A Study to Evaluate the Safety, Tolerability, and Efficac... | NCT03771664

A Study to Evaluate the Safety, Tolerability, and Efficac... | NCT03771664 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out [polysomnography (PSG)] on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.	Drug: Placebo
SAGE-217	Experimental	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 milligrams (mg) capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.	Drug: SAGE-217

Name	Type	Description	Arm Group Labels	Other Names
SAGE-217	Drug	Administered as capsules.	SAGE-217
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Average Change From Baseline in Sleep Efficiency (SE) as Assessed by Polysomnogram (PSG) at Days 13 and 14	Sleep Efficiency (SE) is the percentage of time in bed spent asleep, determined during an 8-hour overnight PSG recording. The PSG measures the physiological process of sleep by monitoring body functions including brain waves, eye movements, muscle activity or skeletal muscle activation, heart rhythm, blood oxygen saturation, and breathing functions. Stages of sleep include rapid eye movement (REM), non-rapid eye movement (NREM), NREM stage 1 (N1), NREM stage 2 (N2), and NREM stage 3 (N3), scored through evaluation of the electroencephalogram (EEG) signal. The average of 2 nights' PSG measurements at Days 13 and 14 is reported in this outcome measure.	Baseline and Days 13, 14

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Wake After Sleep Onset (WASO) From Persistent Sleep Onset to Lights-on (Final Wake Time)	WASO is the total wake time (in minutes) calculated from persistent sleep onset to lights-on (final wake time). In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) WASO and in each quarter (for the each 2-hour duration) WASO of the 8-hour PSG recording is reported.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Sage Investigational Site		Little Rock	Arkansas	72211	United States
Sage Investigational Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out [polysomnography (PSG)] on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 18, 2019	Aug 31, 2022

Type	Comment	Reasons
Adverse Event		FG0001 subjects FG0010 subjects
Lost to Follow-up		FG0001 subjects FG0010 subjects
Withdrawal by Participant		FG0001 subjects FG0014 subjects
Randomized but not Treated		FG0000 subjects FG0011 subjects

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
BG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00042.0± 11.60 BG00144.6± 12.50 BG00243.3± 12.06

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00031 BG00128 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0007 BG00113 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Race

Title	Measurements
White	BG00030 BG00131 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Average Change From Baseline in Sleep Efficiency (SE) as Assessed by Polysomnogram (PSG) at Days 13 and 14

Sleep Efficiency (SE) is the percentage of time in bed spent asleep, determined during an 8-hour overnight PSG recording. The PSG measures the physiological process of sleep by monitoring body functions including brain waves, eye movements, muscle activity or skeletal muscle activation, heart rhythm, blood oxygen saturation, and breathing functions. Stages of sleep include rapid eye movement (REM), non-rapid eye movement (NREM), NREM stage 1 (N1), NREM stage 2 (N2), and NREM stage 3 (N3), scored through evaluation of the electroencephalogram (EEG) signal. The average of 2 nights' PSG measurements at Days 13 and 14 is reported in this outcome measure.

Full analysis set (FAS) included all randomized participants who received at least 1 dose of double-blind investigational product (IP) with valid baseline and at least one post-baseline efficacy evaluation. Number analyzed signifies the number of participants with data available for analyses at the specified time point.

Posted

Mean

Standard Deviation

percentage of time asleep

Baseline and Days 13, 14

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Units	Counts
Participants	OG00043 OG00143

Title

Denominators

Categories

Baseline

- ParticipantsOG00043
- ParticipantsOG00143

Title	Measurements
	OG00067.702± 14.9367

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.1537	Average change from baseline in SE was analyzed by analysis of covariance (ANCOVA) with explanatory (treatment, baseline antidepressant use, baseline SE) and response variables [change from baseline in sleep efficiency at Day 14 (EODBT)].	Least Square (LS) Mean Difference	3.2	Standard Error of the Mean	2.23	2-Sided	95	-1.2	7.7					Superiority

Secondary

Change From Baseline in Wake After Sleep Onset (WASO) From Persistent Sleep Onset to Lights-on (Final Wake Time)

WASO is the total wake time (in minutes) calculated from persistent sleep onset to lights-on (final wake time). In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) WASO and in each quarter (for the each 2-hour duration) WASO of the 8-hour PSG recording is reported.

FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.

Posted

Least Squares Mean

Standard Error

minutes

Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217

Secondary

Change From Baseline in Total Sleep Time (TST)

TST is the duration of total sleep time (NREM + REM) (in minutes) from lights off to lights on during PSG recording. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) TST and in each quarter (for the each 2-hour duration) TST of the 8-hour PSG recording is reported.

Posted

Least Squares Mean

Standard Error

minutes

Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217

Secondary

Change From Baseline in Latency to Persistent Sleep (LPS)

LPS is duration in minutes from lights off to the first epoch of 20 consecutive non-wake epochs.

Posted

Least Squares Mean

Standard Error

minutes

Baseline and Day 14 (EODBT)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Change From Baseline in Number of Awakenings (NAW)

NAW 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 REM sleep.

Posted

Least Squares Mean

Standard Error

awakenings

Baseline and Day 14 (EODBT)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Change From Baseline in Mean Duration of Awakenings

An awakening is defined as at least 2 consecutive epochs of wake. Mean duration of awakenings is an arithmetic mean calculated as the sum of duration of all awakenings (in minutes) divided by the number of awakenings. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) mean duration of awakenings and in each quarter (for the each 2-hour duration) mean duration of awakenings is reported.

Posted

Least Squares Mean

Standard Error

minutes

Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001

Secondary

Change From Baseline in Duration of Stage N1, N2, N3, and REM Sleep (in Minutes)

The change in duration (minutes) of NREM sleep stages: N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep time from lights off to lights on during PSG recording was reported.

Posted

Least Squares Mean

Standard Error

minutes

Baseline and Day 14 (EODBT)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Change From Baseline in Percentage of N1, N2, N3 Stages, and REM Sleep Duration

The change from baseline in duration of sleep time (percentage) of NREM sleep stages N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep was reported. Duration of sleep time was calculated from lights off to lights on during PSG recording.

Posted

Least Squares Mean

Standard Error

percentage of sleep time

Baseline and Day 14 (EODBT)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Change From Baseline in Latency to the First Period and Each Subsequent Period (Periods 2, 3, 4) of REM Sleep

Latency to REM sleep (REML) for first period is the number of non-REM epochs in terms of minutes (stages N1 [light sleep], N2 [also fairly light, with sudden increases in brain wave frequency known as sleep spindles], N3 [slow wave or deep sleep]) from LPS to the first epoch of REM sleep. REML for second and subsequent REM periods is the number of non-REM and REM epochs in terms of minutes (stages N1, N2, N3, and REM) from LPS to the first epoch of the 2nd REM period, or subsequent REM period.

FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation.

Posted

Least Squares Mean

Standard Error

minutes

Baseline and Day 14 (EODBT)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Change From Baseline in REM Density

REM density is the total number of REMs divided by the total duration of REM sleep in hours during time in bed (TIB).

Posted

Least Squares Mean

Standard Error

number of REM per hour

Baseline and Day 14 (EODBT)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Change From Baseline in REM Activity (REMA)

REMA is the total number of REMs during REM sleep, observed on the electrooculographic (EOG) channels of the PSG. The rapid eye movements must be at least 25 microvolts (uV) in amplitude.

Posted

Least Squares Mean

Standard Error

number of REM

Baseline and Day 14 (EODBT)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Change From Baseline in Insomnia Severity Index (ISI) Score

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 = neutral, 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 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 severe insomnia.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 15

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Change From Baseline in Consensus Sleep Diary - Core (CSD-C) Parameters

The CSD-C collects 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). Sleep parameters including subjective sleep latency (sSL), subjective TST (sTST), subjective WASO (sWASO), and subjective sleep quality (sSQ), were derived from the CSD-C responses. Change from baseline in sSL, sTST and sWASO was reported in this outcome measure.

