Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of SAGE-217 in Participants With Severe Postpartum Depression (PPD) (NCT NCT04442503)

Last Updated: 2023-11-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

200 participants

Primary outcome timeframe

Baseline and Day 15

Results posted on

2023-11-30

Participant Flow

Participants took part in study at 92 investigational sites in Spain, United Kingdom and United States from 8 June 2020 to 12 April 2022.

Participant milestones

Participant milestones
Measure	Placebo Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Study STARTED	101	99
Overall Study Number of Participants Received Investigational Product (IP)	98	98
Overall Study COMPLETED	86	84
Overall Study NOT COMPLETED	15	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Overall Study Adverse Event	1	1
Overall Study Lost to Follow-up	8	6
Overall Study Physician Decision	0	2
Overall Study Withdrawal by Subject	3	4
Overall Study Reason not Specified	0	1
Overall Study Randomized but not Treated	3	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=98 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.	Total n=196 Participants Total of all reporting groups
Age, Continuous	31.0 years STANDARD_DEVIATION 5.95 • n=5 Participants	30.0 years STANDARD_DEVIATION 5.90 • n=7 Participants	30.5 years STANDARD_DEVIATION 5.93 • n=5 Participants
Sex: Female, Male Female	98 Participants n=5 Participants	98 Participants n=7 Participants	196 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	42 Participants n=5 Participants	33 Participants n=7 Participants	75 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	56 Participants n=5 Participants	64 Participants n=7 Participants	120 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	18 Participants n=5 Participants	25 Participants n=7 Participants	43 Participants n=5 Participants
Race (NIH/OMB) White	69 Participants n=5 Participants	68 Participants n=7 Participants	137 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 15

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Change From Baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 Baseline	28.8 score on a scale Standard Deviation 2.34	28.6 score on a scale Standard Deviation 2.49
Change From Baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 Change from Baseline at Day 15	-11.4 score on a scale Standard Deviation 8.50	-15.6 score on a scale Standard Deviation 7.62

SECONDARY outcome

Timeframe: Baseline, Days 3, 28 and 45

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Change From Baseline in the 17-item HAM-D Total Score Change from Baseline at Day 3	-6.3 score on a scale Standard Deviation 6.78	-9.5 score on a scale Standard Deviation 7.40
Change From Baseline in the 17-item HAM-D Total Score Change from Baseline at Day 45	-14.8 score on a scale Standard Deviation 9.09	-17.7 score on a scale Standard Deviation 8.40
Change From Baseline in the 17-item HAM-D Total Score Baseline	28.8 score on a scale Standard Deviation 2.34	28.6 score on a scale Standard Deviation 2.49
Change From Baseline in the 17-item HAM-D Total Score Change from Baseline at Day 28	-13.5 score on a scale Standard Deviation 8.77	-16.3 score on a scale Standard Deviation 8.34

SECONDARY outcome

Timeframe: Baseline and Day 15

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Change From Baseline in Clinical Global Impressions - Severity Scale (CGI-S) Score Baseline	4.9 score on a scale Standard Deviation 0.58	5.0 score on a scale Standard Deviation 0.66
Change From Baseline in Clinical Global Impressions - Severity Scale (CGI-S) Score Change from Baseline at Day 15	-1.6 score on a scale Standard Deviation 1.38	-2.2 score on a scale Standard Deviation 1.51

SECONDARY outcome

Timeframe: Days 15 and 45

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Percentage of Participants With HAM-D Response Day 45	54.1 percentage of participants	61.9 percentage of participants
Percentage of Participants With HAM-D Response Day 15	38.9 percentage of participants	57.0 percentage of participants

SECONDARY outcome

Timeframe: Days 15 and 45

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Percentage of Participants With HAM-D Remission Day 15	16.7 percentage of participants	26.9 percentage of participants
Percentage of Participants With HAM-D Remission Day 45	29.4 percentage of participants	44.0 percentage of participants

SECONDARY outcome

Timeframe: Day 15

Population: 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.

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."

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=93 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response	46.7 percentage of participants	66.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Change From Baseline in Hamilton Rating Scale for Anxiety (HAM-A) Total Score Baseline	24.7 score on a scale Standard Deviation 5.96	24.4 score on a scale Standard Deviation 6.01
Change From Baseline in Hamilton Rating Scale for Anxiety (HAM-A) Total Score Change from Baseline at Day 15	-10.4 score on a scale Standard Deviation 7.15	-13.0 score on a scale Standard Deviation 8.19

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Baseline	35.0 score on a scale Standard Deviation 4.81	35.5 score on a scale Standard Deviation 5.37
Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Change from Baseline at Day 15	-14.1 score on a scale Standard Deviation 11.78	-19.9 score on a scale Standard Deviation 12.00

SECONDARY outcome

Timeframe: Baseline and Day 15

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Change From Baseline in HAM-D Subscale Core Subscale Baseline	47.6 score on a scale Standard Deviation 6.96	49.2 score on a scale Standard Deviation 6.79
Change From Baseline in HAM-D Subscale Change from Baseline in Core Subscale at Day 15	-20.4 score on a scale Standard Deviation 18.49	-27.7 score on a scale Standard Deviation 16.36
Change From Baseline in HAM-D Subscale Meier Subscale Baseline	56.3 score on a scale Standard Deviation 5.94	56.9 score on a scale Standard Deviation 6.11
Change From Baseline in HAM-D Subscale Anxiety Subscale Baseline	52.6 score on a scale Standard Deviation 9.23	51.2 score on a scale Standard Deviation 8.79
Change From Baseline in HAM-D Subscale Change from Baseline in Anxiety Subscale at Day 15	-20.4 score on a scale Standard Deviation 17.28	-26.0 score on a scale Standard Deviation 15.66
Change From Baseline in HAM-D Subscale Bech-6-Subscale Baseline	62.9 score on a scale Standard Deviation 6.14	63.7 score on a scale Standard Deviation 5.64
Change From Baseline in HAM-D Subscale Change from Baseline in Bech-6 Subscale at Day 15	-24.6 score on a scale Standard Deviation 21.37	-34.3 score on a scale Standard Deviation 19.61
Change From Baseline in HAM-D Subscale Change from Baseline in Meier Subscale at Day 15	-22.5 score on a scale Standard Deviation 18.99	-30.7 score on a scale Standard Deviation 17.23

