Trial Outcomes & Findings for A Study to Evaluate the Long-term Safety and Tolerability of SAGE-324 in Participants With Essential Tremor (NCT NCT05366751)

Last Updated: 2025-08-01

Results Overview

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as an AE with onset after the first dose of IP, or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

97 participants

Primary outcome timeframe

Up to 814 days

Results posted on

2025-08-01

Participant Flow

Participants were enrolled at 29 investigative sites in the United States from 03 June 2022 to 10 September 2024.

This was a single-arm study and all participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 milligrams (mg) from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data were collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.

Participant milestones

Participant milestones
Measure	SAGE-324 Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Overall Study STARTED	97
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	97

Reasons for withdrawal

Reasons for withdrawal
Measure	SAGE-324 Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Overall Study Adverse Event	25
Overall Study Physician Decision	3
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	14
Overall Study Study Terminated by Sponsor	50
Overall Study Site Terminated by Sponsor	3

Baseline Characteristics

A Study to Evaluate the Long-term Safety and Tolerability of SAGE-324 in Participants With Essential Tremor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SAGE-324 n=97 Participants Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Age, Continuous	67.3 years STANDARD_DEVIATION 10.48 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	91 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	90 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 814 days

Population: The Safety Set included all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.

Outcome measures

Outcome measures
Measure	SAGE-324 n=97 Participants Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs)	86 Participants

SECONDARY outcome

Timeframe: Up to 814 days

Number of participants with PCS postbaseline vital sign values are summarized for categories: supine and standing (1 and 3 minutes \[min\]) heart rate - maximum absolute value greater than (\>)120 beats/min, minimum absolute value less than (\<)40 beats/min. Supine and standing (1 and 3 min) SBP - maximum absolute value \>180 millimeters of mercury (mmHg), minimum absolute value \<90 mmHg, and increase or decrease from baseline of greater than or equal to (≥)30 mmHg; supine and standing (1 and 3 min) DBP - maximum absolute value \>110 mmHg, minimum absolute value \<50 mmHg, and increase or decrease from baseline of ≥20 mmHg. Only those categories where at least 1 participant met the PCS criterion at least once during postbaseline duration are reported.

Outcome measures

Outcome measures
Measure	SAGE-324 n=97 Participants Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) Heart Rate, Supine, >120 beats/min	1 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) Heart Rate, Standing 1 min, >120 beats/min	2 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) Heart Rate, Standing 3 min, <40 beats/min	1 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) Heart Rate, Standing 3 min, >120 beats/min	1 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) SBP, Supine, Change From Baseline (CFB) ≥30 mmHg	7 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) SBP, Supine, CFB less than or equal to (≤ -30) mmHg	6 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) SBP, Standing 1 min, <90 mmHg	5 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) SBP, Standing 1 min, CFB ≥30 mmHg	6 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) SBP, Standing 1 min, CFB ≤ -30 mmHg	7 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) SBP, Standing 3 min, <90 mmHg	3 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) SBP, Standing 3 min, CFB ≥30 mmHg	8 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) SBP, Standing 3 min, CFB ≤ -30 mmHg	4 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) DBP, Supine, <50 mmHg	2 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) DBP, Supine, CFB ≥20 mmHg	8 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) DBP, Supine, CFB ≤ -20 mmHg	7 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) DBP, Standing 1 min, <50 mmHg	3 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) DBP, Standing 1 min, CFB ≥20 mmHg	6 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) DBP, Standing 1 min, CFB ≤ -20 mmHg	7 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) DBP, Standing 3 min, <50 mmHg	2 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) DBP, Standing 3 min, CFB ≥20 mmHg	6 Participants
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) DBP, Standing 3 min, CFB ≤ -20 mmHg	6 Participants

SECONDARY outcome

Timeframe: Up to 814 days

Number of participants with PCS postbaseline values for QTcF are categorized as follows: absolute value \>450 milliseconds (msec) and ≤480msec; absolute value \>480 msec and ≤500msec; absolute value \>500 msec and increase from baseline \>30 and ≤60 msec; increase from baseline \>60 msec. Only those categories where at least 1 participant met the PCS criterion at least once during postbaseline are reported.