Posted

Least Squares Mean

Standard Error

minutes

Baseline and Day 15

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217

Secondary

Change From Baseline in CSD-C Parameter: Subjective Sleep Quality (sSQ)

The CSD-C collects 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). Sleep parameters including sSL, sTST, sWASO, and sSQ, were derived from the CSD-C responses. Change from baseline in sSQ was reported in this outcome measure. Sleep quality is rated on a 5-point Likert scale ranging from 1 (very poor) to 5 (very good). Higher ratings indicate better sleep quality.

Posted

Mean

Standard Deviation

units on a scale

Baseline and Day 15

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217

Secondary

Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale

The severity of illness for each participant was rated using the CGI-S on a 7-point Likert scale with a total score range of 1-7 where a higher score represented a worse outcome. The participants were rated 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. In this study, the CGI-S was assessed based on the severity of insomnia disorder.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 15

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217

Secondary

Mean Score of the Clinical Global Impression - Improvement (CGI-I) Scale

The overall improvement in the participant's condition was assessed using CGI-I on a 7-point Likert scale with a total score range of 0-7 where a higher score represented a worse outcome. The participants were rated as: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. In this study, the CGI-I was assessed based on the improvement of insomnia disorder.

Posted

Mean

Standard Deviation

score on a scale

Day 15

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217

Secondary

Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score

The 17-item HAM-D was used to rate the severity of depression in participants who were already diagnosed as depressed. The 17-item HAM-D comprises individual ratings related to the following symptoms: Depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; Impaired ability to concentrate; Decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. Higher scores indicate severe depression.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 15

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Change From Baseline in the 9-item Patient Health Questionnaire (PHQ-9) Score

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 is based on responses to specific 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 severe depression.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 15

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) is any untoward medical occurrence in a clinical trial participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs after the first administration of double-blind study drug or placebo. SAE is any untoward medical occurrence 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, results in a congenital abnormality or birth defect.

Safety set included all participants who received at least 1 dose of double-blind study drug.

Posted

Count of Participants

Participants

From first dose of drug up to last follow-up visit (approximately 72 days)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Number of Participants With Potentially Clinically Significant Vital Signs

Potentially clinically significant vital signs reported 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).

Safety set included all participants who received at least 1 dose of double-blind study drug.

Posted

Count of Participants

Participants

Screening up to last follow-up visit (approximately 72 days)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities

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.

Safety set included all participants who received at least 1 dose of double-blind study drug.

Posted

Count of Participants

Participants

Screening up to last follow-up visit (approximately 72 days)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities

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 potentially 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.

Safety set included all participants who received at least 1 dose of double-blind study drug.

Posted

Count of Participants

Participants

Screening up to last follow-up visit (approximately 72 days)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Secondary

Number of Participants With Suicidal Ideation and Suicidal Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS)

C-SSRS scale was used to monitor suicidality. 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.

Safety set included all participants who received at least 1 dose of double-blind study drug.

Posted

Count of Participants

Participants

Screening up to last follow-up visit (approximately 72 days)

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
OG001	SAGE-217

Secondary

Change From Baseline in the Withdrawal Symptoms as Measured by the Physician Withdrawal Checklist (PWC-20) Total Score

The PWC-20 was used to monitor for the presence of potential withdrawal symptoms following discontinuation of IP. It consists 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 by the investigator on a scale of 0 (not present) to 3 (severe). The total score was derived as the sum of individual item scores, which ranges from 0 to 60. Higher scores indicate severe withdrawal. The total scores of PWC-20 were reported in this outcome measure.

Safety set included all participants who received at least 1 dose of double-blind study drug. Overall number of participants analyzed signifies the number of participants with data available for analyses for this outcome measure. Number analyzed signifies the number of participants with data available for analyses at the specified time point.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Days 18, 22, 28, 35 and 42

ID	Title	Description
OG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.	0	43	1	43	18	43
EG001	SAGE-217	Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.	0	43	1	43	17	43

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Focal dyscognitive seizures	Nervous system disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected43 at risk EG0011 affected43 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment		EG0001 affected43 at risk EG0010 affected43 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Somnolence	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected43 at risk EG0016 affected43 at risk
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected43 at risk EG0015 affected43 at risk
Dizziness	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected43 at risk EG0014 affected43 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0009 affected43 at risk EG0013 affected43 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0002 affected43 at risk EG0013 affected43 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected43 at risk EG0013 affected43 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0006 affected43 at risk EG0012 affected43 at risk

