Essential Tremor
Conditions
Keywords
Essential Tremor, SAGE-324
Brief summary
This is a phase 2, double-blind, placebo-controlled study to evaluate the safety and efficacy of SAGE-324 compared to placebo on upper limb (UL) tremor reduction in individuals with essential tremor (ET).
Interventions
DRUGSAGE-324
SAGE-324 oral tablet
DRUGSAGE-324 Placebo
SAGE-324 matched placebo oral tablet
Sponsors
Sage Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participant has a diagnosis of ET, defined as isolated tremor syndrome consisting of bilateral upper limb action tremor for at least 3 years prior to screening, with or without tremor in other locations and absence of other neurological signs, such as dystonia, ataxia, or parkinsonism, isolated focal tremors (e.g., voice, head), task- and position-specific tremors, sudden tremor onset or evidence of step-wise deterioration of tremor. * Participant scores at least 1.5 for each of the six items that comprise the combined total upper limb the essential tremor rating assessment scale (TETRAS) (total performance subscale part 4) with the total score for the dominant upper limb (the sum of the three items for either the right or left upper limb, whichever is dominant) being at least 5.5, at both Screening and pre-dose on Day 1. * Participant is willing to discontinue medications taken for the treatment of ET within 14 days or 5 half-lives prior to receiving investigational product (IP). Medications taken for the treatment of ET that were discontinued prior to receiving IP may be resumed following Day 29. * Participant has no clinically significant findings, as determined by the investigator, on Screening and pre-dose Day 1 physical examination including mental state examination (MSE) and neurologic examination, 12-lead electrocardiogram (ECG), or screening clinical laboratory tests.
Exclusion criteria
* Participant has a presence of known causes of enhanced physiological tremor. * Participant has had recent exposure (14 days prior to Day 1) to tremorgenic drugs. * Participant has had direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor. * Participant has had a previous procedure for the treatment of ET, deep brain stimulation, brain lesioning, or magnetic resonance (MR)-guided procedure, e.g., MR-guided focused ultrasound. * Participant has historical or clinical evidence of tremor with psychogenic origin (including but not limited to eating disorders, major depression, etc.). * Participant has history of suicidal behavior within 2 years or answers YES to questions 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or at Day 1 or is currently at risk for suicide in the opinion of the investigator. * Participant has used any known moderate or strong cytochrome P450 3A4 and/or inducers within 14 days or 5 half-lives (whichever is longer) prior to Day 1 or consumed grapefruit juice, grapefruit, Seville oranges, pomegranates, tangelos, or St. John's Wort or products containing these within 30 days prior to Day 1. Use of mild cytochrome inhibitors and/or inducers may be permitted. * Participant has concurrent or recent exposure (14 days or 5 half-lives, whichever is longer, prior to the Day 1 visit) to sedative/hypnotic drugs, stimulants, highly-caffeinated beverages or dietary supplements containing high doses of caffeine, or recent increase above regular daily consumption of caffeine. * Participant currently uses or has used within 14 days or 5 half-lives (whichever is longer) prior to Day 1, any prescription or over-the-counter medication that is a substrate of the organic anion transporting polypeptide 1B1 (OATP1B1) transporter.