Outcome measures

Outcome measures
Measure	SAGE-324 n=97 Participants Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) >450 msec and ≤480 msec	9 Participants
Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) >480 msec and ≤500 msec	3 Participants
Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) >500 msec	1 Participants
Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) CFB >30 msec and ≤60 msec	11 Participants
Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) CFB >60 msec	2 Participants

SECONDARY outcome

Timeframe: Up to 814 days

Clinical laboratory test values are considered PCS if they meet either the lower-limit or higher-limit PCS criteria defined in the categories below. Number of participants with PCS laboratory values are summarized for clinical chemistry, liver function tests, hematology, and coagulation. Only those categories where at least 1 participant had a non-PCS value at Baseline and met the PCS criterion at least once during post-baseline are reported. Number analyzed is the number of participants with data available for analyses for the specified category.

Outcome measures

Outcome measures
Measure	SAGE-324 n=97 Participants Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Number of Participants With PCS Laboratory Parameters Platelets, Low: <125 10^9/L	2 Participants
Number of Participants With PCS Laboratory Parameters Bicarbonate, Low: <18 millimoles per liter (mmol/L)	1 Participants
Number of Participants With PCS Laboratory Parameters Calcium, High: >2.75 mmol/L	1 Participants
Number of Participants With PCS Laboratory Parameters Glucose, Low: <2.8 mmol/L	1 Participants
Number of Participants With PCS Laboratory Parameters Glucose, High: >13.9 mmol/L	5 Participants
Number of Participants With PCS Laboratory Parameters Phosphate, Low: <0.61 mmol/L	1 Participants
Number of Participants With PCS Laboratory Parameters Potassium, High: >5.4 mmol/L	1 Participants
Number of Participants With PCS Laboratory Parameters Urea Nitrogen, High: >10.71 mmol/L	11 Participants
Number of Participants With PCS Laboratory Parameters Alkaline Phosphatase, >1.5x Upper Limit of Normal (ULN)	1 Participants
Number of Participants With PCS Laboratory Parameters Total Bilirubin, >1.5xULN	2 Participants
Number of Participants With PCS Laboratory Parameters Total Bilirubin, >2xULN	1 Participants
Number of Participants With PCS Laboratory Parameters Hematocrit, Low: <0.385 volume/volume (v/v) (Males)	11 Participants
Number of Participants With PCS Laboratory Parameters Hematocrit, High: >0.55 v/v (Males)	2 Participants
Number of Participants With PCS Laboratory Parameters Hematocrit, Low: <0.345 v/v (Females)	2 Participants
Number of Participants With PCS Laboratory Parameters Hemoglobin, Low: <115 grams/liter (g/L) (Males)	2 Participants
Number of Participants With PCS Laboratory Parameters Lymphocytes, Low: <0.5 10^9 cells per liter (10^9/L)	2 Participants
Number of Participants With PCS Laboratory Parameters Neutrophils, Low: <1.5 10^9/L	2 Participants
Number of Participants With PCS Laboratory Parameters Activated Partial Thromboplastin Time (aPTT) (seconds), >1.5*ULN	5 Participants
Number of Participants With PCS Laboratory Parameters Prothrombin Time (PT) (seconds), ≥1.11 x ULN	18 Participants

SECONDARY outcome

Timeframe: Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 70, 84, 112, 140, 168, 274, 365, 456, 548, 639, 730, 765, End of Treatment [EOT] (anytime, up to Day 793), End of Study [EOS] (anytime, up to Day 814)

Population: The Safety Set included all participants who were administered at least one dose of SAGE-324. Number analyzed is the number of participants with data available for analysis at specified timepoints.

