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A Study to Evaluate the Efficacy and Safety of SAGE-217 in Participants With Severe Postpartum Depression (PPD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04442503
Recruitment Status : Completed
First Posted : June 22, 2020
Results First Posted : June 22, 2023
Last Update Posted : November 30, 2023
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Depression, Postpartum
Interventions Drug: SAGE-217
Drug: Placebo
Enrollment 200
Recruitment Details Participants took part in study at 92 investigational sites in Spain, United Kingdom and United States from 8 June 2020 to 12 April 2022.
Pre-assignment Details  
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days. Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Period Title: Overall Study
Started 101 99
Number of Participants Received Investigational Product (IP) 98 98
Completed 86 84
Not Completed 15 15
Reason Not Completed
Adverse Event             1             1
Lost to Follow-up             8             6
Physician Decision             0             2
Withdrawal by Subject             3             4
Reason not Specified             0             1
Randomized but not Treated             3             1
Arm/Group Title Placebo SAGE-217 50 mg Total
Hide Arm/Group Description Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days. Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days. Total of all reporting groups
Overall Number of Baseline Participants 98 98 196
Hide Baseline Analysis Population Description
Safety Set included all participants who were administered Investigational product (IP).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 98 participants 98 participants 196 participants
31.0  (5.95) 30.0  (5.90) 30.5  (5.93)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 98 participants 98 participants 196 participants
Female
98
 100.0%
98
 100.0%
196
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 98 participants 98 participants 196 participants
Hispanic or Latino
42
  42.9%
33
  33.7%
75
  38.3%
Not Hispanic or Latino
56
  57.1%
64
  65.3%
120
  61.2%
Unknown or Not Reported
0
   0.0%
1
   1.0%
1
   0.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 98 participants 98 participants 196 participants
American Indian or Alaska Native
3
   3.1%
0
   0.0%
3
   1.5%
Asian
1
   1.0%
1
   1.0%
2
   1.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
18
  18.4%
25
  25.5%
43
  21.9%
White
69
  70.4%
68
  69.4%
137
  69.9%
More than one race
2
   2.0%
3
   3.1%
5
   2.6%
Unknown or Not Reported
5
   5.1%
1
   1.0%
6
   3.1%
1.Primary Outcome
Title Change From Baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15
Hide Description The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of 17 individual items related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), retardation, agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of the 17 individual items, ranges from 0 to 52; where a higher score indicates more depression. Negative change from baseline indicates improvement. Mixed Model for Repeated Measures (MMRM) was used for the analysis.
Time Frame Baseline and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set(FAS)=randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM for Anxiety(HAM-A), Montgomery Åsberg Depression Rating Scale(MADRS), Clinical Global Impressions-Severity(CGI-S), Edinburgh Postnatal Depression Scale(EPDS) and Patient Health Questionnaire(PHQ-9), or at least 1 post-baseline value of CGI-I. Number analyzed=number of participants with data available for analyses.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 97 98
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 97 participants 98 participants
28.8  (2.34) 28.6  (2.49)
Change from Baseline at Day 15 Number Analyzed 90 participants 93 participants
-11.4  (8.50) -15.6  (7.62)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -4.0
Confidence Interval (2-Sided) 95%
-6.3 to -1.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.16
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in the 17-item HAM-D Total Score
Hide Description The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of 17 individual items related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), retardation, agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of the 17 individual items, ranges from 0 to 52; where a higher score indicates more depression. Negative change from baseline indicates improvement. MMRM was used for the analysis.
Time Frame Baseline, Days 3, 28 and 45
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM-A, MADRS, CGI-S, EPDS and PHQ-9, or at least 1 post-baseline value of CGI-I. Number analyzed is the number of participants with data available for analysis.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 97 98
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 97 participants 98 participants
28.8  (2.34) 28.6  (2.49)
Change from Baseline at Day 3 Number Analyzed 96 participants 98 participants
-6.3  (6.78) -9.5  (7.40)
Change from Baseline at Day 28 Number Analyzed 85 participants 77 participants
-13.5  (8.77) -16.3  (8.34)
Change from Baseline at Day 45 Number Analyzed 85 participants 84 participants
-14.8  (9.09) -17.7  (8.40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.4
Confidence Interval (2-Sided) 95%
-5.4 to -1.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.999
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0203
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.9
Confidence Interval (2-Sided) 95%
-5.4 to -0.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.244
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 45
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0067
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.5
Confidence Interval (2-Sided) 95%
-6.0 to -1.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.277
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Clinical Global Impressions - Severity Scale (CGI-S) Score
Hide Description The CGI-S is a 7-point Likert scale to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who had the same diagnosis. A participant was assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7= extremely ill participants. A lower score indicates a better outcome. A negative change from baseline indicates improvement. MMRM was used for the analysis.
