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

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ClinicalTrials.gov Identifier: NCT02942004
Recruitment Status : Completed
First Posted : October 21, 2016
Results First Posted : June 13, 2019
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
Sage Therapeutics

Tracking Information
First Submitted Date  ICMJE October 20, 2016
First Posted Date  ICMJE October 21, 2016
Results First Submitted Date  ICMJE April 11, 2019
Results First Posted Date  ICMJE June 13, 2019
Last Update Posted Date June 13, 2019
Actual Study Start Date  ICMJE August 1, 2016
Actual Primary Completion Date September 24, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2019)
Change From Baseline at 60 Hours in the 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 20, 2016)
Effect of SAGE-547 on depressive symptoms in subjects with severe postpartum depression compared to placebo injection as measured by the change from baseline in Hamilton Rating Scale for Depression (HAMD) total score [ Time Frame: 3 Days ]
Change History Complete list of historical versions of study NCT02942004 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2019)
  • 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.
  • 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.
  • 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.
  • Percentage of Participants With HAM-D Remission [ Time Frame: Hour 60, Days 7 and 30 ]
    The 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.
  • 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.
  • Change From Baseline in HAM-D Individual Item Scores [ Time Frame: Baseline, Hour 2, Hour 4, Hour 8, Hour 12, Hour 24, Hour 36, Hour 48, Hour 60, Hour 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.
  • 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.
  • Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response [ Time Frame: Hour 60, Days 7 and 30 ]
    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. By definition, all CGI-I assessments were evaluated against baseline conditions. CGI-I response was defined as having a score of 1 (very much improved) or 2 (much improved).
  • 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.
  • Percentage of Participants With Treatment-Emergent Adverse Events [ 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 treatment-emergent AE (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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2016)
  • Safety and tolerability of SAGE-547 compared with placebo as measured by the change from baseline in the incidence of AEs, vital signs, clinical laboratory evaluations, and ECG parameters [ Time Frame: 30 Days ]
  • Safety of SAGE-547 compared to placebo as measured by the change from baseline in suicidal ideation and behavior assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) score [ Time Frame: 30 Days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Efficacy and Safety of SAGE-547 in Participants With Severe Postpartum Depression (547-PPD-202B)
Official Title  ICMJE 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
Brief Summary The purpose of this study was to determine if SAGE-547 Injection infused intravenously at up to 90 micrograms per kilogram per hour (μg/kg/h) for 60 hours reduces depressive symptoms in participants with severe postpartum depression (PPD) compared to placebo injection as assessed by the change from baseline in Hamilton Rating Scale for Depression (HAM-D) total score.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Postpartum Depression
Intervention  ICMJE
  • Drug: Placebo
    Intravenous infusion of matching placebo for either SAGE-547 60 μg/kg/h or 90 μg/kg/h.
  • Drug: SAGE-547 60 μg/kg/h
    Intravenous infusion of SAGE-547.
  • Drug: SAGE-547 90 μg/kg/h
    Intravenous infusion of SAGE-547.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Participants received infusion rates equivalent to either the 60 micrograms per kilogram per hour (μg/kg/h) or 90 μg/kg/h group.
    Intervention: Drug: Placebo
  • Experimental: SAGE-547 60 μg/kg/h
    Participants received a 4-hour titration period of 30 μg/kg/h (0 to 4 hours), then 60 μg/kg/h (4 to 56 hours), followed by a taper to 30 μg/kg/h (56 to 60 hours).
    Intervention: Drug: SAGE-547 60 μg/kg/h
  • 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).
    Intervention: Drug: SAGE-547 90 μg/kg/h
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 10, 2017)
138
Original Estimated Enrollment  ICMJE
 (submitted: October 20, 2016)
60
Actual Study Completion Date  ICMJE October 19, 2017
Actual Primary Completion Date September 24, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Participants 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) from just prior to receiving study drug through nine days (Day 12) after the end of the infusion
  • Participants 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 ≥26 at screening and Day 1 (prior to dosing)
  • Participant was ≤6 months postpartum at screening
  • Participant was amenable to IV therapy

Key Exclusion Criteria:

  • Active psychosis
  • Attempted suicide associated with index case of postpartum depression
  • Medical history of bipolar disorders, schizophrenia, and/or schizoaffective disorder.

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

Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Female participants with postpartum depression defined as those who 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 Diagnostic and Statistical Manual of Mental Disorders (DSM), 4th Edition Axis I Disorders (SCID-I), a Hamilton Rating Scale for Depression (HAM-D) total score of ≥26 at screening and Day 1 (prior to dosing), and who were ≤6 months postpartum at screening.
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries New Zealand
 
Administrative Information
NCT Number  ICMJE NCT02942004
Other Study ID Numbers  ICMJE 547-PPD-202 B
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sage Therapeutics
Study Sponsor  ICMJE Sage Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Helen Colquhoun, MD Sage Therapeutics
PRS Account Sage Therapeutics
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP