Trial Outcomes & Findings for A Study to Evaluate the Efficacy of SAGE-217 in the Treatment of Adult Participants With Major Depressive Disorder (NCT NCT03672175)

Results Overview

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 to 2 include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Total HAM-D score can range from 0 to 52, and higher scores indicate severe depression. A negative change from baseline indicates less depression.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

581 participants

Primary outcome timeframe

Baseline (BL), Day 15

Results posted on

2023-11-29

Participant Flow

Participants were enrolled in the study at 55 centers in the United States from 19 November 2018 to 17 March 2020.

A total of 1327 participants were screened of which 581 were randomized and 570 were dosed. This study consisted of up to a 28-day screening period, a 14-day treatment period, a 28-day follow-up (FU) period, and an extended FU period through Day 182 (6 months following the last dose).

Participant milestones

Participant milestones
Measure	SAGE-217 Matched Placebo Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.
Treatment Period (Days 1 to 14) STARTED	193	194	194
Treatment Period (Days 1 to 14) Safety Set	190	188	192
Treatment Period (Days 1 to 14) Modified Full Analysis Set (mFAS)	157	159	166
Treatment Period (Days 1 to 14) COMPLETED	182	180	185
Treatment Period (Days 1 to 14) NOT COMPLETED	11	14	9
FU Period (Days 15 to 42) STARTED	182	180	185
FU Period (Days 15 to 42) COMPLETED	178	170	178
FU Period (Days 15 to 42) NOT COMPLETED	4	10	7
Extended FU Period (Days 43 to 182) STARTED	178	170	178
Extended FU Period (Days 43 to 182) Extended FU Safety Set	129	127	131
Extended FU Period (Days 43 to 182) COMPLETED	141	131	141
Extended FU Period (Days 43 to 182) NOT COMPLETED	37	39	37

Reasons for withdrawal

Reasons for withdrawal
Measure	SAGE-217 Matched Placebo Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.
Treatment Period (Days 1 to 14) Withdrawal by Subject	6	6	4
Treatment Period (Days 1 to 14) Lost to Follow-up	2	2	3
Treatment Period (Days 1 to 14) Randomized but not Treated	3	6	2
FU Period (Days 15 to 42) Adverse Event	0	0	1
FU Period (Days 15 to 42) Lost to Follow-up	3	6	2
FU Period (Days 15 to 42) Withdrawal by Subject	1	4	4
Extended FU Period (Days 43 to 182) Adverse Event	5	3	3
Extended FU Period (Days 43 to 182) Lost to Follow-up	6	8	7
Extended FU Period (Days 43 to 182) Non-compliance with Study Drug	1	0	1
Extended FU Period (Days 43 to 182) Reason not Specified	3	4	3
Extended FU Period (Days 43 to 182) Physician Decision	4	0	2
Extended FU Period (Days 43 to 182) Withdrawal by Subject	18	24	21

Baseline Characteristics

mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SAGE-217 Matched Placebo n=190 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=188 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=192 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	Total n=570 Participants Total of all reporting groups
Age, Continuous	41.4 years STANDARD_DEVIATION 12.25 • n=190 Participants	42.5 years STANDARD_DEVIATION 12.10 • n=188 Participants	42.5 years STANDARD_DEVIATION 11.82 • n=192 Participants	42.1 years STANDARD_DEVIATION 12.04 • n=570 Participants
Sex: Female, Male Female	130 Participants n=190 Participants	131 Participants n=188 Participants	137 Participants n=192 Participants	398 Participants n=570 Participants
Sex: Female, Male Male	60 Participants n=190 Participants	57 Participants n=188 Participants	55 Participants n=192 Participants	172 Participants n=570 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	30 Participants n=190 Participants	35 Participants n=188 Participants	29 Participants n=192 Participants	94 Participants n=570 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	160 Participants n=190 Participants	153 Participants n=188 Participants	163 Participants n=192 Participants	476 Participants n=570 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=190 Participants	0 Participants n=188 Participants	0 Participants n=192 Participants	0 Participants n=570 Participants
Race/Ethnicity, Customized Race · White	118 Participants n=190 Participants	119 Participants n=188 Participants	108 Participants n=192 Participants	345 Participants n=570 Participants
Race/Ethnicity, Customized Race · Black or African-American	60 Participants n=190 Participants	64 Participants n=188 Participants	75 Participants n=192 Participants	199 Participants n=570 Participants
Race/Ethnicity, Customized Race · Asian	5 Participants n=190 Participants	4 Participants n=188 Participants	3 Participants n=192 Participants	12 Participants n=570 Participants
Race/Ethnicity, Customized Race · More than One Race	5 Participants n=190 Participants	1 Participants n=188 Participants	4 Participants n=192 Participants	10 Participants n=570 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=190 Participants	0 Participants n=188 Participants	2 Participants n=192 Participants	3 Participants n=570 Participants
Race/Ethnicity, Customized Race · American-Indian or Alaska Native	1 Participants n=190 Participants	0 Participants n=188 Participants	0 Participants n=192 Participants	1 Participants n=570 Participants
17-item HAM-D Total Score	25.8 score on a scale n=157 Participants • mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline.	25.8 score on a scale n=159 Participants • mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline.	25.9 score on a scale n=166 Participants • mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline.	25.8 score on a scale n=482 Participants • mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline.

PRIMARY outcome

Timeframe: Baseline (BL), Day 15

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses.

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 to 2 include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Total HAM-D score can range from 0 to 52, and higher scores indicate severe depression. A negative change from baseline indicates less depression.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in the 17-item HAM-D Total Score at Day 15	-11.1 score on a scale Standard Error 0.59	-11.5 score on a scale Standard Error 0.62	-12.5 score on a scale Standard Error 0.68	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 15

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses.

The CGI-S uses a 7-point Likert scale to rate the severity of the participant's illness relative to the clinician's past experience with participants who had the same diagnosis. Considering total clinical experience, 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. A higher score indicates extreme illness/more severity. A negative change from baseline indicates less severe illness.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=151 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=152 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Day 15	-1.5 score on a scale Standard Error 0.10	-1.6 score on a scale Standard Error 0.11	-1.7 score on a scale Standard Error 0.11	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 3, 8, 42, and 182

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 to 2 include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Total HAM-D score can range from 0 to 52, and higher scores indicate severe depression. A negative change from baseline indicates less depression.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=157 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=158 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=163 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in the 17-item HAM-D Total Score Change from Baseline at Day 3	-6.7 score on a scale Standard Error 0.46	-7.1 score on a scale Standard Error 0.48	-8.3 score on a scale Standard Error 0.47	—	—	—
Change From Baseline in the 17-item HAM-D Total Score Change from Baseline at Day 8	-7.8 score on a scale Standard Error 0.53	-8.4 score on a scale Standard Error 0.54	-9.9 score on a scale Standard Error 0.60	—	—	—
Change From Baseline in the 17-item HAM-D Total Score Change from Baseline at Day 42	-11.7 score on a scale Standard Error 0.64	-11.5 score on a scale Standard Error 0.70	-11.9 score on a scale Standard Error 0.67	—	—	—
Change From Baseline in the 17-item HAM-D Total Score Change from Baseline at Day 182	-13.2 score on a scale Standard Error 0.74	-13.4 score on a scale Standard Error 0.83	-13.9 score on a scale Standard Error 0.72	—	—	—

SECONDARY outcome

Timeframe: Days 15, 42, and 182

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

HAM-D response is defined as a ≥50% reduction in HAM-D score from baseline. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 to 2 include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Total HAM-D score can range from 0 to 52, and higher scores indicate severe depression.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants Achieving HAM-D Response Day 15	60 Participants	65 Participants	77 Participants	—	—	—
Number of Participants Achieving HAM-D Response Day 42	56 Participants	59 Participants	59 Participants	—	—	—
Number of Participants Achieving HAM-D Response Day 182	51 Participants	39 Participants	51 Participants	—	—	—

SECONDARY outcome

Timeframe: Days 15, 42, and 182

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

HAM-D remission is defined as HAM-D total score ≤7. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 to 2 include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Total HAM-D score can range from 0 to 52, and higher scores indicate severe depression.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants Achieving HAM-D Remission Day 15	33 Participants	35 Participants	48 Participants	—	—	—
Number of Participants Achieving HAM-D Remission Day 42	35 Participants	39 Participants	33 Participants	—	—	—
Number of Participants Achieving HAM-D Remission Day 182	32 Participants	29 Participants	34 Participants	—	—	—

SECONDARY outcome

Timeframe: Day 15

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses.

CGI-I response is defined as a CGI-I score of very much improved or much improved. The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition post-treatment. The Investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. Response choices included: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=151 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=152 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants Achieving Clinical Global Impression - Improvement (CGI-I) Response at Day 15	65 Participants	71 Participants	84 Participants	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 15

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses.

The 14-item HAM-A is used to rate the severity of symptoms of anxiety. Each of the 14 items is defined by a series of symptoms and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Scoring for HAM-A is calculated by assigning scores of 0 (not present) to 4 (very severe) to each item. Total HAM-A score is calculated as the sum of the 14 individual item scores with a total score range of 0 to 56, where the score of \<17 indicates mild severity, 18 to 24 indicates mild to moderate severity, and 25 to 30 indicates moderate to severe severity. A negative change from baseline indicates less severe symptoms.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=151 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at Day 15	-8.7 score on a scale Standard Error 0.49	-9.1 score on a scale Standard Error 0.54	-9.4 score on a scale Standard Error 0.53	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 15

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants 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. Each item is rated on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). Total MADRS score, calculated as the sum of the 10 individual items, ranges from 0 to 60 with a higher score indicating more depression. A negative change from baseline indicates less severe symptoms.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Day 15	-16.0 score on a scale Standard Error 0.93	-16.7 score on a scale Standard Error 1.00	-18.0 score on a scale Standard Error 1.03	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 42

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. HAM-D subscale scores are calculated as the sum of the items comprising each subscale. The core subscale score is the sum of the following symptom scores, scored in a range of 0 to 4: Depressed mood, feelings of guilt, suicide, work and activities, and retardation. Total HAM-D core subscale scores were transformed to a scale of 0 to 100. Higher scores indicate more severe depression. A negative change from baseline indicates less depression.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in HAM-D Core Subscale Score Change from Baseline at Day 42	-23.1 score on a scale Standard Error 1.36	-22.4 score on a scale Standard Error 1.44	-23.6 score on a scale Standard Error 1.40	—	—	—
Change From Baseline in HAM-D Core Subscale Score Change from Baseline at Day 15	-21.7 score on a scale Standard Error 1.33	-21.3 score on a scale Standard Error 1.31	-22.6 score on a scale Standard Error 1.38	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 42

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. HAM-D subscale scores are calculated as the sum of the items comprising each subscale. The anxiety subscale score is the sum of the following symptom scores: Anxiety (psychic and somatic) \[scored in a range of 0 to 4\], somatic symptoms (gastrointestinal and general) \[scored in a range of 0 to 2\], hypochondriasis \[scored in a range of 0 to 4\], and loss of weight \[scored in a range of 0 to 2\]. Total HAM-D anxiety subscale scores were transformed to a scale of 0 to 100. Higher scores indicate more severe depression/anxiety. A negative change from baseline indicates less depression.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in HAM-D Anxiety Subscale Score Change from Baseline at Day 15	-19.4 score on a scale Standard Error 1.19	-20.1 score on a scale Standard Error 1.28	-22.1 score on a scale Standard Error 1.30	—	—	—
Change From Baseline in HAM-D Anxiety Subscale Score Change from Baseline at Day 42	-22.0 score on a scale Standard Error 1.27	-20.7 score on a scale Standard Error 1.38	-21.7 score on a scale Standard Error 1.29	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 42

