A Study to Evaluate Safety and Efficacy of SAGE-547 in Participants With Moderate Postpartum Depression (547-PPD-202C)

• ClinicalTrials.gov Identifier: NCT02942017
• Recruitment Status: Completed
• First Posted: October 21, 2016
• Results First Posted: June 13, 2019
• Last Update Posted: January 28, 2022
• Sponsor: Sage Therapeutics
• Information provided by (Responsible Party): Sage Therapeutics

Study Description

Brief Summary:

The purpose of this study was to determine if SAGE-547 Injection infused intravenously at up to 90 μg/kg/h for 60 hours reduces depressive symptoms in participants with moderate postpartum depression (PPD) compared to placebo injection as assessed by the change from baseline in Hamilton Rating Scale for Depression (HAM-D) total score.

Condition or disease	Intervention/treatment	Phase
Postpartum Depression	Drug: Placebo; Drug: SAGE-547 90 μg/kg/h	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 108 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 and Adult Female Subjects With Moderate Postpartum Depression
• Study Start Date: July 2016
• Actual Primary Completion Date: September 17, 2017
• Actual Study Completion Date: October 11, 2017

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Participants received an infusion rate equivalent to the 90 micrograms per kilogram per hour (μg/kg/h) group.	Drug: Placebo; Intravenous infusion of matching placebo for SAGE-547.
Experimental: SAGE-547 90 μg/kg/h; Participants received a 4-hour dose titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 24 hours), then 90 μg/kg/h (24 to 52 hours), followed by a taper to 60 μg/kg/h (52 to 56 hours), and 30 μg/kg/h (56 to 60 hours).	Drug: SAGE-547 90 μg/kg/h; Intravenous infusion of SAGE-547

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline at 60 Hours in 17-Item Hamilton Rating Scale for Depression (HAM-D) Total Score [ Time Frame: Baseline, Hour 60 ]
   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. 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 :

1. Change From Baseline in HAM-D Total Score at Day 30 [ Time Frame: Baseline, Day 30 ]
   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. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.
2. Change From Baseline in HAM-D Total Score [ Time Frame: Baseline, Hours 2, 4, 8, 12, 24, 36, 48, 72, and Days 7, 14 and 21 ]
   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. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.
3. Percentage of Participants With HAM-D Response [ Time Frame: Hour 60, Days 7 and 30 ]
   The HAM-D response is defined as having a 50% 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. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.
4. Percentage of Participants With HAM-D Remission [ Time Frame: Hour 60, Days 7 and 30 ]
   HAM-D remission is defined as having a HAM-D total score of ≤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. Higher scores indicate a greater degree of depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.
5. Change From Baseline in HAM-D Bech 6 Subscale [ Time Frame: Baseline, Hour 60, Days 7 and 30 ]
   The HAM-D Bech 6 subscale score is calculated as the sum of the following six items: Item # 1 (depressed mood), Item # 2 (feelings of guilt), Item # 7 (work and activities), Item # 8 (retardation), Item # 10 (anxiety psychic), and Item # 13 (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 100-point scale 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.
6. Change From Baseline in HAM-D Individual Item Scores [ Time Frame: Baseline, Hours 2, 4, 8, 12, 24, 36, 48, 60, 72, and Days 7, 14, 21, and 30 ]
   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.
7. Change From Baseline at Key Time Points in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline, Hour 60, Days 7 and 30 ]
   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 indicates more severe depression. A negative change from baseline indicates less severe depression. A positive change from baseline indicates more severe depression.
8. Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response [ Time Frame: Hour 60, Days 7 and 30 ]
   The CGI-I response was defined as having a score of 1 (very much improved) or 2 (much improved). 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. By definition, all CGI-I assessments were evaluated against baseline conditions.
9. Change From Baseline in the Generalized Anxiety Disorder 7-Item Scale (GAD-7) Total Score [ Time Frame: Baseline, Hour 60, Days 7, 14, 21 and 30 ]
   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.
10. Percentage of Participants With Treatment Emergent Adverse Event (TEAE) [ Time Frame: Up to approximately 37 days ]
    An Adverse Event (AE) is 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 (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 is 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.
11. Time to Change in Antidepressant Medication [ Time Frame: Up to approximately 37 days ]
    The time to first start or increase in the dose and time to first stop or decrease in the dose of any antidepressant medication.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Female participants between 18 and 45 years of age with PPD, defined as those who had a major depressive episode that began no earlier than the third trimester and no later than the first four weeks following delivery, as diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM), 4th Edition Axis I Disorders (SCID-I), a HAM-D total score of ≥20 and ≤25 at screening and Day 1 (prior to dosing), and who were ≤6 months postpartum at screening were eligible for enrollment.
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Participant either must have ceased lactating at screening; or if still lactating or actively breastfeeding at screening, agreed to temporarily cease giving breastmilk to their infant(s).
• 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 had a HAM-D total score of ≥20 and ≤25 at screening and Day 1 (prior to dosing).
• Participant was ≤ six months postpartum.
• Participant was amenable to intravenous therapy.