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score on Day 29 | Baseline, Day 29 | The Essential Tremor Rating Assessment Scale (TETRAS) is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. The TETRAS performance subscale upper limb tremor total score is the sum of the TETRAS individual item scores from both arms of the body. The TETRAS individual item score included TETRAS Performance Subscale items 4a, 4b, and 4c scores \[4a: limbs extended forward maneuver, 4b: wing-beating (elbows flexed) maneuver, and 4c: kinetic (finger-nose-finger) maneuver\] scores from both arms of the body. Each individual item score ranges from 0 to 4; with 0 to 12 being the score range for each arm of the body. The total upper limb score combined for both arms ranges from 0 to 24. Higher scores=more severe tremor. A negative change from baseline =improvement. Mixed model repeated measures (MMRM) was used for the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, and 42 | TETRAS is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. The TETRAS performance subscale upper limb tremor total score is the sum of the TETRAS individual item scores from both arms of the body. The TETRAS individual item score included TETRAS Performance Subscale items 4a, 4b, and 4c scores \[4a: limbs extended forward maneuver, 4b: wing-beating (elbows flexed) maneuver, and 4c: kinetic (finger-nose-finger) maneuver\] scores from both arms of the body. Each individual item score ranges from 0 to 4; with 0 to 12 being the score range for each arm of the body. The total upper limb score combined for both arms ranges from 0 to 24. Higher scores=more severe tremor. A negative change from baseline =improvement. MMRM was used for the analysis. |
| Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42 | Kinesia ONE™ measures three-dimensional motion converted to scores. Motion in both arms were captured. The accelerometer-based Kinesia ONE individual scores is the sum of the individual item scores across both arms of the body. The individual items included forward outstretched postural tremor, lateral wing beating postural tremor, and kinetic tremor scores from both arms of the body. Each individual item score ranges from 0 (no tremor) to 4 (severe tremor); with 0 to 12 being the score range for each arm of the body. The Kinesia ONE total score combined for both arms ranges from 0 to 24. Higher scores=more tremors/greater tremor amplitude. A negative change from baseline indicates improvement. MMRM was used for the analysis. |
| Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Baseline, Days 8, 15, 22, 29, and 42 | The ADL subscale assesses how ET impacts typical activities of daily living (speech, eating, drinking, dressing, personal hygiene, writing, occupational impairment, social impact, and activities affected by UL tremor. It consists of 12 items, each rated from 0 (normal activity) to 4 (severe abnormality). The overall ADL score, calculated as the sum of subscale items ranges from 0 to 48. Higher scores indicate greater tremor severity, while a negative change from baseline indicates improvement. MMRM was used for the analysis. |
| Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42 | The total performance score is based on the overall rating of tremor amplitude in the voice, limbs, head, face, and trunk while performing pre-specified tasks, and functional task capabilities (handwriting, spiral drawing, and holding a pen over a dot). Each of these items is rated from 0 (no tremor) to 4 (severe tremor) with an overall performance score of 0 to 64, calculated as the sum of subscale items. Higher scores indicate greater tremor severity. A negative change from baseline indicates improvement. MMRM was used for the analysis. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From the first dose of the study drug up to the end of the study (i.e., up to approximately 42 days) | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with the treatment. A TEAE was defined as an AE with onset after the start of investigational product (IP), or any worsening of a preexisting medical condition/AE with onset after the start of IP and throughout the study. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 27 active investigative sites in the United States from 19 May 2020 to 15 February 2021.
Pre-assignment details
A total of 153 participants were screened, of which 69 participants were randomized to receive SAGE-324 or placebo.