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. HAM-D subscale scores are calculated as the sum of the items comprising each subscale. The Bech-6 subscale score is the sum of the following symptom scores, scored in a range of 0 to 4: Depressed mood, feelings of guilt, work and activities, retardation, anxiety psychic, and somatic symptoms general. Total HAM-D Bech-6 subscale scores were transformed to a scale of 0 to 100. Higher scores indicate more severe depression. A negative change from baseline indicates less depression.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in HAM-D Bech-6 Subscale Score Change from Baseline at Day 15	-26.2 score on a scale Standard Error 1.57	-26.3 score on a scale Standard Error 1.62	-28.7 score on a scale Standard Error 1.70	—	—	—
Change From Baseline in HAM-D Bech-6 Subscale Score Change from Baseline at Day 42	-28.0 score on a scale Standard Error 1.66	-27.4 score on a scale Standard Error 1.77	-28.7 score on a scale Standard Error 1.70	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 42

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. HAM-D subscale scores are calculated as the sum of the items comprising each subscale. The Maier subscale score is the sum of the following symptom scores, scored in a range of 0 to 4: Depressed mood, feelings of guilt, work and activities, retardation, agitation, and anxiety psychic. Total HAM-D Maier subscale scores were transformed to a scale of 0 to 100. Higher scores indicate more severe depression. A negative change from baseline indicates less depression.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in HAM-D Maier Subscale Score Change from Baseline at Day 15	-23.4 score on a scale Standard Error 1.34	-23.1 score on a scale Standard Error 1.37	-25.9 score on a scale Standard Error 1.45	—	—	—
Change From Baseline in HAM-D Maier Subscale Score Change from Baseline at Day 42	-25.0 score on a scale Standard Error 1.42	-24.8 score on a scale Standard Error 1.53	-26.2 score on a scale Standard Error 1.49	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 42

