NCT05366751

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

Terminated Phase 2, PHASE3 Results posted Last updated 1 August 2025

What this trial tests

Phase 2, PHASE3 trial testing SAGE-324 in Essential Tremor in 97 participants. Terminated before completion.

Timeline

3 June 2022

Primary endpoint
10 September 2024

10 September 2024

Quick facts

Lead sponsor	Sage Therapeutics
Phase	Phase 2, PHASE3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	97
Start date	3 June 2022
Primary completion	10 September 2024
Estimated completion	10 September 2024
Sites	38 locations across United States

Drugs / interventions tested

• SAGE-324 — full drug profile →

Conditions studied

• Essential Tremor — all drugs for Essential Tremor →

Sponsor

Sage Therapeutics — full company profile →

Who can join

Adults 18 to 80, any sex, with Essential Tremor. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) Primary · Up to 814 days

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 medica

Group	Value	95% CI
SAGE-324	86

Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) Secondary · 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 dec

Heart Rate, Supine, >120 beats/min

Group	Value	95% CI
SAGE-324	1

Heart Rate, Standing 1 min, >120 beats/min

Group	Value	95% CI
SAGE-324	2

Heart Rate, Standing 3 min, <40 beats/min

Group	Value	95% CI
SAGE-324	1

Heart Rate, Standing 3 min, >120 beats/min

Group	Value	95% CI
SAGE-324	1

SBP, Supine, Change From Baseline (CFB) ≥30 mmHg

Group	Value	95% CI
SAGE-324	7

SBP, Supine, CFB less than or equal to (≤ -30) mmHg

Group	Value	95% CI
SAGE-324	6

SBP, Standing 1 min, <90 mmHg

Group	Value	95% CI
SAGE-324	5

SBP, Standing 1 min, CFB ≥30 mmHg

Group	Value	95% CI
SAGE-324	6

Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) Secondary · 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.

>450 msec and ≤480 msec

Group	Value	95% CI
SAGE-324	9

>480 msec and ≤500 msec

Group	Value	95% CI
SAGE-324	3

>500 msec

Group	Value	95% CI
SAGE-324	1

CFB >30 msec and ≤60 msec

Group	Value	95% CI
SAGE-324	11

CFB >60 msec

Group	Value	95% CI
SAGE-324	2

Number of Participants With PCS Laboratory Parameters Secondary · 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.

Bicarbonate, Low: <18 millimoles per liter (mmol/L)

Group	Value	95% CI
SAGE-324	1

Calcium, High: >2.75 mmol/L

Group	Value	95% CI
SAGE-324	1

Glucose, Low: <2.8 mmol/L

Group	Value	95% CI
SAGE-324	1

Glucose, High: >13.9 mmol/L

Group	Value	95% CI
SAGE-324	5

Phosphate, Low: <0.61 mmol/L

Group	Value	95% CI
SAGE-324	1

Potassium, High: >5.4 mmol/L

Group	Value	95% CI
SAGE-324	1

Urea Nitrogen, High: >10.71 mmol/L

Group	Value	95% CI
SAGE-324	11

Alkaline Phosphatase, >1.5x Upper Limit of Normal (ULN)

Group	Value	95% CI
SAGE-324	1

Change From Baseline in Epworth Sleepiness Scale (ESS) Score Secondary · 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)

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.

Baseline

Group	Value	95% CI
SAGE-324	5.0	± 3.25

Change From Baseline at Day 8

Group	Value	95% CI
SAGE-324	-0.4	± 1.55

Change From Baseline at Day 15

Group	Value	95% CI
SAGE-324	0.0	± 2.66

Change From Baseline at Day 22

Group	Value	95% CI
SAGE-324	0.2	± 2.95

Change From Baseline at Day 29

Group	Value	95% CI
SAGE-324	0.3	± 3.08

Change From Baseline at Day 36

Group	Value	95% CI
SAGE-324	1.0	± 3.89

Change From Baseline at Day 43

Group	Value	95% CI
SAGE-324	0.9	± 3.39

Change From Baseline at Day 50

Group	Value	95% CI
SAGE-324	1.0	± 4.23

Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses Secondary · Baseline up to Day 814

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

Baseline

Group	Value	95% CI
SAGE-324	97
SAGE-324	0
SAGE-324	0

Day 70

Group	Value	95% CI
SAGE-324	74
SAGE-324	1
SAGE-324	1

Day 84

Group	Value	95% CI
SAGE-324	69
SAGE-324	1
SAGE-324	0

Day 112

Group	Value	95% CI
SAGE-324	63
SAGE-324	2
SAGE-324	0

Physician Withdrawal Checklist (PWC-20) Scale Total Score Secondary · EOT (anytime, up to Day 793), EOS (anytime, up to Day 814)

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 f

EOT (anytime, up to Day 793)

Group	Value	95% CI
SAGE-324	6.5	± 7.33

EOS (anytime, up to Day 814)

Group	Value	95% CI
SAGE-324	5.0	± 6.14

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 814 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

SAGE-324

Serious: 6/97 (6%)

Deaths: 0/97

Serious adverse events (10 terms)

Reaction	System	SAGE-324
Aphasia	Nervous system disorders	—
COVID-19	Infections and infestations	—
Deep vein thrombosis	Vascular disorders	—
Hypoaesthesia	Nervous system disorders	—
Mental status changes	Psychiatric disorders	—
Multiple injuries	Injury, poisoning and procedural complications	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—
Post procedural haemorrhage	Injury, poisoning and procedural complications	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—
Road traffic accident	Injury, poisoning and procedural complications	—

Other adverse events (15 terms — click to expand)

Reaction	System	SAGE-324
Somnolence	Nervous system disorders	—
Dizziness	Nervous system disorders	—
Fatigue	General disorders	—
COVID-19	Infections and infestations	—
Balance disorder	Nervous system disorders	—
Urinary tract infection	Infections and infestations	—
Depression	Psychiatric disorders	—
Feeling abnormal	General disorders	—
Fall	Injury, poisoning and procedural complications	—
Cognitive disorder	Nervous system disorders	—
Tremor	Nervous system disorders	—
Insomnia	Psychiatric disorders	—
Diarrhea	Gastrointestinal disorders	—
Upper respiratory tract infection	Infections and infestations	—
Abnormal dreams	Psychiatric disorders	—

Most-reported serious reactions: Aphasia, COVID-19, Deep vein thrombosis, Hypoaesthesia, Mental status changes, Multiple injuries, Muscular weakness, Post procedural haemorrhage.

Data from ClinicalTrials.gov NCT05366751 adverse events section.

Sponsor's own description

The primary purpose of this study is to evaluate the long-term safety and tolerability of SAGE-324 in participants with essential tremor (ET).

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Supportive care of female hormones in brain health: what and how?
   Zhu A, Song S, Pei L, Huang Y. · · 2024 · cited 2× · PMID 39114348 · DOI 10.3389/fphar.2024.1403969