Time Frame Baseline and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM-A, MADRS, CGI-S, EPDS and PHQ-9, or at least 1 post-baseline value of CGI-I. Number analyzed is the number of participants with data available for analyses.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 97 98
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 97 participants 98 participants
4.9  (0.58) 5.0  (0.66)
Change from Baseline at Day 15 Number Analyzed 90 participants 93 participants
-1.6  (1.38) -2.2  (1.51)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0052
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-0.9 to -0.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.196
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With HAM-D Response
Hide Description The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of 17 individual items related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), retardation, agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of the 17 individual items, ranges from 0 to 52; where a higher score indicates more depression. Negative change from baseline indicates improvement. HAM-D response was defined as a ≥50% reduction in HAM-D total score from baseline.
Time Frame Days 15 and 45
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM-A, MADRS, CGI-S, EPDS and PHQ-9, or at least 1 post-baseline value of CGI-I. Number analyzed is the number of participants available for analyses. Percentages are rounded off to the nearest whole number.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 97 98
Measure Type: Number
Unit of Measure: percentage of participants
Day 15 Number Analyzed 90 participants 93 participants
38.9 57.0
Day 45 Number Analyzed 85 participants 84 participants
54.1 61.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0209
Comments P-value are from a generalized estimating equation (GEE) for binary response model, with factors for treatment, baseline HAMD-17 total score, baseline antidepressant use, assessment time point, and time-point-by treatment interaction.
Method GEE Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.020
Confidence Interval (2-Sided) 95%
1.112 to 3.670
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Day 45
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1661
Comments P-value are from a GEE for binary response model, with factors for treatment, baseline HAMD-17 total score, baseline antidepressant use, assessment time point, and time-point-by treatment interaction.
Method GEE Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.534
Confidence Interval (2-Sided) 95%
0.837 to 2.812
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With HAM-D Remission
Hide Description The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of 17 individual items related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), retardation, agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of the 17 individual items, ranges from 0 to 52; where a higher score indicates more depression. Negative change from baseline indicates improvement. HAM-D remission was defined as having a HAM-D total score of ≤7.
Time Frame Days 15 and 45
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM-A, MADRS, CGI-S, EPDS and PHQ-9, or at least 1 post-baseline value of CGI-I. Number analyzed is the number of participants with data available for analyses. Percentages are rounded off to the nearest whole number.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 97 98
Measure Type: Number
Unit of Measure: percentage of participants
Day 15 Number Analyzed 90 participants 93 participants
16.7 26.9
Day 45 Number Analyzed 85 participants 84 participants
29.4 44.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1110
Comments P-value are from a GEE for binary response model, with factors for treatment, baseline HAMD-17 total score, baseline antidepressant use, assessment time point, and time-point-by treatment interaction.
Method GEE Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.781
Confidence Interval (2-Sided) 95%
0.876 to 3.621
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Day 45
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0226
Comments P-value are from a GEE for binary response model, with factors for treatment, baseline HAMD-17 total score, baseline antidepressant use, assessment time point, and time-point-by treatment interaction.
Method GEE Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.083
Confidence Interval (2-Sided) 95%
1.108 to 3.915
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response
Hide Description The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The investigator rated the participant's total improvement whether or not it is due entirely to drug treatment. Response choices include 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 posttreatment assessments. By definition, all CGI-I assessments are evaluated against baseline conditions. CGI-I response was defined as having a CGI-I score of "very much improved" or "much improved."
Time Frame Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM-A, MADRS, CGI-S, EPDS and PHQ-9, or at least 1 post-baseline value of CGI-I. Overall number analyzed is the number of participants available for analyses. Number analyzed is the number of participants with data available for analyses.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 90 93
Measure Type: Number
Unit of Measure: percentage of participants
46.7 66.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0089
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.23
Confidence Interval (2-Sided) 95%
1.223 to 4.072
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Hamilton Rating Scale for Anxiety (HAM-A) Total Score
Hide Description The 14-item HAM-A was used to rate the severity of symptoms of anxiety. Each 14-items were defined by a series of symptoms, and measured both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The HAM-A total score was calculated as the sum of the 14 individual item scores. The scoring for HAM-A is calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56 where <17 indicated mild severity, 18 to 24, mild to moderate severity, and 25 to 30, moderate to severe severity. A negative change from baseline in HAM-A total score indicated improvement.