SECONDARY outcome

Timeframe: Baseline, Days 3, 8,15, 21, 28 and 45

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score Change from Baseline at Day 3	-2.2 score on a scale Standard Deviation 4.50	-4.2 score on a scale Standard Deviation 5.34
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score Change from Baseline at Day 8	-6.0 score on a scale Standard Deviation 6.20	-8.9 score on a scale Standard Deviation 7.01
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score Change from Baseline at Day 15	-8.0 score on a scale Standard Deviation 6.41	-10.8 score on a scale Standard Deviation 7.18
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score Change from Baseline at Day 28	-9.4 score on a scale Standard Deviation 6.48	-11.6 score on a scale Standard Deviation 7.83
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score Change from Baseline at Day 45	-9.7 score on a scale Standard Deviation 7.40	-12.3 score on a scale Standard Deviation 7.87
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score Baseline	20.0 score on a scale Standard Deviation 4.15	21.1 score on a scale Standard Deviation 3.68
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score Change from Baseline at Day 21	-8.7 score on a scale Standard Deviation 6.65	-10.9 score on a scale Standard Deviation 6.72

SECONDARY outcome

Timeframe: Baseline, Days 3, 8,15, 21, 28 and 45

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score Change form Baseline at Day 3	-2.3 score on a scale Standard Error 0.462	-2.0 score on a scale Standard Error 0.456
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score Change from Baseline at Day 8	-5.9 score on a scale Standard Error 0.617	-7.7 score on a scale Standard Error 0.620
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score Change from Baseline at Day 15	-8.6 score on a scale Standard Error 0.652	-10.5 score on a scale Standard Error 0.651
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score Change from Baseline at Day 45	-9.8 score on a scale Standard Error 0.728	-11.7 score on a scale Standard Error 0.731
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score Change from Baseline at Day 21	-9.0 score on a scale Standard Error 0.655	-10.6 score on a scale Standard Error 0.651
Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score Change from Baseline at Day 28	-9.2 score on a scale Standard Error 0.692	-10.5 score on a scale Standard Error 0.703

SECONDARY outcome

Timeframe: Up to Day 45

Population: Safety Set included all participants who were administered IP.

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.

Outcome measures

Outcome measures
Measure	Placebo n=98 Participants Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 Participants Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)	53.1 percentage of participants	66.3 percentage of participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 52 other events

Deaths: 0 deaths

SAGE-217 50 mg

Serious events: 2 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=98 participants at risk Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 participants at risk Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
General disorders Oedema peripheral	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Psychiatric disorders Perinatal depression	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Vascular disorders Hypertension	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.

Other adverse events

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=98 participants at risk Participants received SAGE-217 matched-placebo capsules, orally, once daily for 14 days.	SAGE-217 50 mg n=98 participants at risk Participants received SAGE-217, 50 mg, capsules, orally, once daily for 14 days.
Nervous system disorders Somnolence	5.1% 5/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	26.5% 26/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Nervous system disorders Dizziness	10.2% 10/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	13.3% 13/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Nervous system disorders Sedation	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	11.2% 11/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Nervous system disorders Headache	13.3% 13/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	9.2% 9/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Nervous system disorders Memory impairment	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	3.1% 3/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Gastrointestinal disorders Diarrhea	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	6.1% 6/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Gastrointestinal disorders Nausea	6.1% 6/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	5.1% 5/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Gastrointestinal disorders Dry mouth	3.1% 3/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Infections and infestations COVID-19	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	5.1% 5/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Infections and infestations Urinary tract infection	4.1% 4/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	5.1% 5/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
General disorders Asthenia	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	4.1% 4/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
General disorders Fatigue	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	3.1% 3/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Psychiatric disorders Anxiety	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	3.1% 3/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	3.1% 3/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Investigations Blood triglycerides increased	4.1% 4/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Investigations Urine leukocyte esterase positive	3.1% 3/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Gastrointestinal disorders Abdominal pain	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Investigations Activated partial thromboplastin time prolonged	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Investigations Alanine aminotransferase increased	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Investigations Aspartate aminotransferase increased	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Musculoskeletal and connective tissue disorders Back pain	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Investigations Blood urine present	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Gastrointestinal disorders Constipation	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Gastrointestinal disorders Diarrhoea	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	6.1% 6/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Nervous system disorders Hypoaesthesia	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Musculoskeletal and connective tissue disorders Muscle twitching	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Investigations Nitrite urine present	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Investigations Prothrombin time prolonged	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Skin and subcutaneous tissue disorders Rash	1.0% 1/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Investigations Red blood cells urine positive	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Nervous system disorders Tremor	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Infections and infestations Upper respiratory tract infection	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.
Investigations White blood cells urine positive	2.0% 2/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.	0.00% 0/98 • From Baseline up to Day 45 Safety Set included all participants who were administered IP.