Participants by arm
| Arm | Count |
|---|---|
| SAGE-324 60 mg Participants received SAGE-324, 60 mg, oral tablets, QD, in the morning for 28 days. | 34 |
| SAGE-324 Matched Placebo Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days. | 35 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Participant | 8 | 1 |
Baseline characteristics
| Characteristic | SAGE-324 60 mg | SAGE-324 Matched Placebo | Total |
|---|---|---|---|
| Age, Continuous | 69.4 years STANDARD_DEVIATION 6.91 | 64.7 years STANDARD_DEVIATION 13.18 | 67.0 years STANDARD_DEVIATION 10.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 29 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Kinesia ONE™ Accelerometer Score | 10.66 score on a scale STANDARD_DEVIATION 3.825 | 8.80 score on a scale STANDARD_DEVIATION 3.762 | 9.73 score on a scale STANDARD_DEVIATION 3.879 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 32 Participants | 64 Participants |
| Region of Enrollment United States | 34 participants | 35 participants | 69 participants |
| Sex: Female, Male Female | 12 Participants | 20 Participants | 32 Participants |
| Sex: Female, Male Male | 22 Participants | 15 Participants | 37 Participants |
| TETRAS Activities of Daily Living (ADL) Score | 26.33 score on a scale STANDARD_DEVIATION 8.502 | 26.74 score on a scale STANDARD_DEVIATION 6.837 | 26.54 score on a scale STANDARD_DEVIATION 7.646 |
| TETRAS Total Performance Subscale Score | 27.68 score on a scale STANDARD_DEVIATION 4.618 | 27.09 score on a scale STANDARD_DEVIATION 5.157 | 27.38 score on a scale STANDARD_DEVIATION 4.871 |
| Tremor Rating Assessment Scale (TETRAS) Performance Subscale Item 4 Upper Limb Tremor Score | 12.82 score on a scale STANDARD_DEVIATION 1.727 | 12.28 score on a scale STANDARD_DEVIATION 1.698 | 12.54 score on a scale STANDARD_DEVIATION 1.72 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 35 |
| other Total, other adverse events | 29 / 34 | 15 / 35 |
| serious Total, serious adverse events | 3 / 34 | 1 / 35 |
Outcome results
Primary
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score on Day 29
The Essential Tremor Rating Assessment Scale (TETRAS) is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. The TETRAS performance subscale upper limb tremor total score is the sum of the TETRAS individual item scores from both arms of the body. The TETRAS individual item score included TETRAS Performance Subscale items 4a, 4b, and 4c scores \[4a: limbs extended forward maneuver, 4b: wing-beating (elbows flexed) maneuver, and 4c: kinetic (finger-nose-finger) maneuver\] scores from both arms of the body. Each individual item score ranges from 0 to 4; with 0 to 12 being the score range for each arm of the body. The total upper limb score combined for both arms ranges from 0 to 24. Higher scores=more severe tremor. A negative change from baseline =improvement. Mixed model repeated measures (MMRM) was used for the analysis.
Time frame: Baseline, Day 29
Population: Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score on Day 29 | -2.31 score on a scale | Standard Error 0.401 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score on Day 29 | -1.24 score on a scale | Standard Error 0.349 |
p-value: 0.049195% CI: [-2.14, 0]MMRM
Secondary
Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42
Kinesia ONE™ measures three-dimensional motion converted to scores. Motion in both arms were captured. The accelerometer-based Kinesia ONE individual scores is the sum of the individual item scores across both arms of the body. The individual items included forward outstretched postural tremor, lateral wing beating postural tremor, and kinetic tremor scores from both arms of the body. Each individual item score ranges from 0 (no tremor) to 4 (severe tremor); with 0 to 12 being the score range for each arm of the body. The Kinesia ONE total score combined for both arms ranges from 0 to 24. Higher scores=more tremors/greater tremor amplitude. A negative change from baseline indicates improvement. MMRM was used for the analysis.
Time frame: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42