Title

Denominators

Categories

Change From Baseline in WASO for Overall Duration

Title	Measurements
	OG000-7.0± 5.87 OG001-20.0± 5.85

Change From Baseline in WASO in Quarter 1

Title	Measurements
	OG000-1.5± 1.23 OG001-1.6± 1.18

Change From Baseline in WASO in Quarter 2

Title	Measurements
	OG000-1.3± 2.33 OG001-5.6± 2.33

Change From Baseline in WASO in Quarter 3

Title	Measurements
	OG0003.1± 2.89 OG001-3.9± 2.90

Change From Baseline in WASO in Quarter 4

Title	Measurements
	OG000-4.9± 3.09 OG001-11.0± 3.11

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Change from baseline (BL) in overall WASO	ANCOVA	0.1126	Change from BL in overall WASO was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	-13.0	Standard Error of the Mean	8.07	2-Sided	95	-29.0	3.1	Superiority
OG000 OG001	Change from BL in WASO in quarter 1	ANCOVA	0.9819	Change from BL in WASO was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	0.0	Standard Error of the Mean	1.63	2-Sided	95	-3.3	3.2	Superiority
OG000 OG001	Change from BL in WASO in quarter 2	ANCOVA	0.1838	Change from BL in WASO was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	-4.3	Standard Error of the Mean	3.19	2-Sided	95	-10.6	2.1	Superiority
OG000 OG001	Change from BL in WASO in quarter 3	ANCOVA	0.0797	Change from BL in WASO was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, baseline PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	-7.1	Standard Error of the Mean	3.97	2-Sided	95	-15.0	0.9	Superiority
OG000 OG001	Change from BL in WASO in quarter 4	ANCOVA	0.1559	Change from BL in WASO was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, baseline PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	-6.1	Standard Error of the Mean	4.24	2-Sided	95	-14.5	2.4	Superiority

Title

Denominators

Categories

Change From Baseline in TST for Overall Duration

Title	Measurements
	OG00012.5± 7.73 OG00128.2± 7.69

Change From Baseline in TST in Quarter 1

Title	Measurements
	OG0002.4± 4.00 OG0017.1± 4.01

Change From Baseline in TST in Quarter 2

Title	Measurements
	OG0004.7± 3.02 OG0018.5± 3.03

Change From Baseline in TST in Quarter 3

Title	Measurements
	OG000-2.7± 2.93 OG0013.3± 2.94

Change From Baseline in TST in Quarter 4

Title	Measurements
	OG0005.0± 3.10 OG00111.5± 3.12

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Change from BL in overall TST	ANCOVA	0.1441	Change from BL in TST was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	15.8	Standard Error of the Mean	10.67	2-Sided	95	-5.5	37.0	Superiority
OG000 OG001	Change from BL in TST in quarter 1	ANCOVA	0.3951	Change from BL in TST was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	4.7	Standard Error of the Mean	5.47	2-Sided	95	-6.2	15.6	Superiority
OG000 OG001	Change from BL in TST in quarter 2	ANCOVA	0.3705	Change from BL in TST was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BLPSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	3.7	Standard Error of the Mean	4.16	2-Sided	95	-4.5	12.0	Superiority
OG000 OG001	Change from BL in TST in quarter 3	ANCOVA	0.1412	Change from BL in TST was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	6.0	Standard Error of the Mean	4.04	2-Sided	95	-2.0	14.0	Superiority
OG000 OG001	Change from BL in TST in quarter 4	ANCOVA	0.1298	Change from BL in TST was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	6.5	Standard Error of the Mean	4.24	2-Sided	95	-2.0	15.0	Superiority

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.7526	Change from BL in LPS was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	-2.5	Standard Error of the Mean	7.87	2-Sided	95	-18.2	13.2					Superiority

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.6769	Change from BL in NAW was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	-0.3	Standard Error of the Mean	0.83	2-Sided	95	-2.0	1.3					Superiority

