Essential Tremor
Conditions
Keywords
Tremor
Brief summary
This study is a three-part, multicenter, Phase 2a study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of SAGE-217 in adult participants with essential tremor.
Detailed description
Part A of the study was an open-label design with morning dosing of SAGE-217 for 7 days and included 16 participants, 8 of whom qualified for, and entered, Part B. Part B had a double-blind, placebo-controlled, randomized withdrawal design with morning dosing for 7 days. Part C was an open-label design with morning and evening dosing for 14 days and included a different set of 18 participants. Parts A and B were stopped early (in advance of the planned sample size). This study was previously posted by Sage Therapeutics. In November 2023, sponsorship of the trial was transferred to Biogen.
Interventions
DRUGSAGE-217
SAGE-217 Oral Solution
DRUGPlacebo
SAGE-217 matching placebo capsules
Sponsors
Biogen
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
Key Inclusion Criteria: * Participant must have a diagnosis of Essential Tremor (ET), defined as bilateral postural tremor and kinetic tremor, involving hands and forearms, that is visible and persistent and the duration is \>5 years prior to screening. Key
Exclusion criteria
* Participant has presence of abnormal neurological signs other than tremor or Froment's sign. * Participant has presence of known causes of enhanced physiological tremor. * Participant has concurrent or recent exposure (14 days prior to admission visit) to tremorogenic drugs. * Participant has had direct or indirect trauma to the nervous system within 3 months before the onset of tremor. * Participant has historical or clinical evidence of tremor with psychogenic origin. * Participant has convincing evidence of sudden tremor onset or evidence of stepwise deterioration of tremor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7 | Baseline (Day 1) and Day 7 (8 hours postdose) | The accelerometer-based Kinesia kinetic tremor combined score is the sum of Kinesia kinetic tremor scores across both sides of the body. Tremor is measured using a motion sensor that transmits raw data to a computer where it converts the tremor amplitude to a Kinesia score of 0 to 4 based on validated algorithms; the total score ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Baseline indicates improvement. |
| Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14 | Randomization (Day 8, predose) and Day 14 (predose) | The accelerometer-based Kinesia kinetic tremor combined score is the sum of Kinesia kinetic tremor scores across both sides of the body. Tremor is measured using a motion sensor that transmits raw data to a computer where it converts the tremor amplitude to a Kinesia score of 0 to 4 based on validated algorithms; the total score ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement. |
| Part C: Change From Baseline in the Accelerometer-based Kinesia Upper Limb Tremor Combined Score at Day 15 | Baseline (Day 1) and Day 15 | The accelerometer-based Kinesia upper limb total score is the sum of the individual item scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 | Baseline (Day 1) and Day 7 (8 hours postdose) | The TETRAS individual item score is the sum of the TETRAS Performance Subscale items 4a, 4b, or 4c scores \[4a: forward outstretched postural tremor (FOPT), 4b: lateral wing beating postural tremor (LWBPT), 4c: kinetic tremor\] from both sides of the body. Each TETRAS score ranges from 0 to 4; the total score ranges from 0 to 16; higher scores indicate more severe tremor. A negative change from Baseline indicates improvement. |
| Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 | Baseline (Day 1) and Day 7 (predose) | The TETRAS Performance Subscale score includes 9 items. Out of these 9 items, Item 6 is Archimedes spirals (AS), Item 7 is Handwriting, and Item 8 is Dot approximation task (DAT). Each item was scored from 0 to 4, for both sides of the body, each item has a total score of 0 to 8, where higher scores indicate more severe tremor. A negative change from Baseline indicates improvement. |
| Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14 | Randomization (Day 8, predose) and Day 14 (predose) | The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Randomization indicates improvement. |
| Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 | Randomization (Day 8, predose) and Day 14 (predose) | The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Randomization indicates improvement. |
| Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14 | Randomization (Day 8, predose) and Day 14 (predose) | The TETRAS performance subscale upper limb total score is the sum of the TETRAS individual item scores from both sides of the body. The TETRAS individual item score included TETRAS Performance Subscale item 4a, 4b and 4c scores \[4a: forward outstretched postural tremor (FOPT) and 4b: lateral wing beating postural tremor (LWBPT) scores and 4c: Kinetic tremor (KT) score\] from both sides of the body. Each individual item score ranges from 0 to 4; The total upper limb score ranges from 0 to 24, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement. |
| Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 | Randomization (Day 8, predose) and Day 14 (predose) | The TETRAS individual item score is the sum of the TETRAS Performance Subscale item 4a and 4b scores \[4a: forward outstretched postural tremor (FOPT) and 4b: lateral wing beating postural tremor (LWBPT) scores\] from both sides of the body. Each TETRAS score ranges from 0 to 4; the total score ranges from 0 to 16, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement. |
| Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14 | Randomization (Day 8, predose) and Day 14 (predose) | The TETRAS kinetic tremor combined score is the sum of the TETRAS Performance Subscale item 4c (kinetic tremor) scores from both sides of the body. The TETRAS kinetic tremor score ranges from 0 to 4, the total score for both sides of the body ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement. |
| Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | Baseline (Day 1) and Day 14 (predose) | The TETRAS Performance Subscale score includes 9 items. Out of these 9 items, Item 6 is Archimedes spirals (AS), Item 7 is Handwriting, and Item 8 is Dot approximation task (DAT). Each item was scored from 0 to 4, for both sides of the body, each item has a total score of 0 to 8, where higher scores indicate more severe tremor. A negative change from Baseline indicates improvement. |
| Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 | Baseline (Day 1) and Day 15 | The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement. |
| Part C: Change From Baseline in the TETRAS Upper Limb Total Score at Day 15 | Baseline (Day 1) and Day 15 | The TETRAS performance subscale upper limb total score is the sum of the TETRAS individual item scores from both sides of the body. Each individual item score ranges from 0 to 4; The total upper limb score ranges from 0 to 24, higher scores indicate more severe tremor. A negative change indicates improvement. |
| Part A: Change From Baseline in Kinesia Upper Limb Total Score at Day 7 | Baseline (Day 1) and Day 7 (8 hours postdose) | The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement. |
| Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 | Baseline (Day 1) and Day 15 | The TETRAS Performance Subscale score includes 9 items. Out of these 9 items, Item 6 is Archimedes spirals (AS), Item 7 is Handwriting, and Item 8 is Dot approximation task (DAT). Each item was scored from 0 to 4, for both sides of the body, each item has a total score of 0 to 8, where higher scores indicate more severe tremor. A negative change from Baseline indicates improvement. |
| Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | From first dose of study drug through 14 days after the last dose (Up to 28 days) | An Adverse Event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. Adverse events that occurred after the first administration of study drug were denoted as TEAEs. A Serious Adverse Event (SAE) was an AE occurring during any study phase and at any dose of the study drug, comparator, or placebo, that fulfilled the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. |
| Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Baseline and post-baseline (up to 28 days) | The C-SSRS consists of a baseline and post-baseline (PB) evaluation that assesses the lifetime experience of the participants with suicidal ideation and behavior. The data for suicidal ideation were summarized for participants who answered 'Yes'. Suicide ideation was categorized as 1) wish to be dead and 2) non-specific active suicidal thoughts. |
| Number of Participants With Clinically Significant Vital Signs | Up to 28 days | Vital signs included heart rate, respiratory rate, temperature, and blood pressure. |
| Number of Participants With Clinically Significant Laboratory Parameters | Up to 28 days | Laboratory parameters included hematology, blood chemistry, and urinalysis. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Values | Up to 28 days | A 12-lead ECG was performed. |
| Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS) | Baseline (Day 1), Day 7 (predose) for Part A, Day 14 (predose) for Part B | The SSS was designed to quickly assess how alert a subject is feeling. Degrees of sleepiness and alertness are rated on a scale of 1 to 7, where the lowest score of 1 indicates the subject is feeling active, vital, alert, or wide awake and the highest score of 7 indicates the participant is no longer fighting sleep, sleep onset soon; having dream-like thoughts. Greater changes from baseline indicate greater sedation. A positive change from baseline indicates improvement. |
| Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Baseline (Day 1), Day 7 (predose) for Part A, Day 14 (predose) for Part B and Day 15 for Part C | Mood was assessed using the Bond-Lader VAS score. This is a 16-part self-administered questionnaire that employs a 100-mm VAS to explore different aspects of self-reported mood. Three factor scores for (alertness, contentedness, and calmness) were calculated using following equations based on normalized VAS scores: * Alertness = 0.827X1 + 0.618X3 + 0.755X4 + 0.642X5 + 0.776X6 + 0.635X9 + 0.792X11 + 0.593X12 + 0.614X15; * Contentedness = 0.677X7 + 0.697X8 + 0.823X13 + 0.738X14 + 0.594X16; and * Calmness = 0.845X2 + 0.677X10, where Xi represents a subject's item score after normalization, and i represents the item number from the entire scale (in order from 1-16). A negative change from baseline (CFB) indicated more alertness, more contentedness, and more calmness. |
| Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Baseline (Day 1), Day 7 (2 hours postdose) for Part A, Day 14 (2 hours postdose) for Part B and Day 15 for Part C | Participants responded to 5 DEQs based on how they are feeling after taking the study drug. DEQ-5 were as follows; Q1: Do you FEEL a drug effect right now? Q2: Are you HIGH right now? Q3: Do you DISLIKE any of the effects that you are feeling right now? Q4: Do you LIKE any of the effects that you are feeling right now? Q5: Would you like MORE of the drug you took, right now? The answers were recorded on a 100-mm VAS, with the answer for each being Not at all (0 mm) and Extremely (100 mm) at the extremes. There were options to record Not applicable for questions 3 and 4 if no drug effects were felt and for question 5 prior to administration of study medication, and these participants were excluded from the data summarization. Higher score on Q1 indicates a drug effect; on Q2 indicates feeling high; on Q3 indicates disliking the drug; and on Q4 and Q5 indicates liking the drug. |
| Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 | Baseline (Day 1) and Day 15 | The TETRAS individual item score is the sum of the TETRAS Performance Subscale item 4a and 4b scores \[4a: forward outstretched postural tremor (FOPT) and 4b: lateral wing beating postural tremor (LWBPT) scores\] from both sides of the body. Each TETRAS score ranges from 0 to 4; the total score ranges from 0 to 16, higher scores indicate more severe tremor. A negative change from Baseline indicates improvement. |
| Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 | Baseline (Day 1) and Day 7 (8 hours [hr] postdose [pd]) | The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4, with higher scores indicating more tremors/greater tremor amplitude. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement. |
| Part A: Change From Baseline in the Tremor Research Group (TRG) Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Total Score at Day 7 | Baseline (Day 1) and Day 7 (8 hours postdose) | The TETRAS performance subscale upper limb total score is the sum of the TETRAS individual item scores from both sides of the body. The TETRAS individual item score included TETRAS Performance Subscale item 4a, 4b and 4c scores \[4a: forward outstretched postural tremor (FOPT) and 4b: lateral wing beating postural tremor (LWBPT) scores and 4c: Kinetic tremor (KT) score\] from both sides of the body. Each individual item score ranges from 0 to 4; The total upper limb score ranges from 0 to 24, higher scores indicate more severe tremor. A negative change indicates improvement. |
Countries
United States
Participant flow
Recruitment details
A total of 34 participants were enrolled in the study from 11 investigation sites in United States.
Pre-assignment details
A total of 34 participants enrolled in the study. 16 participants received either SAGE-217 oral solution (N=2) or capsules (N=14) in Part A; 8 participants who tolerated a dose ≥10 mg in Part A and achieved response on Day 8 were randomized (1:1) in Part B to Placebo or SAGE-217 capsules.18 participants received SAGE-217 capsules in Part C.