Time Frame Baseline and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM-A, MADRS, CGI-S, EPDS and PHQ-9, or at least 1 post-baseline value of CGI-I. Number of participants analyzed is the number of participants with data available for analyses.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 97 98
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 97 participants 98 participants
24.7  (5.96) 24.4  (6.01)
Change from Baseline at Day 15 Number Analyzed 90 participants 92 participants
-10.4  (7.15) -13.0  (8.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0235
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-4.2 to -0.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.98
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
Hide Description The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. It includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; and suicidal thoughts. Each item is rated on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change from baseline in MADRS total score indicated improvement.
Time Frame Baseline and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM-A, MADRS, CGI-S, EPDS and PHQ-9, or at least 1 post-baseline value of CGI-I. Overall number analyzed are the number of participants available for analysis. Number analyzed is the number of participants with data available for analyses.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 97 98
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 96 participants 98 participants
35.0  (4.81) 35.5  (5.37)
Change from Baseline at Day 15 Number Analyzed 89 participants 92 participants
-14.1  (11.78) -19.9  (12.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.1
Confidence Interval (2-Sided) 95%
-8.4 to -1.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.706
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in HAM-D Subscale
Hide Description 17-item HAM-D scale is used for severity of depression. HAM-D subscales: Core subscale(depressed mood, feelings of guilt, suicide, work and activities, and retardation/20x100; Anxiety subscale[anxiety(psychic and somatic), somatic symptoms (gastrointestinal and general), hypochondriasis, and insight loss of weight]/18x100; Bech-6 subscale(depressed mood, feelings of guilt, work and activities, retardation, anxiety psychic, and somatic symptoms general)/22x100; Maier score(depressed mood, feelings of guilt, work and activities, retardation, agitation, and anxiety psychic)/24x100. Each item was scored in range of 0 to 2 or 0 to 4 (0=none to 2 or 4=severe), higher score=more depression. 4 Subscale scores were calculated as sum of individual rating scores related to each subscale, divided by total possible score within subscale, multiplied by 100. Scores were transformed to scale of 0 to 100, with higher scores=more severe depression. Negative CFB=improvement. MMRM was used for analysis.
Time Frame Baseline and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM-A, MADRS, CGI-S, EPDS and PHQ-9, or at least 1 post-baseline value of CGI-I. Number analyzed is the number of participants with data available for analyses.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 97 98
Mean (Standard Deviation)
Unit of Measure: score on a scale
Core Subscale Baseline Number Analyzed 97 participants 98 participants
47.6  (6.96) 49.2  (6.79)
Change from Baseline in Core Subscale at Day 15 Number Analyzed 90 participants 93 participants
-20.4  (18.49) -27.7  (16.36)
Anxiety Subscale Baseline Number Analyzed 97 participants 98 participants
52.6  (9.23) 51.2  (8.79)
Change from Baseline in Anxiety Subscale at Day 15 Number Analyzed 90 participants 93 participants
-20.4  (17.28) -26.0  (15.66)
Bech-6-Subscale Baseline Number Analyzed 97 participants 98 participants
62.9  (6.14) 63.7  (5.64)
Change from Baseline in Bech-6 Subscale at Day 15 Number Analyzed 90 participants 93 participants
-24.6  (21.37) -34.3  (19.61)
Meier Subscale Baseline Number Analyzed 97 participants 98 participants
56.3  (5.94) 56.9  (6.11)
Change from Baseline in Meier Subscale at Day 15 Number Analyzed 90 participants 93 participants
-22.5  (18.99) -30.7  (17.23)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline in Core Subscale at Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0151
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.9
Confidence Interval (2-Sided) 95%
-10.6 to -1.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline in Anxiety Subscale at Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0123
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.7
Confidence Interval (2-Sided) 95%
-10.2 to -1.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.27
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline in Bech-6 Subscale at Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0040
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -8.6
Confidence Interval (2-Sided) 95%
-14.5 to -2.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline in Meier Subscale at Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0041
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -7.6
Confidence Interval (2-Sided) 95%
-12.7 to -2.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.609
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score
Hide Description The EPDS is a self-rated depressive symptom severity scale specific to the perinatal period which consists of 10 individual items. Each item is rated on a 4-point scale ranging from 0 to 3 points. The EPDS total score is calculated as the sum of the 10 individual item scores, ranging from 0 points to 30 points with a higher score indicating more depression. A negative change indicates improvement.