Title

Denominators

Categories

Change From Baseline in Mean Duration of Awakenings in Overall

Title	Measurements
	OG000-0.3± 1.23 OG001-3.3± 1.24

Change From Baseline in Mean Duration of Awakenings in Quarter 1

Title	Measurements
	OG000-1.2± 0.80 OG001-2.1± 0.77

Change From Baseline in Mean Duration of Awakenings in Quarter 2

Title	Measurements
	OG0001.2± 2.21 OG001-2.3± 2.22

Change From Baseline in Mean Duration of Awakenings in Quarter 3

Title	Measurements
	OG000-0.5± 2.43 OG001-4.0± 2.46

Change From Baseline in Mean Duration of Awakenings in Quarter 4

Title	Measurements
	OG000-1.8± 0.49 OG001-2.3± 0.50

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG001	Change from BL in mean duration of awakenings (MDA) in total	ANCOVA	0.0824	Change from BL in MDA was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	-3.0	Standard Error of the Mean	1.70	2-Sided	95	-6.4	0.4	Superiority
OG000 OG001	Change from BL in MDA in quarter 1	ANCOVA	0.4269	Change from BL in MDA was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	-0.9	Standard Error of the Mean	1.07	2-Sided	95	-3.0	1.3	Superiority
OG000 OG001	Change from BL in MDA in quarter 2	ANCOVA	0.2482		LS Mean Difference	-3.5	Standard Error of the Mean	3.02	2-Sided	95	-9.5	2.5	Superiority	Change from BL in MDA was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).
OG000 OG001	Change from BL in MDA in quarter 3	ANCOVA	0.3076	Change from BL in MDA was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	-3.4	Standard Error of the Mean	3.34	2-Sided	95	-10.1	3.2	Superiority
OG000 OG001	Change from BL in MDA in quarter 4	ANCOVA	0.4491	Change from BL in MDA was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	-0.5	Standard Error of the Mean	0.68	2-Sided	95	-1.9	0.8	Superiority

Title

Denominators

Categories

Change From Baseline in Duration of Stage N1 Sleep

Title	Measurements
	OG000-0.3± 1.78 OG0010.1± 1.83

Change From Baseline in Duration of Stage N2 Sleep

Title	Measurements
	OG00013.1± 5.90 OG00131.7± 5.95

Change From Baseline in Duration of Stage N3 Sleep

Title	Measurements
	OG000-0.4± 4.08 OG0014.5± 4.09

Change From Baseline in Duration of REM Sleep

Title	Measurements
	OG0000.7± 3.46 OG001-9.5± 3.46

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Change from BL in duration of stage (DS) N1 sleep	ANCOVA	0.8724	Change from BL in DS N1 sleep was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	0.4	Standard Error of the Mean	2.47	2-Sided	95	-4.5	5.3	Superiority
OG000 OG001	Change from BL in DS N2 sleep	ANCOVA	0.0238	Change from BL in DS N2 sleep was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	18.6	Standard Error of the Mean	8.08	2-Sided	95	2.5	34.7	Superiority
OG000 OG001	Change from BL in DS N3 sleep	ANCOVA	0.3863	Change from BL in DS N3 sleep was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	4.9	Standard Error of the Mean	5.62	2-Sided	95	-6.3	16.1	Superiority
OG000 OG001	Change from BL in duration of REM sleep	ANCOVA	0.0320	Change from BL in REM sleep duration was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14(EODBT)].	LS Mean Difference	-10.2	Standard Error of the Mean	4.69	2-Sided	95	-19.6	-0.9	Superiority