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The 17-item HAM-D is used to rate the severity of depression in participants who were already diagnosed as depressed. The HAM-D comprises individual ratings of the following symptoms scored in a range of 0 to 2: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight (according to participant), and insight. The following symptoms are scored in a range of 0 to 4: Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. For each symptom, higher scores indicate more severe depression. A negative change from baseline indicates less depression. A positive change from baseline indicates more depression.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in HAM-D Individual Item Scores Depressed Mood: Change from Baseline at Day 15	-1.3 score on a scale Standard Error 0.10	-1.3 score on a scale Standard Error 0.10	-1.4 score on a scale Standard Error 0.10	—	—	—
Change From Baseline in HAM-D Individual Item Scores Depressed Mood: Change from Baseline at Day 42	-1.3 score on a scale Standard Error 0.10	-1.3 score on a scale Standard Error 0.11	-1.5 score on a scale Standard Error 0.10	—	—	—
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt: Change from Baseline at Day 15	-1.1 score on a scale Standard Error 0.08	-1.0 score on a scale Standard Error 0.07	-1.1 score on a scale Standard Error 0.07	—	—	—
Change From Baseline in HAM-D Individual Item Scores Feelings of Guilt: Change from Baseline at Day 42	-1.2 score on a scale Standard Error 0.08	-1.1 score on a scale Standard Error 0.08	-1.1 score on a scale Standard Error 0.08	—	—	—
Change From Baseline in HAM-D Individual Item Scores Suicide: Change from Baseline at Day 15	-0.3 score on a scale Standard Error 0.04	-0.3 score on a scale Standard Error 0.04	-0.3 score on a scale Standard Error 0.04	—	—	—
Change From Baseline in HAM-D Individual Item Scores Suicide: Change from Baseline at Day 42	-0.3 score on a scale Standard Error 0.04	-0.3 score on a scale Standard Error 0.04	-0.3 score on a scale Standard Error 0.04	—	—	—
Change From Baseline in HAM-D Individual Item Scores Insomnia Early - Early Night: Change from Baseline at Day 15	-0.8 score on a scale Standard Error 0.07	-0.9 score on a scale Standard Error 0.07	-0.8 score on a scale Standard Error 0.07	—	—	—
Change From Baseline in HAM-D Individual Item Scores Insomnia Early - Early Night: Change from Baseline at Day 42	-0.7 score on a scale Standard Error 0.07	-0.6 score on a scale Standard Error 0.07	-0.6 score on a scale Standard Error 0.08	—	—	—
Change From Baseline in HAM-D Individual Item Scores Insomnia Middle - Middle Night: Change from Baseline at Day 15	-0.8 score on a scale Standard Error 0.06	-0.9 score on a scale Standard Error 0.07	-0.9 score on a scale Standard Error 0.07	—	—	—
Change From Baseline in HAM-D Individual Item Scores Insomnia Middle - Middle Night: Change from Baseline at Day 42	-0.7 score on a scale Standard Error 0.07	-0.7 score on a scale Standard Error 0.07	-0.8 score on a scale Standard Error 0.07	—	—	—
Change From Baseline in HAM-D Individual Item Scores Insomnia Early Hours - Morning: Change from Baseline at Day 15	-0.4 score on a scale Standard Error 0.06	-0.5 score on a scale Standard Error 0.06	-0.6 score on a scale Standard Error 0.06	—	—	—
Change From Baseline in HAM-D Individual Item Scores Insomnia Early Hours - Morning: Change from Baseline at Day 42	-0.4 score on a scale Standard Error 0.07	-0.4 score on a scale Standard Error 0.07	-0.4 score on a scale Standard Error 0.07	—	—	—
Change From Baseline in HAM-D Individual Item Scores Work and Activities: Change from Baseline at Day 15	-1.2 score on a scale Standard Error 0.09	-1.2 score on a scale Standard Error 0.10	-1.3 score on a scale Standard Error 0.10	—	—	—
Change From Baseline in HAM-D Individual Item Scores Work and Activities: Change from Baseline at Day 42	-1.2 score on a scale Standard Error 0.10	-1.3 score on a scale Standard Error 0.10	-1.3 score on a scale Standard Error 0.10	—	—	—
Change From Baseline in HAM-D Individual Item Scores Retardation: Change from Baseline at Day 15	-0.5 score on a scale Standard Error 0.04	-0.5 score on a scale Standard Error 0.05	-0.5 score on a scale Standard Error 0.05	—	—	—
Change From Baseline in HAM-D Individual Item Scores Retardation: Change from Baseline at Day 42	-0.6 score on a scale Standard Error 0.04	-0.5 score on a scale Standard Error 0.05	-0.6 score on a scale Standard Error 0.04	—	—	—
Change From Baseline in HAM-D Individual Item Scores Agitation: Change from Baseline at Day 15	-0.5 score on a scale Standard Error 0.05	-0.5 score on a scale Standard Error 0.05	-0.6 score on a scale Standard Error 0.05	—	—	—
Change From Baseline in HAM-D Individual Item Scores Agitation: Change from Baseline at Day 42	-0.5 score on a scale Standard Error 0.05	-0.6 score on a scale Standard Error 0.06	-0.6 score on a scale Standard Error 0.05	—	—	—
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic: Change from Baseline at Day 15	-1.1 score on a scale Standard Error 0.09	-1.1 score on a scale Standard Error 0.09	-1.4 score on a scale Standard Error 0.08	—	—	—
Change From Baseline in HAM-D Individual Item Scores Anxiety Psychic: Change from Baseline at Day 42	-1.2 score on a scale Standard Error 0.09	-1.2 score on a scale Standard Error 0.09	-1.2 score on a scale Standard Error 0.09	—	—	—
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic: Change from Baseline at Day 15	-0.8 score on a scale Standard Error 0.07	-0.7 score on a scale Standard Error 0.06	-0.8 score on a scale Standard Error 0.07	—	—	—
Change From Baseline in HAM-D Individual Item Scores Anxiety Somatic: Change from Baseline at Day 42	-0.9 score on a scale Standard Error 0.08	-0.8 score on a scale Standard Error 0.07	-0.9 score on a scale Standard Error 0.07	—	—	—
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms Gastrointestinal: Change from Baseline at Day 15	-0.6 score on a scale Standard Error 0.06	-0.6 score on a scale Standard Error 0.06	-0.6 score on a scale Standard Error 0.06	—	—	—
Change From Baseline in HAM-D Individual Item Scores Somatic Symptoms Gastrointestinal: Change from Baseline at Day 42	-0.6 score on a scale Standard Error 0.06	-0.7 score on a scale Standard Error 0.07	-0.7 score on a scale Standard Error 0.06	—	—	—
Change From Baseline in HAM-D Individual Item Scores General Somatic Symptoms: Change from Baseline at Day 15	-0.6 score on a scale Standard Error 0.06	-0.7 score on a scale Standard Error 0.06	-0.7 score on a scale Standard Error 0.06	—	—	—
Change From Baseline in HAM-D Individual Item Scores General Somatic Symptoms: Change from Baseline at Day 42	-0.6 score on a scale Standard Error 0.07	-0.6 score on a scale Standard Error 0.07	-0.7 score on a scale Standard Error 0.07	—	—	—
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms: Change from Baseline at Day 15	-0.5 score on a scale Standard Error 0.07	-0.5 score on a scale Standard Error 0.06	-0.6 score on a scale Standard Error 0.07	—	—	—
Change From Baseline in HAM-D Individual Item Scores Genital Symptoms: Change from Baseline at Day 42	-0.5 score on a scale Standard Error 0.07	-0.5 score on a scale Standard Error 0.07	-0.6 score on a scale Standard Error 0.07	—	—	—
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis: Change from Baseline at Day 15	-0.4 score on a scale Standard Error 0.05	-0.4 score on a scale Standard Error 0.05	-0.5 score on a scale Standard Error 0.05	—	—	—
Change From Baseline in HAM-D Individual Item Scores Hypochondriasis: Change from Baseline at Day 42	-0.6 score on a scale Standard Error 0.04	-0.5 score on a scale Standard Error 0.05	-0.5 score on a scale Standard Error 0.05	—	—	—
Change From Baseline in HAM-D Individual Item Scores Loss of Weight: Change from Baseline at Day 15	-0.4 score on a scale Standard Error 0.05	-0.4 score on a scale Standard Error 0.05	-0.4 score on a scale Standard Error 0.06	—	—	—
Change From Baseline in HAM-D Individual Item Scores Loss of Weight: Change from Baseline at Day 42	-0.4 score on a scale Standard Error 0.06	-0.4 score on a scale Standard Error 0.05	-0.4 score on a scale Standard Error 0.06	—	—	—
Change From Baseline in HAM-D Individual Item Scores Insight: Change from Baseline at Day 15	0.0 score on a scale Standard Error 0.02	0.0 score on a scale Standard Error 0.02	-0.1 score on a scale Standard Error 0.01	—	—	—
Change From Baseline in HAM-D Individual Item Scores Insight: Change from Baseline at Day 42	0.0 score on a scale Standard Error 0.02	0.0 score on a scale Standard Error 0.01	0.0 score on a scale Standard Error 0.02	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 42

