Back to resultsA Study to Evaluate SAGE-547 in Participants With Severe Postpartum Depression
Primary Purpose
Severe Postpartum Depression
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
SAGE-547
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Severe Postpartum Depression
Eligibility Criteria
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.
Sites / Locations
- Sage Investigational Site
- Sage Investigational Site
- Sage Investigational Site
- Sage Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
SAGE-547
Arm Description
Participants received infusion rates of placebo matched to SAGE-547.
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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".
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02614547
Brief Title
A Study to Evaluate SAGE-547 in Participants With Severe Postpartum Depression
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
December 15, 2015 (Actual)
Primary Completion Date
June 22, 2016 (Actual)
Study Completion Date
June 22, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sage Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Postpartum Depression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received infusion rates of placebo matched to SAGE-547.
Arm Title
SAGE-547
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
SAGE-547
Intervention Description
Administered as intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered as intravenous infusion.
Primary Outcome Measure Information:
Title
Change From Baseline at End of Treatment Period (at 60 Hours) in Hamilton Rating Scale for Depression (HAM-D) Total Score
Description
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.
Time Frame
Baseline, 60 Hours
Secondary Outcome Measure Information:
Title
Percentage of Participants With HAM-D Response
Description
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.
Time Frame
60 Hours, Days 7 and 30
Title
Percentage of Participants With HAM-D Remission
Description
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.
Time Frame
60 Hours, Days 7, and 30
Title
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description
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.
Time Frame
Baseline, 60 Hours, Days 7 and 30
Title
Percentage of Participants With Clinical Global Impression-Improvement (CGI-I) Response
Description
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".
Time Frame
60 Hours, Days 7 and 30
Title
Change From Baseline in HAM-D Bech 6 Subscale
Description
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.
Time Frame
Baseline, 60 Hours, Days 7 and 30
Title
Change From Baseline to 60 Hours in the HAM-D Individual Item Scores
Description
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.
Time Frame
Baseline, 60 Hours
Title
Change From Baseline in Generalized Anxiety Disorder 7-item Scale (GAD-7) Total Score
Description
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.
Time Frame
Baseline, 60 Hours, Day 7 and 30
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Up to 30 days
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen J Kanes, MD, PhD
Organizational Affiliation
Sage Therapeutics
Official's Role
Study Chair
Facility Information:
Facility Name
Sage Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Sage Investigational Site
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Sage Investigational Site
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Sage Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
Citations:
PubMed Identifier
33181049
Citation
Gerbasi ME, Meltzer-Brody S, Acaster S, Fridman M, Bonthapally V, Hodgkins P, Kanes SJ, Eldar-Lissai A. Brexanolone in Postpartum Depression: Post Hoc Analyses to Help Inform Clinical Decision-Making. J Womens Health (Larchmt). 2021 Mar;30(3):385-392. doi: 10.1089/jwh.2020.8483. Epub 2020 Nov 12.
Results Reference
derived
PubMed Identifier
28619476
Citation
Kanes S, Colquhoun H, Gunduz-Bruce H, Raines S, Arnold R, Schacterle A, Doherty J, Epperson CN, Deligiannidis KM, Riesenberg R, Hoffmann E, Rubinow D, Jonas J, Paul S, Meltzer-Brody S. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet. 2017 Jul 29;390(10093):480-489. doi: 10.1016/S0140-6736(17)31264-3. Epub 2017 Jun 12.
Results Reference
derived
Links:
URL
http://www.sagerx.com
Description
Related Info
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A Study to Evaluate SAGE-547 in Participants With Severe Postpartum Depression
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