Evaluate SAGE-547 in Female Participants With Severe Postpartum Depression

NCT02285504 | Completed Phase 2 Results

• 1 other identifier: 547-PPD-201
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label proof-of-concept study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of SAGE-547 Injection in adult female participants diagnosed with severe postpartum depression (PPD).

Conditions

Postpartum Depression

Keywords

Postpartum depression

Outcome Measures

Primary Outcomes (22)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  AEs were any untoward medical occurrences in a participant who received study treatment without regard to possibility of causal relationship. TEAEs were defined as AEs with onset after the start of SAGE-547 infusion, or any worsening of a pre-existing medical condition or AEs with onset after the start of SAGE-547 infusion and until 7 days after the end of infusion (Day 11). TESAEs were defined as AEs with onset after the start of SAGE-547 infusion, or any worsening of a pre-existing medical condition or AEs with onset after the start of SAGE-547 infusion and until 30 days after the end of infusion (Day 34).

  TEAEs: Up to Day 11, TESAEs: Up to Day 34

• Change From Baseline in Clinical Laboratory Measures: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT)

  Clinical laboratory evaluation included: Chemistry (ALT, AST, GGT) expressed in terms of units per liter (U/L). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measures: Carbon Dioxide (CO2), Sodium, Potassium and Chloride

  Clinical laboratory evaluation included: Chemistry (carbon dioxide \[CO2\], sodium, potassium and chloride) expressed in terms of millimoles/liter (mmol/L). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measures: Glucose, Total Bilirubin, Calcium, Blood Urea Nitrogen (BUN) and Creatinine

  Clinical laboratory evaluation included: Chemistry (glucose, total bilirubin, calcium, blood urea nitrogen \[BUN\] and creatinine) expressed in terms of milligrams/deciliter (mg/dL). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measures: Albumin, Total Protein and Hemoglobin

  Clinical laboratory evaluation included: Chemistry (albumin, total protein), Hematology and Coagulation (hemoglobin) expressed in terms of g/dL. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measure: Hematocrit

  Clinical laboratory evaluation included: Hematocrit expressed in terms of percentage. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measures: Platelet Count, White Blood Cells (WBC), Absolute Lymphocytes, Absolute Neutrophils, Absolute Basophils, Absolute Eosinophils, Absolute Monocytes

  Clinical laboratory evaluation included: Platelet count, white blood cells (WBC), absolute lymphocytes, absolute neutrophils, absolute basophils, absolute eosinophils, absolute monocytes expressed in terms of 10\^9 cells/L. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measure: Red Blood Cells (RBC)

  Clinical laboratory evaluation included: RBC expressed in terms of 10\^12 cells/L. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Volume (MCV)

  Clinical laboratory evaluation included: MCV expressed in terms of femtoliters (fL). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measure: Mean Corpuscular Hemoglobin (MCH)

  Clinical laboratory evaluation included: MCH expressed in terms of picogram (pg). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measure: Prothrombin Time/International Normalized Ratio (PT/INR)

  Clinical laboratory evaluation included: PT/INR expressed in terms of seconds. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measure: Potential of Hydrogen (pH)

  Clinical laboratory evaluation included: Urinalysis (pH). The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Clinical Laboratory Measure: Specific Gravity

  Clinical laboratory evaluation included: Urinalysis (specific gravity) expressed in terms of ratio. The data was collected at time-points on Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs).

  Baseline, Days 2 (at 24 hrs), 3 (at 48 hrs) and 4 (at 84 hrs)

• Change From Baseline in Vital Sign: Blood Pressure

  Vital sign parameters included supine systolic blood pressure (SBP), supine diastolic blood pressure (DBP), standing systolic blood pressure and standing diastolic blood pressure expressed in terms of millimeters of mercury (mmHg). The data was collected at time-points on Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs).

  Baseline, Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs)

• Change From Baseline in Vital Sign: Heart Rate

  Vital sign parameter included heart rate expressed in terms of beats per minute (bpm). The data was collected at time-points on Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs).

  Baseline, Day 1 (12 hrs) Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs)

• Change From Baseline in Vital Sign: Body Temperature

  Vital sign parameter included temperature expressed in terms of degree Celsius. The data was collected at time-points on Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs).

  Baseline, Day 1 (12 hrs) Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs)

• Change From Baseline in Vital Sign: Respiratory Rate

  Vital sign parameter included respiratory rate expressed in terms of breaths per minute. The data was collected at time-points on Day 1 (12 hrs), Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs).