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The ISI is a validated questionnaire designed to assess the nature, severity, and impact of insomnia. The ISI uses a 5-point Likert scale to measure various aspects of insomnia severity (0=none, 1=mild, 2=moderate; 3=severe; 4=very severe), satisfaction with current sleep pattern (0=very satisfied, 1=satisfied, 2=moderately satisfied, 3=dissatisfied, 4=very dissatisfied), and various aspects of the impact of insomnia on daily functioning (0=not at all, 1=a little, 2=somewhat, 3=much, 4=very much). The ISI total score is calculated as the sum of the 7 individual item scores and the possible total score range is from 0 to 28, categorized as follows: 0 to 7=no clinically significant insomnia, 8 to 14=subthreshold insomnia, 15 to 21=clinical insomnia (moderate severity), and 22 to 28=clinical insomnia (severe). Higher scores indicate more severity. A negative change from baseline indicates less severe insomnia.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=141 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in Insomnia Severity Index (ISI) Total Score Change from Baseline at Day 15	-6.2 score on a scale Standard Error 0.55	-7.4 score on a scale Standard Error 0.58	-8.2 score on a scale Standard Error 0.58	—	—	—
Change From Baseline in Insomnia Severity Index (ISI) Total Score Change from Baseline at Day 42	-6.9 score on a scale Standard Error 0.64	-5.9 score on a scale Standard Error 0.60	-6.9 score on a scale Standard Error 0.62	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 28

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The Core Consensus Sleep Diary collected subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep) to derive sleep parameters, including sSL, sTST, and sWASO. The take-home participant sleep diary assessment was administered using an eDiary solution. The eDiary was captured using either a provisioned smartphone device or a bring-your-own-device solution, depending on the participant's preference. sTST is a derived parameter calculated as: Time of final awakening - (time when tried to sleep + time taken to fall asleep)-time of being awake after sleep onset. Negative change from baseline in sSL and sWASO indicates improvement. Positive change from baseline in sTST indicates improvement.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=129 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=138 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=143 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in Core Consensus Sleep Diary Parameters: Sleep Onset Latency (sSL), Wake After Sleep Onset (sWASO), and Total Sleep Time (sTST) Change from Baseline in sSL at Day 15	-12.2 minutes Standard Error 3.02	-14.4 minutes Standard Error 3.34	-20.1 minutes Standard Error 3.24	—	—	—
Change From Baseline in Core Consensus Sleep Diary Parameters: Sleep Onset Latency (sSL), Wake After Sleep Onset (sWASO), and Total Sleep Time (sTST) Change from Baseline in sSL at Day 28	-12.1 minutes Standard Error 4.26	-16.4 minutes Standard Error 3.73	-15.8 minutes Standard Error 4.77	—	—	—
Change From Baseline in Core Consensus Sleep Diary Parameters: Sleep Onset Latency (sSL), Wake After Sleep Onset (sWASO), and Total Sleep Time (sTST) Change from Baseline in sWASO at Day 15	-19.2 minutes Standard Error 2.87	-21.4 minutes Standard Error 3.00	-18.8 minutes Standard Error 4.28	—	—	—
Change From Baseline in Core Consensus Sleep Diary Parameters: Sleep Onset Latency (sSL), Wake After Sleep Onset (sWASO), and Total Sleep Time (sTST) Change from Baseline in sWASO at Day 28	-21.0 minutes Standard Error 3.68	-18.2 minutes Standard Error 3.18	-17.1 minutes Standard Error 4.57	—	—	—
Change From Baseline in Core Consensus Sleep Diary Parameters: Sleep Onset Latency (sSL), Wake After Sleep Onset (sWASO), and Total Sleep Time (sTST) Change from Baseline in sTST at Day 15	30.1 minutes Standard Error 7.92	54.2 minutes Standard Error 7.36	47.5 minutes Standard Error 7.99	—	—	—
Change From Baseline in Core Consensus Sleep Diary Parameters: Sleep Onset Latency (sSL), Wake After Sleep Onset (sWASO), and Total Sleep Time (sTST) Change from Baseline in sTST at Day 28	27.1 minutes Standard Error 9.93	41.2 minutes Standard Error 10.41	37.4 minutes Standard Error 9.36	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 28

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The Core Consensus Sleep Diary was used to collect subjective sleep parameter of sNAW. sNAW was calculated from the onset of persistent sleep until lights on. An awakening is defined as at least 2 consecutive epochs of wake. Individual awakenings were separated by at least 1 epoch of Stage N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) or rapid eye movement (REM) sleep. Lower ratings indicate better sleep quality and more refreshing/restorative quality of sleep.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=129 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=138 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=143 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in Core Consensus Sleep Diary Parameter: Number of Awakenings (sNAW) Change from Baseline at Day 15	-0.4 awakenings Standard Error 0.07	-0.5 awakenings Standard Error 0.07	-0.7 awakenings Standard Error 0.07	—	—	—
Change From Baseline in Core Consensus Sleep Diary Parameter: Number of Awakenings (sNAW) Change from Baseline at Day 28	-0.5 awakenings Standard Error 0.08	-0.3 awakenings Standard Error 0.09	-0.5 awakenings Standard Error 0.09	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 28

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The Core Consensus Sleep Diary collected subjective sleep parameters, including sleep quality (sSQ). The take-home participant sleep diary assessment was administered using an eDiary solution. The eDiary was captured using either a provisioned smartphone device or a bring-your-own-device solution, depending on the participant's preference. sSQ is rated on a 5-point Likert scale ranging from 1 (very poor) to 5 (very good). Higher ratings indicate better sleep quality. sSQ response is defined as having a sSQ score of very good or good.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=132 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=143 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=146 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in Core Consensus Sleep Diary Parameter: Number of Participants With Subjective Sleep Quality (sSQ) Response Change from Baseline at Day 15	36 Participants	35 Participants	32 Participants	—	—	—
Change From Baseline in Core Consensus Sleep Diary Parameter: Number of Participants With Subjective Sleep Quality (sSQ) Response Change from Baseline at Day 28	30 Participants	35 Participants	28 Participants	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 42