ESS consists of 8 items where participants rate, on a 4-point scale of 0 (no chance of dozing) to 3 (high chance of dozing), their usual chances of dozing off or falling asleep while engaged in 8 different activities. ESS total score is sum of the 8 individual item scores and estimates a participant's average sleep propensity. ESS score can range from 0 to 24. ESS score ≥ 10 was used to indicate excessive daytime sleepiness. A higher score indicates more severe excessive daytime sleepiness. Baseline was defined as last non-missing measurement prior to the first dose of investigational product. All participants received SAGE-324 according to a predefined up-titration scheme. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.

Outcome measures

Outcome measures
Measure	SAGE-324 n=97 Participants Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 548	-1.3 score on a scale Standard Deviation 1.80
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 43	0.9 score on a scale Standard Deviation 3.39
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 50	1.0 score on a scale Standard Deviation 4.23
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 57	0.7 score on a scale Standard Deviation 3.55
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 70	0.7 score on a scale Standard Deviation 3.35
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 84	0.8 score on a scale Standard Deviation 3.31
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 112	0.3 score on a scale Standard Deviation 2.42
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 140	0.0 score on a scale Standard Deviation 2.40
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 168	0.3 score on a scale Standard Deviation 2.79
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 274	0.4 score on a scale Standard Deviation 3.11
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 365	-0.5 score on a scale Standard Deviation 3.23
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 456	-0.1 score on a scale Standard Deviation 2.82
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 639	-1.5 score on a scale Standard Deviation 3.21
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 730	1.7 score on a scale Standard Deviation 1.53
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 765	-1.3 score on a scale Standard Deviation 2.52
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at EOT (anytime, up to Day 793)	1.3 score on a scale Standard Deviation 3.39
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at EOS (anytime, up to Day 814)	-0.2 score on a scale Standard Deviation 2.90
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Baseline	5.0 score on a scale Standard Deviation 3.25
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 8	-0.4 score on a scale Standard Deviation 1.55
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 15	0.0 score on a scale Standard Deviation 2.66
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 22	0.2 score on a scale Standard Deviation 2.95
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 29	0.3 score on a scale Standard Deviation 3.08
Change From Baseline in Epworth Sleepiness Scale (ESS) Score Change From Baseline at Day 36	1.0 score on a scale Standard Deviation 3.89

SECONDARY outcome

Timeframe: Baseline up to Day 814

Population: The Safety Set. Number analyzed are number of participants with data available at specified timepoint. All participants received SAGE-324 according to a predefined up-titration scheme. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.

C-SSRS scale consists of baseline evaluation that assesses lifetime experience of participant with suicidal ideation \& behavior, \& post-baseline evaluation that focuses on suicidality since last study visit. C-SSRS included 'yes'/'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1-5, with 5 being most severe). Higher score indicated more severe symptoms. If any of assessments in suicidal behavior are 'Yes', category is considered as 'Suicidal behavior'. If any of assessments in suicidal ideation is 'Yes', but all assessments in suicidal behavior are 'No', category is considered as 'Suicidal ideation'. Baseline: any 'Yes' in any question in suicidal ideation/behavior prior to first dose of investigational product, excluding lifetime assessments. Data is reported for only those timepoints where participants had at least one 'yes' response to suicidal ideation or suicidal behavior except at Baseline.

Outcome measures

Outcome measures
Measure	SAGE-324 n=97 Participants Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Baseline · No Suicidal Ideation/Behavior	97 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Baseline · Suicidal Ideation	0 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Baseline · Suicidal Behavior	0 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Day 70 · No Suicidal Ideation/Behavior	74 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Day 70 · Suicidal Ideation	1 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Day 70 · Suicidal Behavior	1 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Day 84 · No Suicidal Ideation/Behavior	69 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Day 84 · Suicidal Ideation	1 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Day 84 · Suicidal Behavior	0 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Day 112 · No Suicidal Ideation/Behavior	63 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Day 112 · Suicidal Ideation	2 Participants
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Day 112 · Suicidal Behavior	0 Participants

SECONDARY outcome

Timeframe: EOT (anytime, up to Day 793), EOS (anytime, up to Day 814)

Population: The Safety Set included all participants who were administered at least one dose of SAGE-324. Number analyzed are unique number of participants out of all the assessed participants with data available at the specified timepoint. Different participants may have contributed data for each timepoint.