Participants by arm
| Arm | Count |
|---|---|
| Part A: SAGE-217 Oral Solution Participants received SAGE-217 10 mg on Day 1, 20 mg on Day 2 and 30 mg daily on Days 3 to 7 as an oral solution with food in the morning. | 2 |
| Part A: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217, capsules administered with food in the morning on Day 1, 20 mg with food on Day 2 and 30 mg with food daily on Days 3 to 7. | 14 |
| Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening. | 18 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Part A | Adverse Event | 1 | 1 | 0 | 0 | 0 |
| Part A | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
| Part B | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
| Part C | Adverse Event | 0 | 0 | 0 | 0 | 2 |
| Part C | Tremor not improved due to Topamax discontinuation | 0 | 0 | 0 | 0 | 1 |
| Part C | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A: SAGE-217 Oral Solution | Part A: SAGE-217 Capsules | Part C: SAGE-217 Capsules | Total |
|---|---|---|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 0.71 | 62.4 years STANDARD_DEVIATION 8.34 | 65.8 years STANDARD_DEVIATION 8.21 | 64.7 years STANDARD_DEVIATION 8.24 |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 2 Participants | 14 Participants | 18 Participants | 34 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 11 Participants | 18 Participants | 30 Participants |
| Region of Enrollment United States | 2 participants | 14 participants | 18 participants | 34 participants |
| Sex: Female, Male Female | 1 Participants | 7 Participants | 10 Participants | 18 Participants |
| Sex: Female, Male Male | 1 Participants | 7 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 14 | 0 / 4 | 0 / 4 | 0 / 18 |
| other Total, other adverse events | 2 / 2 | 7 / 14 | 0 / 4 | 1 / 4 | 10 / 18 |
| serious Total, serious adverse events | 1 / 2 | 0 / 14 | 0 / 4 | 0 / 4 | 0 / 18 |
Outcome results
Primary
Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7
The accelerometer-based Kinesia kinetic tremor combined score is the sum of Kinesia kinetic tremor scores across both sides of the body. Tremor is measured using a motion sensor that transmits raw data to a computer where it converts the tremor amplitude to a Kinesia score of 0 to 4 based on validated algorithms; the total score ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) and Day 7 (8 hours postdose)
Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7 | Baseline (Day 1) | 4.36 score on a scale | Standard Deviation 1.199 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7 | Change from Baseline at Day 7 (8 hours postdose) | -0.69 score on a scale | Standard Deviation 1.115 |
Primary
Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14
The accelerometer-based Kinesia kinetic tremor combined score is the sum of Kinesia kinetic tremor scores across both sides of the body. Tremor is measured using a motion sensor that transmits raw data to a computer where it converts the tremor amplitude to a Kinesia score of 0 to 4 based on validated algorithms; the total score ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement.
Time frame: Randomization (Day 8, predose) and Day 14 (predose)
Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14 | Randomization (Day 8) | 3.33 score on a scale | Standard Deviation 0.714 |
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14 | Change from Randomization at Day 14 (predose) | 0.20 score on a scale | Standard Deviation 0.271 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14 | Randomization (Day 8) | 4.13 score on a scale | Standard Deviation 1.438 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14 | Change from Randomization at Day 14 (predose) | 0.15 score on a scale | Standard Deviation 0.191 |
Comparison: Change from Randomization at Day 14 (predose)p-value: 0.914395% CI: [-0.44, 0.49]Mixed Model for Repeated Measures (MMRM)
Primary
Part C: Change From Baseline in the Accelerometer-based Kinesia Upper Limb Tremor Combined Score at Day 15
The accelerometer-based Kinesia upper limb total score is the sum of the individual item scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) and Day 15
Population: The Efficacy Population consisted of all participants who completed at least 1 dose of study drug in Part C and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the Accelerometer-based Kinesia Upper Limb Tremor Combined Score at Day 15 | Baseline (Day 1) | 11.68 score on a scale | Standard Deviation 3.822 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the Accelerometer-based Kinesia Upper Limb Tremor Combined Score at Day 15 | Change from Baseline at Day 15 | -2.22 score on a scale | Standard Deviation 2.956 |
Comparison: Change from Baseline at Day 15p-value: 0.052995% CI: [-3.5, 0.03]Mixed Model for Repeated Measures (MMRM)
Secondary
Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7
The TETRAS individual item score is the sum of the TETRAS Performance Subscale items 4a, 4b, or 4c scores \[4a: forward outstretched postural tremor (FOPT), 4b: lateral wing beating postural tremor (LWBPT), 4c: kinetic tremor\] from both sides of the body. Each TETRAS score ranges from 0 to 4; the total score ranges from 0 to 16; higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) and Day 7 (8 hours postdose)
Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 | FOPT at Baseline (Day 1) | 4.14 score on a scale | Standard Deviation 0.989 |
| Part A: SAGE-217 Capsules | Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 | Change from Baseline in FOPT at Day 7 | -1.46 score on a scale | Standard Deviation 1.07 |
| Part A: SAGE-217 Capsules | Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 | LWBPT at Baseline (Day 1) | 4.18 score on a scale | Standard Deviation 0.932 |
| Part A: SAGE-217 Capsules | Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 | Change from Baseline in LWBPT at Day 7 | -1.31 score on a scale | Standard Deviation 1.011 |
| Part A: SAGE-217 Capsules | Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 | Kinetic Tremor at Baseline (Day 1) | 4.54 score on a scale | Standard Deviation 0.72 |
| Part A: SAGE-217 Capsules | Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 | Change from Baseline in Kinetic Tremor at Day 7 | -1.65 score on a scale | Standard Deviation 1.179 |
Secondary
Number of Participants With Clinically Significant Electrocardiogram (ECG) Values
A 12-lead ECG was performed.