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

Participant's health was assessed using Patient-reported outcome (PRO) health related quality of life (HRQOL), SF-36v2 which is a 36-item measure of health status. It covers eight health dimensions including four physical health status domains (physical functioning, role participation with physical health problems, bodily pain, and general health) and four mental health status domains (vitality, social functioning, role participation with emotional health problems, and mental health). Two summary scores, physical component summary (PCS), and mental component summary (MCS) were produced by taking a weighted linear combination of the eight individual domains. The score range for PCS and MCS is 0 to 100 (100=highest level of functioning). Higher scores indicate a better state of health. A negative change from baseline indicates deteriorating health.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=140 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=153 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in the 36-item Short Form Survey Version 2 (SF-36v2) Physical and Mental Component Summary Scores PCS Score: Change from Baseline at Day 15	-0.9 score on a scale Standard Error 0.56	-1.2 score on a scale Standard Error 0.48	-1.4 score on a scale Standard Error 0.52	—	—	—
Change From Baseline in the 36-item Short Form Survey Version 2 (SF-36v2) Physical and Mental Component Summary Scores PCS Score: Change from Baseline at Day 42	-1.9 score on a scale Standard Error 0.63	-2.1 score on a scale Standard Error 0.50	-1.3 score on a scale Standard Error 0.58	—	—	—
Change From Baseline in the 36-item Short Form Survey Version 2 (SF-36v2) Physical and Mental Component Summary Scores MCS Score: Change from Baseline at Day 15	13.4 score on a scale Standard Error 1.15	14.6 score on a scale Standard Error 1.20	16.0 score on a scale Standard Error 1.31	—	—	—
Change From Baseline in the 36-item Short Form Survey Version 2 (SF-36v2) Physical and Mental Component Summary Scores MCS Score: Change from Baseline at Day 42	15.4 score on a scale Standard Error 1.21	15.9 score on a scale Standard Error 1.28	16.9 score on a scale Standard Error 1.30	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, and 42

Population: mFAS included all randomized participants with valid baseline HAM-D and at least 1 post-baseline HAM-D evaluation, with a total HAM-D score of at least 22 at baseline. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The PHQ-9 is a participant-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 each of the 9 questions, as follows: 0=not at all; 1=several days; 2=more than half the days; and 3=nearly every day. The PHQ-9 total score was 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. Higher scores indicate more severe depression. A negative change from baseline indicates reduced depression.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=139 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=152 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=149 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in the 9-item Patient Health Questionnaire (PHQ-9) Total Score Change from Baseline at Day 15	-7.1 score on a scale Standard Error 0.59	-7.3 score on a scale Standard Error 0.60	-8.3 score on a scale Standard Error 0.62	—	—	—
Change From Baseline in the 9-item Patient Health Questionnaire (PHQ-9) Total Score Change from Baseline at Day 42	-8.1 score on a scale Standard Error 0.61	-7.3 score on a scale Standard Error 0.59	-8.7 score on a scale Standard Error 0.60	—	—	—

SECONDARY outcome

Timeframe: Treatment period: Up to Day 14; FU period: Day 15 to 42

Population: Safety Set included all participants who were administered IP in treatment period. The AE data were collected and reported period-wise.

An adverse event (AE) is any untoward medical occurrence in a participant administered with 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, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. 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. A serious TEAE is defined as a TEAE that at any dose results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or results in a congenital abnormality or birth defect.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=190 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=188 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=192 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo n=190 Participants Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg n=188 Participants Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg n=192 Participants Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) and Serious TEAE in Treatment and FU Periods TEAE	77 Participants	78 Participants	93 Participants	46 Participants	44 Participants	46 Participants
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) and Serious TEAE in Treatment and FU Periods Serious TEAE	0 Participants	0 Participants	2 Participants	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Extended FU Period: Day 43 to 182

Population: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU Period. The AE data were collected and reported period-wise.

An adverse event (AE) is any untoward medical occurrence in a participant administered with 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, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. 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. A serious TEAE is defined as a TEAE that at any dose results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or results in a congenital abnormality or birth defect.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=129 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=127 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=131 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) and Serious TEAE in Extended FU Period TEAE	27 Participants	29 Participants	28 Participants	—	—	—
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) and Serious TEAE in Extended FU Period Serious TEAE	1 Participants	3 Participants	1 Participants	—	—	—

SECONDARY outcome

Timeframe: Treatment period: Up to Day 14; FU period: Day 15 to 42

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

Laboratory parameters include serum chemistry- Alanine aminotransferase: \>3x upper limit of normal (ULN); Alanine aminotransferase or aspartate aminotransferase: \>3x ULN; Bilirubin: \>1.5x ULN, \>2x ULN; Calcium: \<2.0 millimoles per liter (mmol/L); Gamma Glutamyl Transferase \[units per liter (U/L)\]: \>3xULN; Potassium: \>5.4 mmol/L; Sodium: \>150 mmol/L; Hematology- Hematocrit : Male \<0.385 liter/liter (L/L) and Female \<0.345 L/L and Male \>0.55 L/L and Female \>0.49 L/L; Hemoglobin: Male \<115 grams/liter (g/L) and Female \<100 g/L; Neutrophils: \<1.5 10\^9/L.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=190 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=188 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=192 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo n=190 Participants Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg n=188 Participants Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg n=192 Participants Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants With Clinically Significant Abnormalities in Laboratory Measures in Treatment and FU Periods	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Extended FU Period: Day 43 to 182

Population: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period.