PWC is based on 35-item Penn Physician Withdrawal Checklist that was developed to measure benzodiazepine and benzodiazepine-like discontinuation symptoms. PWC-20 is a shorter version of Penn Physician Withdrawal Checklist and is made up of a list of 20 symptoms (e.g., loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability) that are rated on a scale of 0 (not present) to 3 (severe). Total scores can range from 0 to 60; higher scores indicating more severe symptoms. PWC-20 assessments were conducted at EOT and EOS to monitor for presence of potential withdrawal symptoms following discontinuation of IP. EOT was defined as first available assessment after last dose of study treatment and within 1 day of last dose of study treatment. All participants received SAGE-324 according to a predefined up-titration scheme. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.

Outcome measures

Outcome measures
Measure	SAGE-324 n=97 Participants Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Physician Withdrawal Checklist (PWC-20) Scale Total Score EOT (anytime, up to Day 793)	6.5 score on a scale Standard Deviation 7.33
Physician Withdrawal Checklist (PWC-20) Scale Total Score EOS (anytime, up to Day 814)	5.0 score on a scale Standard Deviation 6.14

Adverse Events

SAGE-324

Serious events: 6 serious events

Other events: 86 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SAGE-324 n=97 participants at risk Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Nervous system disorders Aphasia	1.0% 1/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Infections and infestations COVID-19	1.0% 1/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Vascular disorders Deep vein thrombosis	1.0% 1/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Nervous system disorders Hypoaesthesia	1.0% 1/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Psychiatric disorders Mental status changes	1.0% 1/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Injury, poisoning and procedural complications Multiple injuries	1.0% 1/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Musculoskeletal and connective tissue disorders Muscular weakness	1.0% 1/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Injury, poisoning and procedural complications Post procedural haemorrhage	1.0% 1/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.0% 1/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Injury, poisoning and procedural complications Road traffic accident	1.0% 1/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.

Other adverse events

Other adverse events
Measure	SAGE-324 n=97 participants at risk Participants received SAGE-324 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43, orally, once daily.
Nervous system disorders Somnolence	50.5% 49/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Nervous system disorders Dizziness	15.5% 15/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Nervous system disorders Balance disorder	8.2% 8/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Nervous system disorders Cognitive disorder	6.2% 6/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Nervous system disorders Tremor	6.2% 6/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Infections and infestations COVID-19	10.3% 10/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Infections and infestations Urinary tract infection	8.2% 8/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Infections and infestations Upper respiratory tract infection	5.2% 5/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Psychiatric disorders Depression	7.2% 7/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Psychiatric disorders Insomnia	6.2% 6/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Psychiatric disorders Abnormal dreams	5.2% 5/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
General disorders Fatigue	11.3% 11/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
General disorders Feeling abnormal	7.2% 7/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Injury, poisoning and procedural complications Fall	7.2% 7/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
Gastrointestinal disorders Diarrhea	6.2% 6/97 • Up to 814 days The Safety Set: all participants who were administered at least one dose of SAGE-324. All participants received SAGE-324 according to a predefined up-titration scheme as follows: 15 mg from Day 1 to Day 14, followed by up-titration to 30 mg from Day 15 to Day 28, then to 45 mg from Day 29 to Day 42, and then 60 mg starting on Day 43. Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.

Additional Information

Carrie Vaudreuil

Sage Therapeutics

Phone: +1-857-259-4766

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI can either be a party and subject to the same restrictions as the institution, or if not a party, the restrictions are described on the face of the contract (i.e., PI is a contractor of the institution; PI is part of a larger group of study personnel; institution has contracted with or otherwise bound all study personnel under confidentiality obligations and requirements to vest intellectual property to the institution).
Publication restrictions are in place

Restriction type: OTHER