A Phase 2/3 interventional study of SAGE-324 in Essential Tremor, sponsored by Sage Therapeutics. Terminated at 38 sites in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2025-08-01.
Sponsored by Sage Therapeutics · Phase 2/3, Interventional, and Treatment
The primary purpose of this study is to evaluate the long-term safety and tolerability of SAGE-324 in participants with essential tremor (ET).
261 studies on the registry are indexed under Essential Tremor; 74 are open to participants now.
This study's enrollment of 97 is above the median of 24 across 185 interventional studies indexed under Essential Tremor.
Browse Essential Tremor studies →Sage Therapeutics is the lead sponsor of 6 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Participant has a clinician-confirmed diagnosis of ET in compliance with all the following criteria:
Participant is willing to limit use of alcohol to 2 units per day for males and 1 unit per day for females starting at least 1 week prior to Day 1 and through the End of Study (EOS) Visit.
Exclusion Criteria:
Participants will receive SAGE-324 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, orally, once daily.
Drug: SAGE-324
SAGE-324 oral tablets
Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs)
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.
Time frame: Up to 814 days
Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP)
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.
Time frame: Up to 814 days
Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF])
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.
Time frame: Up to 814 days
Number of Participants With PCS Laboratory Parameters
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.
Time frame: Up to 814 days
Change From Baseline in Epworth Sleepiness Scale (ESS) Score
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.
Time frame: 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)
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses
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.
Time frame: Baseline up to Day 814
Physician Withdrawal Checklist (PWC-20) Scale Total Score
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.
Time frame: EOT (anytime, up to Day 793), EOS (anytime, up to Day 814)
Participants were enrolled at 29 investigative sites in the United States from 03 June 2022 to 10 September 2024.
| Milestone | SAGE-324 |
|---|---|
| Started | 97 |
| Completed | 0 |
| Not completed | 97 |
| Withdrew: Adverse event | 25 |
| Withdrew: Physician decision | 3 |
| Withdrew: Lost to follow-up | 2 |
| Withdrew: Withdrawal by subject | 14 |
| Withdrew: Study terminated by sponsor | 50 |
| Withdrew: Site terminated by sponsor | 3 |
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.
| Participants | SAGE-324 |
|---|---|
| Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) | 86 |
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.
| Participants | SAGE-324 |
|---|---|
| Heart Rate, Supine, >120 beats/min | 1 |
| Heart Rate, Standing 1 min, >120 beats/min | 2 |
| Heart Rate, Standing 3 min, <40 beats/min | 1 |
| Heart Rate, Standing 3 min, >120 beats/min | 1 |
| SBP, Supine, Change From Baseline (CFB) ≥30 mmHg | 7 |
| SBP, Supine, CFB less than or equal to (≤ -30) mmHg | 6 |
| SBP, Standing 1 min, <90 mmHg | 5 |
| SBP, Standing 1 min, CFB ≥30 mmHg | 6 |
| SBP, Standing 1 min, CFB ≤ -30 mmHg | 7 |
| SBP, Standing 3 min, <90 mmHg | 3 |
| SBP, Standing 3 min, CFB ≥30 mmHg | 8 |
| SBP, Standing 3 min, CFB ≤ -30 mmHg | 4 |
| DBP, Supine, <50 mmHg | 2 |
| DBP, Supine, CFB ≥20 mmHg | 8 |
| DBP, Supine, CFB ≤ -20 mmHg | 7 |
| DBP, Standing 1 min, <50 mmHg | 3 |
| DBP, Standing 1 min, CFB ≥20 mmHg | 6 |
| DBP, Standing 1 min, CFB ≤ -20 mmHg | 7 |
| DBP, Standing 3 min, <50 mmHg | 2 |
| DBP, Standing 3 min, CFB ≥20 mmHg | 6 |
| DBP, Standing 3 min, CFB ≤ -20 mmHg | 6 |
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.
| Participants | SAGE-324 |
|---|---|
| >450 msec and ≤480 msec | 9 |
| >480 msec and ≤500 msec | 3 |
| >500 msec | 1 |
| CFB >30 msec and ≤60 msec | 11 |
| CFB >60 msec | 2 |
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.
| Participants | SAGE-324 |
|---|---|
| Bicarbonate, Low: <18 millimoles per liter (mmol/L) | 1 |
| Calcium, High: >2.75 mmol/L | 1 |
| Glucose, Low: <2.8 mmol/L | 1 |
| Glucose, High: >13.9 mmol/L | 5 |
| Phosphate, Low: <0.61 mmol/L | 1 |
| Potassium, High: >5.4 mmol/L | 1 |
| Urea Nitrogen, High: >10.71 mmol/L | 11 |
| Alkaline Phosphatase, >1.5x Upper Limit of Normal (ULN) | 1 |
| Total Bilirubin, >1.5xULN | 2 |
| Total Bilirubin, >2xULN | 1 |
| Hematocrit, Low: <0.385 volume/volume (v/v) (Males) | 11 |
| Hematocrit, High: >0.55 v/v (Males) | 2 |
| Hematocrit, Low: <0.345 v/v (Females) | 2 |
| Hemoglobin, Low: <115 grams/liter (g/L) (Males) | 2 |
| Lymphocytes, Low: <0.5 10^9 cells per liter (10^9/L) | 2 |
| Neutrophils, Low: <1.5 10^9/L | 2 |
| Platelets, Low: <125 10^9/L | 2 |
| Activated Partial Thromboplastin Time (aPTT) (seconds), >1.5*ULN | 5 |
| Prothrombin Time (PT) (seconds), ≥1.11 x ULN | 18 |
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.