Time Frame Baseline, Days 3, 8,15, 21, 28 and 45
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM-A, MADRS, CGI-S, EPDS and PHQ-9, or at least 1 post-baseline value of CGI-I. Number analyzed is the number of participants with data available for analyses.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 97 98
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 97 participants 98 participants
20.0  (4.15) 21.1  (3.68)
Change from Baseline at Day 3 Number Analyzed 94 participants 97 participants
-2.2  (4.50) -4.2  (5.34)
Change from Baseline at Day 8 Number Analyzed 95 participants 93 participants
-6.0  (6.20) -8.9  (7.01)
Change from Baseline at Day 15 Number Analyzed 89 participants 91 participants
-8.0  (6.41) -10.8  (7.18)
Change from Baseline at Day 21 Number Analyzed 81 participants 84 participants
-8.7  (6.65) -10.9  (6.72)
Change from Baseline at Day 28 Number Analyzed 85 participants 76 participants
-9.4  (6.48) -11.6  (7.83)
Change from Baseline at Day 45 Number Analyzed 85 participants 84 participants
-9.7  (7.40) -12.3  (7.87)
11.Secondary Outcome
Title Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score
Hide Description The PHQ-9 is a self-rated depressive symptom severity scale to monitor severity over time for newly diagnosed participants or participants in current treatment for depression. Scoring was based on participants responses to 9 specific questions as follows: 0 = not at all; 1 = several days; 2 = more than half the days; and 3 = nearly every day. The score were calculated as the sum of the 9 individual item scores. The PHQ-9 total score was categorized as follows: 1 to 4 = minimal depression, 5 to 9 = mild depression, 10 to 14 = moderate depression, 15 to 19 = moderately severe depression; and 20 to 27 = severe depression. The PHQ-9 total score ranges from 1 to 27 with a higher score indicating more depression. A negative change from baseline indicates reduced depression. MMRM was used for the analysis.
Time Frame Baseline, Days 3, 8,15, 21, 28 and 45
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received any amount of IP and had valid baseline and at least one valid post-baseline total score in at least one of HAM-D, HAM-A, MADRS, CGI-S, EPDS and PHQ-9, or at least 1 post-baseline value of CGI-I. Number analyzed are the number of participants with data available for analysis.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 97 98
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change form Baseline at Day 3 Number Analyzed 94 participants 97 participants
-2.3  (0.462) -2.0  (0.456)
Change from Baseline at Day 8 Number Analyzed 95 participants 93 participants
-5.9  (0.617) -7.7  (0.620)
Change from Baseline at Day 15 Number Analyzed 90 participants 91 participants
-8.6  (0.652) -10.5  (0.651)
Change from Baseline at Day 21 Number Analyzed 81 participants 84 participants
-9.0  (0.655) -10.6  (0.651)
Change from Baseline at Day 28 Number Analyzed 85 participants 77 participants
-9.2  (0.692) -10.5  (0.703)
Change from Baseline at Day 45 Number Analyzed 85 participants 84 participants
-9.8  (0.728) -11.7  (0.731)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6912
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.0 to 1.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.649
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0410
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-3.5 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.874
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 15
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0444
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-3.7 to 0.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.922
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 21
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0811
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-3.4 to 0.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.924
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1846
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-3.3 to 0.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.987
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-217 50 mg
Comments Change from Baseline at Day 45
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0625
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-4.0 to 0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.031
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
Hide Description An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as an AE with onset after the start of IP, or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.
Time Frame Up to Day 45
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Hide Analysis Population Description
Safety Set included all participants who were administered IP.
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description:
Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.
Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Number of Participants Analyzed 98 98
Measure Type: Number
Unit of Measure: percentage of participants
53.1 66.3
Time Frame From Baseline up to Day 45
Adverse Event Reporting Description Safety Set included all participants who were administered IP.
