Essential Tremor
Conditions
Keywords
SAGE-324
Brief summary
The primary purpose of this study is to evaluate the long-term safety and tolerability of SAGE-324 in participants with essential tremor (ET).
Interventions
DRUGSAGE-324
SAGE-324 oral tablets
Sponsors
Sage Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Participant is in good physical health and has no clinically significant findings (excluding ET) that may impact their ability to participate in the study, as determined by the investigator, on physical examination, 12-lead electrocardiogram (ECG), or clinical laboratory tests. 2. Participant has a clinician-confirmed diagnosis of ET in compliance with all the following criteria: 1. Duration of at least 3 years 2. Absence of other neurological signs, such as dystonia, ataxia, parkinsonism, task- and position-specific tremors, sudden tremor onset, or evidence of stepwise deterioration of tremor 3. Absence of historical or clinical evidence of tremor with psychogenic origin (including, but not limited to, eating disorders and major depression) 3. Participant has completed the planned end of treatment (EOT) visit and was not early terminated during the planned Treatment Period in another SAGE-324 study. 4. 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. 1. Participant will limit alcohol use to at least 2 hours before self-administration of investigational product (IP) in the evening. 2. Participant will not use alcohol starting 24 hours prior to scheduled in-clinic study visits until all assessments have been completed. 5. Participant is willing to maintain prestudy consumption of products that contain nicotine starting at least 1 week prior to Day 1 and through EOS Visit.
Exclusion criteria
1. Participant has presence of alcohol withdrawal state. 2. Participant has had direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor. 3. Participant is taking and unable to discontinue the use of primidone at least 7 days prior to administration of the first dose of SAGE-324. 4. Participant has a history (within 3 years of Screening) or ongoing oncologic disease, excluding skin cancers (squamous or basal cell carcinoma) for which treatment has been completed and any carcinoma in situ. 5. Participant has an ongoing clinically relevant medical or psychiatric condition that, in the judgment of the investigator, is not well managed and poses a risk for participation in the study. 6. Participant has history of substance dependence and/or abuse prior to Screening, has a positive screen for drugs of abuse at Screening or predose on Day 1. Participants with nicotine use disorder that impacts their tremor are excluded. 7. Participant has a known allergy to SAGE-324 or any excipient. 8. Female participant has a positive pregnancy test or confirmed pregnancy or is breastfeeding. 9. Participant has had exposure to another investigational drug or device within 30 days or 5 half-lives of the other investigational drug, whichever is longer, prior to the Day 1 visit and for the duration of the study. 10. Participant has a history of suicidal behavior within 2 years or answers YES to questions 3, 4, or 5 on the C-SSRS at Screening or at Day 1 or is currently at risk of suicide in the opinion of the investigator. 11. Participant has any condition or comorbidity that in the opinion of the investigator would limit or interfere with the participant's ability to complete or partake in the study. 12. Participant has used any known moderate or strong cytochrome P450 3A4 inhibitors and/or inducers within 14 days or 5 half-lives (whichever is longer) prior to Day 1 or consumed grapefruit juice, grapefruit, Seville oranges, or St. John's Wort or products containing these within 30 days prior to Day 1 and is unwilling to refrain from taking these medications or foods for the duration of dosing. Use of mild cytochrome inhibitors and/or inducers may be permitted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) | 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 medical condition/AE with onset after the start of IP and throughout the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) | 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. |
| Number of Participants With PCS Laboratory Parameters | 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. |
| Number of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements: Heart Rate, Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) | 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. |
| Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | 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 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. |
| Physician Withdrawal Checklist (PWC-20) Scale Total Score | 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 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. |
| Change From Baseline in Epworth Sleepiness Scale (ESS) Score | 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. 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. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 29 investigative sites in the United States from 03 June 2022 to 10 September 2024.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 97 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 25 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Site Terminated by Sponsor | 3 |
| Overall Study | Study Terminated by Sponsor | 50 |
| Overall Study | Withdrawal by Subject | 14 |
Baseline characteristics
| Characteristic | SAGE-324 |
|---|---|