| score on a scale | SAGE-324 |
|---|---|
| Baseline | 5.0 ± 3.25 |
| Change From Baseline at Day 8 | -0.4 ± 1.55 |
| Change From Baseline at Day 15 | 0.0 ± 2.66 |
| Change From Baseline at Day 22 | 0.2 ± 2.95 |
| Change From Baseline at Day 29 | 0.3 ± 3.08 |
| Change From Baseline at Day 36 | 1.0 ± 3.89 |
| Change From Baseline at Day 43 | 0.9 ± 3.39 |
| Change From Baseline at Day 50 | 1.0 ± 4.23 |
| Change From Baseline at Day 57 | 0.7 ± 3.55 |
| Change From Baseline at Day 70 | 0.7 ± 3.35 |
| Change From Baseline at Day 84 | 0.8 ± 3.31 |
| Change From Baseline at Day 112 | 0.3 ± 2.42 |
| Change From Baseline at Day 140 | 0.0 ± 2.40 |
| Change From Baseline at Day 168 | 0.3 ± 2.79 |
| Change From Baseline at Day 274 | 0.4 ± 3.11 |
| Change From Baseline at Day 365 | -0.5 ± 3.23 |
| Change From Baseline at Day 456 | -0.1 ± 2.82 |
| Change From Baseline at Day 548 | -1.3 ± 1.80 |
| Change From Baseline at Day 639 | -1.5 ± 3.21 |
| Change From Baseline at Day 730 | 1.7 ± 1.53 |
| Change From Baseline at Day 765 | -1.3 ± 2.52 |
| Change From Baseline at EOT (anytime, up to Day 793) | 1.3 ± 3.39 |
| Change From Baseline at EOS (anytime, up to Day 814) | -0.2 ± 2.90 |
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.
| Participants | SAGE-324 |
|---|---|
| Baseline — No Suicidal Ideation/Behavior | 97 |
| Baseline — Suicidal Ideation | 0 |
| Baseline — Suicidal Behavior | 0 |
| Day 70 — No Suicidal Ideation/Behavior | 74 |
| Day 70 — Suicidal Ideation | 1 |
| Day 70 — Suicidal Behavior | 1 |
| Day 84 — No Suicidal Ideation/Behavior | 69 |
| Day 84 — Suicidal Ideation | 1 |
| Day 84 — Suicidal Behavior | 0 |
| Day 112 — No Suicidal Ideation/Behavior | 63 |
| Day 112 — Suicidal Ideation | 2 |
| Day 112 — Suicidal Behavior | 0 |
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.
| score on a scale | SAGE-324 |
|---|---|
| EOT (anytime, up to Day 793) | 6.5 ± 7.33 |
| EOS (anytime, up to Day 814) | 5.0 ± 6.14 |
Collected over Up to 814 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| SAGE-324 | 0/97 (0%) | 6/97 (6.2%) | 86/97 (88.7%) |
| Event | SAGE-324 |
|---|---|
| AphasiaNervous system disorders | 1/97 |
| COVID-19Infections and infestations | 1/97 |
| Deep vein thrombosisVascular disorders | 1/97 |
| HypoaesthesiaNervous system disorders | 1/97 |
| Mental status changesPsychiatric disorders | 1/97 |
| Multiple injuriesInjury, poisoning and procedural complications | 1/97 |
| Muscular weaknessMusculoskeletal and connective tissue disorders | 1/97 |
| Post procedural haemorrhageInjury, poisoning and procedural complications | 1/97 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 1/97 |
| Road traffic accidentInjury, poisoning and procedural complications | 1/97 |
| Event | SAGE-324 |
|---|---|
| SomnolenceNervous system disorders | 49/97 |
| DizzinessNervous system disorders | 15/97 |
| FatigueGeneral disorders | 11/97 |
| COVID-19Infections and infestations | 10/97 |
| Balance disorderNervous system disorders | 8/97 |
| Urinary tract infectionInfections and infestations | 8/97 |
| DepressionPsychiatric disorders | 7/97 |
| Feeling abnormalGeneral disorders | 7/97 |
| FallInjury, poisoning and procedural complications | 7/97 |
| Cognitive disorderNervous system disorders | 6/97 |
The Safety Set included all participants who were administered at least one dose of SAGE-324.
| Age, Continuous(years) | SAGE-324 |
|---|---|
| Mean | 67.3 ± 10.48 |
| Sex: Female, Male(Participants) | SAGE-324 |
|---|---|
| Female | 31 |
| Male | 66 |
| Ethnicity (NIH/OMB)(Participants) | SAGE-324 |
|---|---|
| Hispanic or Latino | 5 |
| Not Hispanic or Latino | 91 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | SAGE-324 |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 5 |
| White | 90 |
| More than one race | 1 |
| Unknown or Not Reported | 0 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No — Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
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