Population: Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 42 | -0.78 score on a scale | Standard Error 0.557 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, 8 Hours Post-dose | -0.85 score on a scale | Standard Error 0.585 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 22 | -0.50 score on a scale | Standard Error 0.54 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 29 | -0.48 score on a scale | Standard Error 0.562 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 8 | -1.00 score on a scale | Standard Error 0.47 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, Pre-dose | -0.44 score on a scale | Standard Error 0.499 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, 5 Hours Post-dose | -1.94 score on a scale | Standard Error 0.613 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, 5 Hours Post-dose | -1.45 score on a scale | Standard Error 0.551 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 8 | -0.90 score on a scale | Standard Error 0.451 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, 8 Hours Post-dose | -1.39 score on a scale | Standard Error 0.532 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 22 | -0.83 score on a scale | Standard Error 0.491 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, Pre-dose | -1.37 score on a scale | Standard Error 0.462 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 29 | -1.12 score on a scale | Standard Error 0.497 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 42 | -1.44 score on a scale | Standard Error 0.534 |
Comparison: Change From Baseline at Day 8p-value: 0.878495% CI: [-1.42, 1.21]MMRM
Comparison: Change From Baseline at Day 15, Pre-dosep-value: 0.179595% CI: [-0.44, 2.3]MMRM
Comparison: Change From Baseline at Day 15, 5 Hours Post-dosep-value: 0.558895% CI: [-2.15, 1.17]MMRM
Comparison: Change From Baseline at Day 15, 8 Hours Post-dosep-value: 0.503695% CI: [-1.06, 2.13]MMRM
Comparison: Change From Baseline at Day 22p-value: 0.663695% CI: [-1.15, 1.79]MMRM
Comparison: Change From Baseline at Day 29p-value: 0.399995% CI: [-0.87, 2.15]MMRM
Comparison: Change From Baseline at Day 42p-value: 0.393395% CI: [-0.88, 2.22]MMRM
Secondary
Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42
The ADL subscale assesses how ET impacts typical activities of daily living (speech, eating, drinking, dressing, personal hygiene, writing, occupational impairment, social impact, and activities affected by UL tremor. It consists of 12 items, each rated from 0 (normal activity) to 4 (severe abnormality). The overall ADL score, calculated as the sum of subscale items ranges from 0 to 48. Higher scores indicate greater tremor severity, while a negative change from baseline indicates improvement. MMRM was used for the analysis.
Time frame: Baseline, Days 8, 15, 22, 29, and 42
Population: Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15 | -5.43 score on a scale | Standard Error 0.945 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 29 | -4.24 score on a scale | Standard Error 0.94 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 22 | -5.24 score on a scale | Standard Error 0.904 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 42 | -2.14 score on a scale | Standard Error 0.905 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 8 | -5.34 score on a scale | Standard Error 0.845 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 42 | -3.27 score on a scale | Standard Error 0.837 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 8 | -2.54 score on a scale | Standard Error 0.805 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15 | -2.47 score on a scale | Standard Error 0.859 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 22 | -2.68 score on a scale | Standard Error 0.802 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 29 | -2.87 score on a scale | Standard Error 0.78 |
Comparison: Change From Baseline at Day 8p-value: 0.019395% CI: [-5.14, -0.47]MMRM
Comparison: Change From Baseline at Day 15p-value: 0.024395% CI: [-5.51, -0.4]MMRM
Comparison: Change From Baseline at Day 22p-value: 0.038595% CI: [-4.98, -0.14]MMRM
Comparison: Change From Baseline at Day 29p-value: 0.268295% CI: [-3.81, 1.08]MMRM
Comparison: Change From Baseline at Day 42p-value: 0.364995% CI: [-1.34, 3.59]MMRM
Secondary
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42
TETRAS is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. The TETRAS performance subscale upper limb tremor total score is the sum of the TETRAS individual item scores from both arms of the body. The TETRAS individual item score included TETRAS Performance Subscale items 4a, 4b, and 4c scores \[4a: limbs extended forward maneuver, 4b: wing-beating (elbows flexed) maneuver, and 4c: kinetic (finger-nose-finger) maneuver\] scores from both arms of the body. Each individual item score ranges from 0 to 4; with 0 to 12 being the score range for each arm of the body. The total upper limb score combined for both arms ranges from 0 to 24. Higher scores=more severe tremor. A negative change from baseline =improvement. MMRM was used for the analysis.