| Age, Continuous | 67.3 years STANDARD_DEVIATION 10.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 90 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 97 |
| other Total, other adverse events | 86 / 97 |
| serious Total, serious adverse events | 6 / 97 |
Outcome results
Primary
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
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAGE-324 | Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) | 86 Participants |
Secondary
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)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-324 | Change From Baseline in Epworth Sleepiness Scale (ESS) Score | Baseline | 5.0 score on a scale | Standard Deviation 3.25 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | Change From Baseline in Epworth Sleepiness Scale (ESS) Score | Change From Baseline at Day 140 | 0.0 score on a scale | Standard Deviation 2.4 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | Change From Baseline in Epworth Sleepiness Scale (ESS) Score | Change From Baseline at Day 548 | -1.3 score on a scale | Standard Deviation 1.8 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 2.9 |
Secondary
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
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.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Baseline | No Suicidal Ideation/Behavior | 97 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Baseline | Suicidal Ideation | 0 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Baseline | Suicidal Behavior | 0 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Day 70 | No Suicidal Ideation/Behavior | 74 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Day 70 | Suicidal Ideation | 1 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Day 70 | Suicidal Behavior | 1 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Day 84 | No Suicidal Ideation/Behavior | 69 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Day 84 | Suicidal Ideation | 1 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Day 84 | Suicidal Behavior | 0 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Day 112 | No Suicidal Ideation/Behavior | 63 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Day 112 | Suicidal Ideation | 2 Participants |
| SAGE-324 | Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Responses | Day 112 | Suicidal Behavior | 0 Participants |
Secondary
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
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAGE-324 | Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) | >450 msec and ≤480 msec | 9 Participants |
| SAGE-324 | Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) | >480 msec and ≤500 msec | 3 Participants |
| SAGE-324 | Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) | >500 msec | 1 Participants |
| SAGE-324 | 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 |
| SAGE-324 | Number of Participants With PCS Electrocardiogram (ECG) Findings for QT Corrected According to Fridericia's Formula [QTcF]) | CFB >60 msec | 2 Participants |
Secondary
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
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Glucose, Low: <2.8 mmol/L | 1 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Bicarbonate, Low: <18 millimoles per liter (mmol/L) | 1 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Calcium, High: >2.75 mmol/L | 1 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Glucose, High: >13.9 mmol/L | 5 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Phosphate, Low: <0.61 mmol/L | 1 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Potassium, High: >5.4 mmol/L | 1 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Urea Nitrogen, High: >10.71 mmol/L | 11 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Alkaline Phosphatase, >1.5x Upper Limit of Normal (ULN) | 1 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Total Bilirubin, >1.5xULN | 2 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Total Bilirubin, >2xULN | 1 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Hematocrit, Low: <0.385 volume/volume (v/v) (Males) | 11 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Hematocrit, High: >0.55 v/v (Males) | 2 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Hematocrit, Low: <0.345 v/v (Females) | 2 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Hemoglobin, Low: <115 grams/liter (g/L) (Males) | 2 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Lymphocytes, Low: <0.5 10^9 cells per liter (10^9/L) | 2 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Neutrophils, Low: <1.5 10^9/L | 2 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Platelets, Low: <125 10^9/L | 2 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Activated Partial Thromboplastin Time (aPTT) (seconds), >1.5*ULN | 5 Participants |
| SAGE-324 | Number of Participants With PCS Laboratory Parameters | Prothrombin Time (PT) (seconds), ≥1.11 x ULN | 18 Participants |
Secondary
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
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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 |
| SAGE-324 | 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
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)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-324 | Physician Withdrawal Checklist (PWC-20) Scale Total Score | EOT (anytime, up to Day 793) | 6.5 score on a scale | Standard Deviation 7.33 |
| SAGE-324 | Physician Withdrawal Checklist (PWC-20) Scale Total Score | EOS (anytime, up to Day 814) | 5.0 score on a scale | Standard Deviation 6.14 |