Laboratory parameters include serum chemistry- Alanine aminotransferase: \>3x upper limit of normal (ULN); Alanine aminotransferase or aspartate aminotransferase: \>3x ULN; Bilirubin: \>1.5x ULN, \>2x ULN; Calcium: \<2.0 millimoles per liter (mmol/L); Gamma Glutamyl Transferase \[units per liter (U/L)\]: \>3xULN; Potassium: \>5.4 mmol/L; Sodium: \>150 mmol/L; Hematology- Hematocrit : Male \<0.385 liter/liter (L/L) and Female \<0.345 L/L and Male \>0.55 L/L and Female \>0.49 L/L; Hemoglobin: Male \<115 grams/liter (g/L) and Female \<100 g/L; Neutrophils: \<1.5 10\^9/L.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=129 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=127 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=131 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants With Clinically Significant Abnormalities in Laboratory Measures in Extended FU Period	0 Participants	0 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Treatment period: Up to Day 14; FU period: Day 15 to 42

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

Vital signs include supine and standing systolic blood pressure (SBP) \[millimeters of mercury (mmHg)\]: \<90, \>180, increase and decrease from baseline of \>=30; Supine and standing diastolic blood pressure (DBP) (mmHg): Increase and decrease from baseline \>=20; Standing heart rate (\>120 beats per minute); Orthostatic SBP (\>=20); Orthostatic DBP (\>=10); Orthostatic hypotension (SBP \>=20 and DBP \>=10, SBP \>=20 or DBP \>=10).

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=190 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=188 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=192 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo n=190 Participants Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg n=188 Participants Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg n=192 Participants Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants With Clinically Significant Vital Sign Abnormalities in Treatment and FU Periods	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Extended FU Period: Day 43 to 182

Population: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period.

Vital signs include supine and standing SBP \[mmHg\]: \<90, \>180, increase and decrease from baseline of \>=30; Supine and standing DBP (mmHg): Increase and decrease from baseline \>=20; Standing heart rate (\>120 beats per minute); Orthostatic SBP (\>=20); Orthostatic DBP (\>=10); Orthostatic hypotension (SBP \>=20 and DBP \>=10, SBP \>=20 or DBP \>=10).

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=129 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=127 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=131 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants With Clinically Significant Vital Sign Abnormalities in Extended FU Period	0 Participants	0 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Treatment period: Up to Day 14; FU period: Day 15 to 42

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

Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR, QRS, QT, and corrected QT interval by Fridericia \[QTcF\]) as well as any rhythm abnormalities were recorded. Criteria for clinically significant ECG abnormalities included QTcF interval (msec)- females: \>450 to 480, male: \>450 to 470, females: \>480 to 500, male: \>470 to 500 or \>500.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=190 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=188 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=192 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo n=190 Participants Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg n=188 Participants Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg n=192 Participants Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities in Treatment and FU Periods	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Extended FU Period: Day 43 to 182

Population: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period.

Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR, QRS, QT, and QTcF) as well as any rhythm abnormalities were recorded. Criteria for clinically significant ECG abnormalities included QTcF interval (msec)- females: \>450 to 480, male: \>450 to 470, females: \>480 to 500, male: \>470 to 500 or \>500.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=129 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=127 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=131 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants With Clinically Significant ECG Abnormalities in Extended FU Period	0 Participants	0 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Day 42

Population: Safety Set included all participants who were administered IP in treatment period. This outcome measure was planned to be assessed for all participants in the Safety Set by summarizing and reporting data for treatment and FU periods combined together as double-blind treatment period.

Suicidality was monitored during the study using the C-SSRS scale. The C-SSRS includes 'yes' or 'no' responses for 5 questions for assessment of suicidal ideation and behavior. Any suicidal behavior: When response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation: When response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=190 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=188 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=192 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants With Suicidal Ideation or Behavior Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) in Double-blind Treatment Period at Day 42	12 Participants	11 Participants	11 Participants	—	—	—

SECONDARY outcome

Timeframe: Day 182

Population: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period.

Suicidality was monitored during the study using the C-SSRS scale. The C-SSRS includes 'yes' or 'no' responses for 5 questions for assessment of suicidal ideation and behavior. Any suicidal behavior: When response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation: When response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=129 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=127 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=131 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Number of Participants With Suicidal Ideation or Behavior Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) in Extended FU Period at Day 182	9 Participants	6 Participants	3 Participants	—	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, 18, and 21

Population: Safety Set included all participants who were administered IP. Here, "Overall number of participants analyzed" is the number of participants with data available for analyses. "Number analyzed" is the number of participants evaluable for this outcome measure at specified time points.

The PWC-20 was used to monitor for the presence of potential withdrawal symptoms following discontinuation of SAGE-217. The PWC-20 was made up of a list of 20 symptoms (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue-lethargy-lack of energy, poor coordination, restlessness-agitation, diaphoresis, tremor-tremulousness, dizziness-lightheadedness, headaches, muscle aches or stiffness, weakness, increased acuity \[sound, smell, touch, pain\], paresthesia, difficulty concentrating and remembering, depersonalization-derealization) that were rated on a scale of 0 (not present) to 3 (severe). The PWC-20 total score was derived as the sum of individual item scores, which ranges from 0 (not present) to 60 (severe). Higher scores indicate more severe withdrawal. A negative change from baseline indicates less severe withdrawal.

