6. The MADRS total score was calculated as the sum of the 10 individual item scores, which ranged from 0 to 60. Higher MADRS scores indicate more severe depression. A negative change from baseline indicate less severe depression. A positive change from baseline indicates more severe depression. | Baseline, 60 Hours, Days 7 and 30 | 
| Percentage of Participants With Clinical Global Impression-Improvement (CGI-I) Response | The CGI-I item employs a 7-point Likert scale to measure the overall improvement in the participant's condition post-treatment. The investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. Response choices include: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The CGI-I was only rated at post-treatment assessments, and by definition, was evaluated against baseline conditions. CGI-I response was defined as having a CGI-I score of very much improved or much improved. | 60 Hours, Days 7 and 30 | 
| Change From Baseline in HAM-D Bech 6 Subscale | The HAM-D Bech 6 subscale score was calculated as the sum of the following six items: depressed mood, feelings of guilt, work and activities, retardation, psychic anxiety, and general somatic symptoms. Each item is scored in a range of 0 to 2 or 0 to 4, with higher scores indicating a greater degree of depression. The scores were transformed to a scale of 0 to 100, with a higher score indicating a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression. | Baseline, 60 Hours, Days 7 and 30 | 
| Change From Baseline to 60 Hours in the HAM-D Individual Item Scores | The HAM-D comprises 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 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. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression. | Baseline, 60 Hours | 
| Change From Baseline in Generalized Anxiety Disorder 7-item Scale (GAD-7) Total Score | The GAD-7 is a participant-rated, generalized anxiety symptom severity scale. Scoring for GAD-7 generalized anxiety is calculated by assigning scores of 0 = not at all sure, 1 = several days, 2 = over half the days, and 3 = nearly every day to the response categories. The GAD-7 total score for the seven items ranges from 0 to 21, where a score of 0 to 4 = minimal anxiety, 5 to 9 = mild anxiety, 10 to 14 = moderate anxiety, and 15 to 21 = severe anxiety. The GAD-7 total score was calculated as the sum of the seven individual item scores. A negative change from baseline indicates less anxiety. A positive change from baseline indicates more anxiety. | Baseline, 60 Hours, Day 7 and 30 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, 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 onset on or after the start of study drug infusion, or any worsening of a pre-existing medical condition/AE with onset on or after the start of study drug infusion. | Up to 30 days |