Time frame: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, and 42
Population: Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 42 | -1.23 score on a scale | Standard Error 0.407 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 8 | -1.67 score on a scale | Standard Error 0.287 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 15, Pre-dose | -1.78 score on a scale | Standard Error 0.344 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 15, 5 Hours Post-dose | -2.64 score on a scale | Standard Error 0.452 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 15, 8 Hours Post-dose | -2.36 score on a scale | Standard Error 0.441 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 22 | -2.10 score on a scale | Standard Error 0.36 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 15, 8 Hours Post-dose | -2.09 score on a scale | Standard Error 0.389 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 42 | -1.85 score on a scale | Standard Error 0.378 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 15, 5 Hours Post-dose | -2.24 score on a scale | Standard Error 0.4 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 8 | -0.86 score on a scale | Standard Error 0.273 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 22 | -1.33 score on a scale | Standard Error 0.318 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 | Change From Baseline at Day 15, Pre-dose | -1.31 score on a scale | Standard Error 0.312 |
Comparison: Change From Baseline at Day 8p-value: 0.046895% CI: [-1.6, -0.01]MMRM
Comparison: Change From Baseline at Day 15, Pre-dosep-value: 0.312495% CI: [-1.41, 0.46]MMRM
Comparison: Change From Baseline at Day 15, 5 Hours Post-dosep-value: 0.514895% CI: [-1.61, 0.81]MMRM
Comparison: Change From Baseline at Day 15, 8 Hours Post-dosep-value: 0.645295% CI: [-1.45, 0.91]MMRM
Comparison: Change From Baseline at Day 22p-value: 0.117195% CI: [-1.73, 0.2]MMRM
Comparison: Change From Baseline at Day 42p-value: 0.272495% CI: [-0.5, 1.73]MMRM
Secondary
Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42
The total performance score is based on the overall rating of tremor amplitude in the voice, limbs, head, face, and trunk while performing pre-specified tasks, and functional task capabilities (handwriting, spiral drawing, and holding a pen over a dot). Each of these items is rated from 0 (no tremor) to 4 (severe tremor) with an overall performance score of 0 to 64, calculated as the sum of subscale items. Higher scores indicate greater tremor severity. A negative change from baseline indicates improvement. MMRM was used for the analysis.
Time frame: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42
Population: Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, Pre-dose | -3.46 score on a scale | Standard Error 0.878 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 22 | -3.16 score on a scale | Standard Error 0.914 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 8 | -3.55 score on a scale | Standard Error 0.78 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 29 | -3.22 score on a scale | Standard Error 0.922 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, 5 Hours Post-dose | -5.90 score on a scale | Standard Error 1.015 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 42 | -1.59 score on a scale | Standard Error 0.82 |
| SAGE-324 60 mg | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, 8 Hours Post-dose | -4.61 score on a scale | Standard Error 0.954 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 42 | -3.87 score on a scale | Standard Error 0.761 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 8 | -2.30 score on a scale | Standard Error 0.743 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, Pre-dose | -2.55 score on a scale | Standard Error 0.805 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, 8 Hours Post-dose | -4.61 score on a scale | Standard Error 0.855 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 22 | -2.92 score on a scale | Standard Error 0.811 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 29 | -2.90 score on a scale | Standard Error 0.817 |
| SAGE-324 Matched Placebo | Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 | Change From Baseline at Day 15, 5 Hours Post-dose | -4.38 score on a scale | Standard Error 0.892 |
Comparison: Change From Baseline at Day 8p-value: 0.247895% CI: [-3.41, 0.9]MMRM
Comparison: Change From Baseline at Day 15, Pre-dosep-value: 0.448695% CI: [-3.29, 1.47]MMRM
Comparison: Change From Baseline at Day 15, 5 Hours Post-dosep-value: 0.266295% CI: [-4.22, 1.19]MMRM
Comparison: Change From Baseline at Day 15, 8 Hours Post-dosep-value: 0.996595% CI: [-2.56, 2.57]MMRM
Comparison: Change From Baseline at Day 22p-value: 0.843795% CI: [-2.68, 2.2]MMRM
Comparison: Change From Baseline at Day 29p-value: 0.79695% CI: [-2.78, 2.14]MMRM
Comparison: Change From Baseline at Day 42p-value: 0.045695% CI: [0.05, 4.52]MMRM
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with the treatment. A TEAE was defined as an AE with onset after the start of investigational product (IP), or any worsening of a preexisting medical condition/AE with onset after the start of IP and throughout the study.
Time frame: From the first dose of the study drug up to the end of the study (i.e., up to approximately 42 days)
Population: Safety Set included all participants who were administered SAGE-324 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAGE-324 60 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 33 Participants |
| SAGE-324 Matched Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 20 Participants |