Outcome measures

Outcome measures
Measure	SAGE-217 Matched Placebo n=169 Participants Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 20 mg n=175 Participants Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	SAGE-217 30 mg n=172 Participants Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.
Change From Baseline in the 20-item Physician Withdrawal Checklist (PWC-20) Total Score Change from Baseline at Day 15	-5.407 score on a scale Standard Deviation 7.0047	-5.370 score on a scale Standard Deviation 7.5424	-5.699 score on a scale Standard Deviation 7.7363	—	—	—
Change From Baseline in the 20-item Physician Withdrawal Checklist (PWC-20) Total Score Change from Baseline at Day 18	-6.128 score on a scale Standard Deviation 6.9928	-5.421 score on a scale Standard Deviation 7.0046	-5.917 score on a scale Standard Deviation 7.7158	—	—	—
Change From Baseline in the 20-item Physician Withdrawal Checklist (PWC-20) Total Score Change from Baseline at Day 21	-5.623 score on a scale Standard Deviation 7.2786	-6.136 score on a scale Standard Deviation 7.2765	-5.961 score on a scale Standard Deviation 7.0005	—	—	—

Adverse Events

Treatment Period: SAGE-217 Matched Placebo

Serious events: 0 serious events

Other events: 43 other events

Deaths: 0 deaths

Treatment Period: SAGE-217 20 mg

Serious events: 0 serious events

Other events: 53 other events

Deaths: 0 deaths

Treatment Period: SAGE-217 30 mg

Serious events: 2 serious events

Other events: 60 other events

Deaths: 0 deaths

FU Period: SAGE-217 Matched Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

FU Period: SAGE-217 20 mg

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

FU Period: SAGE-217 30 mg

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Extended FU Period: SAGE-217 Matched Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Extended FU Period: SAGE-217 20 mg

Serious events: 3 serious events

Other events: 0 other events

Deaths: 1 deaths

Extended FU Period: SAGE-217 30 mg

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Period: SAGE-217 Matched Placebo n=190 participants at risk Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	Treatment Period: SAGE-217 20 mg n=188 participants at risk Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	Treatment Period: SAGE-217 30 mg n=192 participants at risk Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo n=190 participants at risk Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg n=188 participants at risk Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg n=192 participants at risk Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.	Extended FU Period: SAGE-217 Matched Placebo n=129 participants at risk Participants who received SAGE-217 matched placebo during the treatment period were followed up through Day 182 (6 months following the last IP dose) as a part of the extended FU period.	Extended FU Period: SAGE-217 20 mg n=127 participants at risk Participants who received SAGE-217 20 mg during the treatment period were followed up through Day 182 (6 months following the last IP dose) as a part of the extended FU period.	Extended FU Period: SAGE-217 30 mg n=131 participants at risk Participants who received SAGE-217 30 mg during the treatment period were followed up through Day 182 (6 months following the last IP dose) as a part of the extended FU period.
Hepatobiliary disorders Bile duct stone	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.52% 1/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Psychiatric disorders Suicide attempt	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.52% 1/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Psychiatric disorders Agitation	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.53% 1/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Psychiatric disorders Delirium	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.53% 1/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Psychiatric disorders Drug abuse	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.53% 1/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Psychiatric disorders Suicidal ideation	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.53% 1/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Psychiatric disorders Depression	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.79% 1/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Psychiatric disorders Mania	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.78% 1/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Nervous system disorders Syncope	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.52% 1/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Nervous system disorders Toxic encephalopathy	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.53% 1/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.52% 1/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.52% 1/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.52% 1/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Infections and infestations Pneumonia	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.53% 1/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.53% 1/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Renal and urinary disorders Acute kidney injury	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.53% 1/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.53% 1/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Vascular disorders Hypertension	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.76% 1/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
General disorders Death	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.79% 1/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Skin and subcutaneous tissue disorders Diabetic foot	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.79% 1/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.

Other adverse events

Other adverse events
Measure	Treatment Period: SAGE-217 Matched Placebo n=190 participants at risk Participants self-administered SAGE-217 matched placebo capsules, orally, once daily in the evening with food for 14 days.	Treatment Period: SAGE-217 20 mg n=188 participants at risk Participants self-administered SAGE-217 20 mg capsules, orally, once daily in the evening with food for 14 days.	Treatment Period: SAGE-217 30 mg n=192 participants at risk Participants self-administered SAGE-217 30 mg capsules, orally, once daily in the evening with food for 14 days.	FU Period: SAGE-217 Matched Placebo n=190 participants at risk Participants who received SAGE-217 matched placebo during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 20 mg n=188 participants at risk Participants who received SAGE-217 20 mg during the treatment period were included in this group and followed up for 28 days.	FU Period: SAGE-217 30 mg n=192 participants at risk Participants who received SAGE-217 30 mg during the treatment period were included in this group and followed up for 28 days.	Extended FU Period: SAGE-217 Matched Placebo n=129 participants at risk Participants who received SAGE-217 matched placebo during the treatment period were followed up through Day 182 (6 months following the last IP dose) as a part of the extended FU period.	Extended FU Period: SAGE-217 20 mg n=127 participants at risk Participants who received SAGE-217 20 mg during the treatment period were followed up through Day 182 (6 months following the last IP dose) as a part of the extended FU period.	Extended FU Period: SAGE-217 30 mg n=131 participants at risk Participants who received SAGE-217 30 mg during the treatment period were followed up through Day 182 (6 months following the last IP dose) as a part of the extended FU period.
Nervous system disorders Headache	7.4% 14/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	11.2% 21/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	6.2% 12/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Nervous system disorders Dizziness	3.7% 7/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	7.4% 14/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	5.7% 11/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Nervous system disorders Somnolence	4.2% 8/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	5.9% 11/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	6.8% 13/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Nervous system disorders Sedation	3.2% 6/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	5.9% 11/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	4.7% 9/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Gastrointestinal disorders Diarrhoea	5.3% 10/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	5.9% 11/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	6.2% 12/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Gastrointestinal disorders Nausea	4.7% 9/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	5.3% 10/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	3.6% 7/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.
Gastrointestinal disorders Fatigue	2.6% 5/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	1.6% 3/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	6.8% 13/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/190 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/188 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/192 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/129 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/127 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.	0.00% 0/131 • Treatment period: Up to 14 days; FU period: Day 15 to 42; Extended FU Period: Day 43 to 182 Treatment and FU periods: Safety Set included all participants who were administered IP. FU period: Safety Set included all participants who were administered IP in treatment period. Extended FU period: Extended FU Safety Set included all participants in the Safety Set of treatment period who consented or reconsented to participate in the study in the 6-month FU period. The AE data were collected and reported period-wise.

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