Title

Denominators

Categories

Change From Baseline in Percentage of Stage N1 Sleep

Title	Measurements
	OG000-0.9± 0.59 OG001-1.0± 0.59

Change From Baseline in Percentage of Stage N2 Sleep

Title	Measurements
	OG0001.6± 1.13 OG0014.3± 1.14

Change From Baseline in Percentage of Stage N3 Sleep

Title	Measurements
	OG000-0.7± 1.10 OG0010.5± 1.11

Change From Baseline in Percentage of REM Sleep

Title	Measurements
	OG000-0.1± 0.78 OG001-3.9± 0.79

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Change from BL in percentage of stage (PS) N1 sleep time	ANCOVA	0.9524	Change from BL in PS N1 sleep time was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score;Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	0.0	Standard Error of the Mean	0.80	2-Sided	95	-1.7	1.6	Superiority
OG000 OG001	Change from BL in PS N2 sleep time	ANCOVA	0.0930	Change from BL in PS N2 sleep time was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	2.6	Standard Error of the Mean	1.55	2-Sided	95	-0.5	5.7	Superiority
OG000 OG001	Change from BL in PS N3 sleep time	ANCOVA	0.4427	Change from BL in PS N3 sleep time was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).	LS Mean Difference	1.2	Standard Error of the Mean	1.52	2-Sided	95	-1.9	4.2	Superiority
OG000 OG001	Change from BL in percentage (%) of REM sleep time	ANCOVA	0.0006	Change from BL in % of REM sleep duration was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].	LS Mean Difference	-3.8	Standard Error of the Mean	1.06	2-Sided	95	-5.9	-1.7	Superiority

Title

Denominators

Categories

Change From Baseline in Latency to the First REM Period

Title	Measurements
	OG0003.0± 9.17 OG00136.6± 9.17

Change From Baseline in Latency to the Second REM Period

Title	Measurements
	OG000-1.6± 8.34 OG00141.5± 8.16

Change From Baseline in Latency to the Third REM Period

Title	Measurements
	OG000-3.3± 8.79 OG00134.9± 8.33

Change From Baseline in Latency to the Fourth REM Period

Title	Measurements
	OG00019.2± 15.42 OG00145.2± 13.88

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Change from BL in latency to the first REM period	ANCOVA	0.0083	Change from BL in latency to first REM period was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].	LS Mean Difference	33.7	Standard Error of the Mean	12.42	2-Sided	95	8.9	58.4	Superiority
OG000 OG001	Change from BL in latency to the second REM period	ANCOVA	0.0002	Change from BL in latency to second REM period was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].	LS Mean Difference	43.2	Standard Error of the Mean	10.95	2-Sided	95	21.3	65.0	Superiority
OG000 OG001	Change from BL in latency to the third REM period	ANCOVA	0.0009	Change from BL in latency to third REM period was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].	LS Mean Difference	38.2	Standard Error of the Mean	10.99	2-Sided	95	16.2	60.2	Superiority
OG000 OG001	Change from BL in latency to the fourth REM period	ANCOVA	0.0899	Change from BL in latency to fourth REM period was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].	LS Mean Difference	26.0	Standard Error of the Mean	14.84	2-Sided	95	-4.3	56.3	Superiority

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.0004	Change from BL in REM density was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].	LS Mean Difference	-171.1	Standard Error of the Mean	46.06	2-Sided	95	-262.9	-79.4					Superiority

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		<0.0001	Change from BL in REMA was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, baseline PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].	LS Mean Difference	-288.0	Standard Error of the Mean	68.81	2-Sided	95	-425.1	-151.0					Superiority

Title

Denominators

Categories

Change From Baseline in sTST

Title	Measurements
	OG00039.9± 10.59 OG00150.3± 10.76

Change From Baseline in sWASO

Title	Measurements
	OG000-16.5± 4.72 OG001-27.4± 4.76

Change From Baseline in sSL

Title	Measurements
	OG000-15.7± 5.26 OG001-9.1± 5.31

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Change from BL in sTST	MMRM	0.4814	Change from BL in sTST was analyzed by Mixed Model Repeated Measures (MMRM) with treatment baseline antidepressant use, baseline CSD-C value, assessment time point, and time point-by-treatment interaction as fixed effects.	LS Mean Difference	10.4	Standard Error of the Mean	14.65	2-Sided	95	-18.8	39.5	Superiority
OG000 OG001	Change from BL in sWASO	MMRM	0.0964	Change from BL in sWASO was analyzed by MMRM with treatment baseline antidepressant use, baseline CSD-C value, assessment time point, and time point-by-treatment interaction as fixed effects.	LS Mean Difference	-10.9	Standard Error of the Mean	6.45	2-Sided	95	-23.7	2.0	Superiority
OG000 OG001	Change from BL in sSL	MMRM	0.3672	Change from BL in sSL was analyzed by MMRM with treatment baseline antidepressant use, baseline CSD-C value, assessment time point, and time point-by-treatment interaction as fixed effects.	LS Mean Difference	6.6	Standard Error of the Mean	7.32	2-Sided	95	-7.9	21.2	Superiority