Key Exclusion Criteria:

• Active psychosis.
• Attempted suicide associated with index case of postpartum depression.
• Medical history of bipolar disorder.

Note: Other protocol-defined inclusion/exclusion criteria applied.

Contacts and Locations

Locations

United States, Arizona

Sage Investigational Site

Chandler, Arizona, United States, 85226

United States, Arkansas

Sage Investigational Site

Rogers, Arkansas, United States, 72758

United States, California

Sage Investigational Site

Lemon Grove, California, United States, 91945

Sage Investigational Site

Orange, California, United States, 92868

Sage Investigational Site

Ventura, California, United States, 93003

United States, Florida

Sage Investigational Site

Gainesville, Florida, United States, 32607

Sage Investigational Site

Miami, Florida, United States, 33147

Sage Investigational Site

Miramar, Florida, United States, 33027

Sage Investigational Site

Orlando, Florida, United States, 32807

Sage Investigational Site

Pensacola, Florida, United States, 32502

Sage Investigational Site

Pinellas Park, Florida, United States, 33782

United States, Georgia

Sage Investigational Site

Atlanta, Georgia, United States, 30331

United States, Illinois

Sage Investigational Site

Hoffman Estates, Illinois, United States, 60169

United States, Kansas

Sage Investigational Site

Wichita, Kansas, United States, 67226

United States, Kentucky

Sage Investigational Site

Edgewood, Kentucky, United States, 41017

Sage Investigational Site

Owensboro, Kentucky, United States, 42303

United States, Massachusetts

Sage Investigational Site

Boston, Massachusetts, United States, 02114

United States, Mississippi

Sage Investigational Site

Flowood, Mississippi, United States, 39232

United States, New Jersey

Sage Investigational Site

Marlton, New Jersey, United States, 08053

United States, New York

Sage Investigational Site

Glen Oaks, New York, United States, 11004

United States, North Carolina

Sage Investigational Site

Chapel Hill, North Carolina, United States, 27514

Sage Investigational Site

Charlotte, North Carolina, United States, 28211

Sage Investigational Site

Raleigh, North Carolina, United States, 27612

United States, Ohio

Sage Investigational Site

Columbus, Ohio, United States, 43210

Sage Investigational Site

Dayton, Ohio, United States, 45417

United States, Pennsylvania

Sage Investigational Site

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

Sage Investigational Site

Baytown, Texas, United States, 77521

Sage Investigational Site

Houston, Texas, United States, 77030

Sage Investigational Site

Houston, Texas, United States, 77058

Sage Investigational Site

Richardson, Texas, United States, 75080

Sage Investigational Site

San Antonio, Texas, United States, 78229

United States, Utah

Sage Investigational Site

Orem, Utah, United States, 84058

Sponsors and Collaborators

Sage Therapeutics

Investigators

• Study Director: Helen Colquhoun, MD; Sage Therapeutics

  Study Documents (Full-Text)

Documents provided by Sage Therapeutics:

Study Protocol  [PDF] March 16, 2017

Statistical Analysis Plan  [PDF] October 27, 2017

More Information

Additional Information:

Related Info 

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Meltzer-Brody S, Colquhoun H, Riesenberg R, Epperson CN, Deligiannidis KM, Rubinow DR, Li H, Sankoh AJ, Clemson C, Schacterle A, Jonas J, Kanes S. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. 2018 Sep 22;392(10152):1058-1070. doi: 10.1016/S0140-6736(18)31551-4. Epub 2018 Aug 31. Erratum In: Lancet. 2018 Sep 29;392(10153):1116.

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT02942017
• Other Study ID Numbers: 547-PPD-202 C
• First Posted: October 21, 2016
• Results First Posted: June 13, 2019
• Last Update Posted: January 28, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sage Therapeutics:

Moderate Postpartum Depression; SAGE-547

Additional relevant MeSH terms:

Depression, Postpartum; Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Brexanolone; Neurosteroids; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; GABA Modulators; GABA Agents