  Baseline, Day 1 (12 hrs) Day 2 (at 24 and 36 hrs), on Day 3 (at 48 and 60 hrs), and Day 4 (at 72 and 84 hrs)

• Change From Baseline in Electrocardiogram (ECG) Parameters: QT Interval, PR Interval, QTc Interval, and QRS Duration

  ECGs parameters included QT interval, PR interval, QTc interval, QRS duration expressed in terms of milliseconds (msec).

  Baseline, Day 4 (at 84 hrs)

• Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate

  ECGs parameter included heart rate expressed in terms of beats per minute (bpm).

  Baseline, Day 4 (at 84 hrs)

• Number of Participants With Physical Examination Findings

  Physical examinations included body weight, height, body mass index (BMI) and assessment of body systems (e.g., head, eyes, ears, nose, throat, lungs, abdomen, and extremities) as well as cognitive and mental health examinations (components of the neurological and psychiatric examinations, respectively).

  At Day 4

• Number of Participants With Concomitant Medication Usage

  Concomitant medications are other prescription medications, over the counter (OTC) drugs or dietary supplements that a study participant takes in addition to the drug under investigation.

  Baseline up to Day 11

• Number of Participants With Suicidal Ideation and Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

  C-SSRS scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicidal ideation and behavior, and a post-baseline evaluation that focuses on suicidality since the last study visit. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, (with score range from 1 to 5, higher score indicates more severity). The data was collected at time-points: Pre-infusion (Day 1 prior to dosing), Post-infusion (any time after the start of infusion on Day 1 up to 84 hrs).

  Pre-infusion (Day 1 prior to dosing), Post-infusion (any time after the start of infusion on Day 1 up to 84 hrs)

Secondary Outcomes (9)

• Maximum Plasma Concentration (Cmax) of SAGE-547

  Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose

• Time to Maximum Plasma Concentration (Tmax) of SAGE-547

  Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose

• Area Under the Concentration-Time Curve From Start of the Infusion Until the Time of the Last Sample (AUCall) of SAGE-547

  Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, 60, and 72 hrs post-dose

• Area Under the Concentration-Time Curve From Time Zero to 60 Hours (AUC0-60) of SAGE-547

  Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, 24, 36, 40, 44, 48, and 60 hrs post-dose

• Area Under the Concentration-Time Curve in 24 Hours (AUC24) of SAGE-547

  Predose (0 hrs), and 0.5, 1, 2, 3, 4, 6, 12, and 24 hrs post-dose

Study Arms (1)

SAGE-547

EXPERIMENTAL

Participants received SAGE-547 intravenous injection over 60 hours (including 12-hour titration infusion of 21.5 micrograms per kilogram per hour \[mcg/kg/hr\] \[4 hrs\], 43 mcg/kg/hr \[4 hrs\] and 64.5 mcg/kg/hr \[4 hrs\] on Day 1, followed by 13 to 48 hrs \[36 hrs\] maintenance infusion of 86 mcg/kg/hr from Day 1 to 3, followed by a 12-hr taper infusion of 64.5 mcg/kg/hr \[49 - 52 hrs\], 43 mcg/kg/hr \[53 - 56 hrs\] and 21.5 mcg/kg/hr \[57 - 60 hrs\] on Day 3).

Drug: SAGE-547

Interventions

SAGE-547 DRUG

Intravenous injection

SAGE-547

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult females, 18-45 years old who experienced a major depressive episode in the postpartum period beginning within the first 4 weeks following delivery
• Participant has ceased lactating, or if still lactating has already fully and permanently weaned their infant; if still actively breastfeeding, participant must agree to cease giving breast milk to their infant prior to study entry

You may not qualify if:

• Recent history or active clinically significant manifestations of metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, musculoskeletal, dermatological, urogenital, or eyes, ears, or nose and throat (EENT) disorders
• Active psychosis
• Medical history of seizures

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead

Study Sites (1)

Sage Investigational Site

Chapel Hill, North Carolina, 27514, United States

Location

Related Links

• Sage Therapeutics

MeSH Terms

Conditions

Depression, Postpartum

Interventions

brexanolone

Condition Hierarchy (Ancestors)

Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Monitor
• Organization: Sage Therapeutics

info@sagerx.com

(617) 299-8380

Study Officials

• Stephen J Kanes, MD, PhD

  Sage Therapeutics

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2014
• First Posted: November 7, 2014
• Study Start: January 7, 2015
• Primary Completion: June 5, 2015
• Study Completion: June 5, 2015
• Last Updated: September 15, 2025
• Results First Posted: December 2, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)