Title

Denominators

Categories

Supine SBP (mmHg): <90

Title	Measurements
	OG0001 OG0010

Supine SBP (mmHg): Decrease From Baseline of >= 30

Title	Measurements
	OG0003 OG0012

Supine SBP (mmHg): Increase From Baseline of >= 30

Title	Measurements
	OG0001 OG0012

Standing SBP (mmHg): <90

Title	Measurements
	OG0001 OG0012

Standing SBP (mmHg): >180

Title	Measurements
	OG0000 OG0011

Standing SBP (mmHg): Decrease From Baseline of >= 30

Title	Measurements
	OG0003 OG0012

Standing SBP (mmHg): Increase From Baseline of >= 30

Title	Measurements
	OG0002 OG0013

Supine DBP (mmHg): Decrease From Baseline of >= 20

Title	Measurements
	OG0002 OG0013

Supine DBP (mmHg): Increase From Baseline of >= 20

Title	Measurements
	OG0001 OG0011

Standing DBP (mmHg): Decrease From Baseline of >= 20

Title	Measurements
	OG0001 OG0012

Standing DBP (mmHg): Increase From Baseline of >= 20

Title	Measurements
	OG0001 OG0014

Standing Heart Rate (beats per minute): >120

Title	Measurements
	OG0001 OG0010

Orthostatic SBP: >= 20

Title	Measurements
	OG0007 OG0015

Orthostatic DBP: >= 10

Title	Measurements
	OG0009 OG0013

Orthostatic Hypotension: SBP>=20 and DBP>=10

Title	Measurements
	OG0002 OG0012

Orthostatic Hypotension: SBP>=20 or DBP>=10

Title	Measurements
	OG00014 OG0017

Title

Denominators

Categories

Alanine Aminotransferase: >3x ULN

Title	Measurements
	OG0000 OG0013

Alanine Aminotransferase or Aspartate Aminotransferase: >3x ULN

Title	Measurements
	OG0000 OG0013

Bilirubin: >1.5x ULN

Title	Measurements
	OG0000 OG0011

Bilirubin: >2x ULN

Title	Measurements
	OG0000 OG0011

Calcium: <2.0 mmol/L

Title	Measurements
	OG0001 OG0010

Gamma Glutamyl Transferase (U/L): >3xULN

Title	Measurements
	OG0001 OG0012

Potassium: >5.4 mmol/L

Title	Measurements
	OG0002 OG0014

Sodium: >150 mmol/L

Title	Measurements
	OG0001 OG0011

Hematocrit: Male <0.385 L/L, Female <0.345 L/L

Title	Measurements
	OG0005 OG0013

Hematocrit: Male >0.55 L/L, Female >0.49 L/L

Title	Measurements
	OG0001 OG0010

Hemoglobin: Male <115 g/L, Female <100 g/L

Title	Measurements
	OG0001 OG0011

Neutrophils: <1.5 10^9/L

Title	Measurements
	OG0003 OG0010

Title

Denominators

Categories

Change From Baseline at Day 18

- ParticipantsOG00037
- ParticipantsOG00139

Title	Measurements
	OG000-1.2± 4.70 OG001-1.0± 5.18

Change From Baseline at Day 22

- ParticipantsOG00038
- ParticipantsOG00141

Title	Measurements
	OG000-0.9± 5.08 OG001

Change From Baseline at Day 28

- ParticipantsOG00039
- ParticipantsOG00139

Title	Measurements
	OG000-1.2± 5.56 OG001

Change From Baseline at Day 35

- ParticipantsOG00039
- ParticipantsOG00137

Title	Measurements
	OG000-0.6± 6.47 OG001

Change From Baseline at Day 42

- ParticipantsOG00039
- ParticipantsOG00137

Title	Measurements
	OG000-1.6± 6.58 OG001

ID	Term
D003865	Depressive Disorder, Major
D007319	Sleep Initiation and Maintenance Disorders

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders
D009422	Nervous System Diseases