 
Arm/Group Title Placebo SAGE-217 50 mg
Hide Arm/Group Description Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days. Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
All-Cause Mortality
Placebo SAGE-217 50 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/98 (0.00%)   0/98 (0.00%) 
Hide Serious Adverse Events
Placebo SAGE-217 50 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/98 (0.00%)   2/98 (2.04%) 
Gastrointestinal disorders     
Abdominal pain upper † 1  0/98 (0.00%)  1/98 (1.02%) 
General disorders     
Oedema peripheral † 1  0/98 (0.00%)  1/98 (1.02%) 
Psychiatric disorders     
Perinatal depression † 1  0/98 (0.00%)  1/98 (1.02%) 
Vascular disorders     
Hypertension † 1  0/98 (0.00%)  1/98 (1.02%) 
1
Term from vocabulary, MedDRA (24.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo SAGE-217 50 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   52/98 (53.06%)   64/98 (65.31%) 
Gastrointestinal disorders     
Diarrhea † 1  2/98 (2.04%)  6/98 (6.12%) 
Nausea † 1  6/98 (6.12%)  5/98 (5.10%) 
Dry mouth † 1  3/98 (3.06%)  2/98 (2.04%) 
Abdominal pain † 1  0/98 (0.00%)  2/98 (2.04%) 
Constipation † 1  2/98 (2.04%)  0/98 (0.00%) 
Diarrhoea † 1  2/98 (2.04%)  6/98 (6.12%) 
General disorders     
Asthenia † 1  1/98 (1.02%)  4/98 (4.08%) 
Fatigue † 1  1/98 (1.02%)  3/98 (3.06%) 
Infections and infestations     
COVID-19 † 1  0/98 (0.00%)  5/98 (5.10%) 
Urinary tract infection † 1  4/98 (4.08%)  5/98 (5.10%) 
Upper respiratory tract infection † 1  2/98 (2.04%)  0/98 (0.00%) 
Investigations     
Blood triglycerides increased † 1  4/98 (4.08%)  1/98 (1.02%) 
Urine leukocyte esterase positive † 1  3/98 (3.06%)  0/98 (0.00%) 
Activated partial thromboplastin time prolonged † 1  2/98 (2.04%)  1/98 (1.02%) 
Alanine aminotransferase increased † 1  2/98 (2.04%)  0/98 (0.00%) 
Aspartate aminotransferase increased † 1  2/98 (2.04%)  0/98 (0.00%) 
Blood urine present † 1  2/98 (2.04%)  0/98 (0.00%) 
Nitrite urine present † 1  2/98 (2.04%)  0/98 (0.00%) 
Prothrombin time prolonged † 1  2/98 (2.04%)  0/98 (0.00%) 
Red blood cells urine positive † 1  2/98 (2.04%)  0/98 (0.00%) 
White blood cells urine positive † 1  2/98 (2.04%)  0/98 (0.00%) 
Musculoskeletal and connective tissue disorders     
Myalgia † 1  0/98 (0.00%)  3/98 (3.06%) 
Back pain † 1  2/98 (2.04%)  1/98 (1.02%) 
Muscle twitching † 1  0/98 (0.00%)  2/98 (2.04%) 
Nervous system disorders     
Somnolence † 1  5/98 (5.10%)  26/98 (26.53%) 
Dizziness † 1  10/98 (10.20%)  13/98 (13.27%) 
Sedation † 1  1/98 (1.02%)  11/98 (11.22%) 
Headache † 1  13/98 (13.27%)  9/98 (9.18%) 
Memory impairment † 1  0/98 (0.00%)  3/98 (3.06%) 
Hypoaesthesia † 1  0/98 (0.00%)  2/98 (2.04%) 
Tremor † 1  0/98 (0.00%)  2/98 (2.04%) 
Psychiatric disorders     
Anxiety † 1  1/98 (1.02%)  3/98 (3.06%) 
Reproductive system and breast disorders     
Vaginal haemorrhage † 1  0/98 (0.00%)  2/98 (2.04%) 
Skin and subcutaneous tissue disorders     
Rash † 1  1/98 (1.02%)  2/98 (2.04%) 
1
Term from vocabulary, MedDRA (24.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Our agreement is subject to confidentiality but generally the PI can publish, for non-commercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: US Biogen Clinical Trial Center
Organization: Biogen
Phone: 866-633-4636
EMail: clinicaltrials@biogen.com
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT04442503    
Other Study ID Numbers: 217-PPD-301
2020-001424-34 ( EudraCT Number )
First Submitted: June 18, 2020
First Posted: June 22, 2020
Results First Submitted: April 11, 2023
Results First Posted: June 22, 2023
Last Update Posted: November 30, 2023