Time frame: Up to 28 days
Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: SAGE-217 Capsules | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values | 0 Participants |
| Part B: SAGE-217 Capsules | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values | 0 Participants |
| Part B: Placebo | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values | 0 Participants |
| Part B: SAGE-217 Capsules | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values | 0 Participants |
| Part C: SAGE-217 Capsules | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Laboratory Parameters
Laboratory parameters included hematology, blood chemistry, and urinalysis.
Time frame: Up to 28 days
Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: SAGE-217 Capsules | Number of Participants With Clinically Significant Laboratory Parameters | 0 Participants |
| Part B: SAGE-217 Capsules | Number of Participants With Clinically Significant Laboratory Parameters | 0 Participants |
| Part B: Placebo | Number of Participants With Clinically Significant Laboratory Parameters | 0 Participants |
| Part B: SAGE-217 Capsules | Number of Participants With Clinically Significant Laboratory Parameters | 0 Participants |
| Part C: SAGE-217 Capsules | Number of Participants With Clinically Significant Laboratory Parameters | 0 Participants |
Secondary
Number of Participants With Clinically Significant Vital Signs
Vital signs included heart rate, respiratory rate, temperature, and blood pressure.
Time frame: Up to 28 days
Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: SAGE-217 Capsules | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Part B: SAGE-217 Capsules | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Part B: Placebo | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Part B: SAGE-217 Capsules | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Part C: SAGE-217 Capsules | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
Secondary
Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score
The C-SSRS consists of a baseline and post-baseline (PB) evaluation that assesses the lifetime experience of the participants with suicidal ideation and behavior. The data for suicidal ideation were summarized for participants who answered 'Yes'. Suicide ideation was categorized as 1) wish to be dead and 2) non-specific active suicidal thoughts.
Time frame: Baseline and post-baseline (up to 28 days)
Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Wish to be Dead (baseline) | 0 Participants |
| Part A: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Wish to be Dead (PB) | 0 Participants |
| Part A: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Non-Specific Active Suicidal Thoughts (baseline) | 0 Participants |
| Part A: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Non-Specific Active Suicidal Thoughts (PB) | 0 Participants |
| Part B: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Wish to be Dead (baseline) | 0 Participants |
| Part B: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Non-Specific Active Suicidal Thoughts (PB) | 0 Participants |
| Part B: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Wish to be Dead (PB) | 0 Participants |
| Part B: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Non-Specific Active Suicidal Thoughts (baseline) | 0 Participants |
| Part B: Placebo | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Non-Specific Active Suicidal Thoughts (PB) | 0 Participants |
| Part B: Placebo | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Wish to be Dead (PB) | 1 Participants |
| Part B: Placebo | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Non-Specific Active Suicidal Thoughts (baseline) | 0 Participants |
| Part B: Placebo | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Wish to be Dead (baseline) | 1 Participants |
| Part B: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Wish to be Dead (baseline) | 0 Participants |
| Part B: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Wish to be Dead (PB) | 0 Participants |
| Part B: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Non-Specific Active Suicidal Thoughts (PB) | 0 Participants |
| Part B: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Non-Specific Active Suicidal Thoughts (baseline) | 0 Participants |
| Part C: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Non-Specific Active Suicidal Thoughts (PB) | 0 Participants |
| Part C: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Non-Specific Active Suicidal Thoughts (baseline) | 0 Participants |
| Part C: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Wish to be Dead (PB) | 0 Participants |
| Part C: SAGE-217 Capsules | Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Wish to be Dead (baseline) | 0 Participants |
Secondary
Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7
The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4, with higher scores indicating more tremors/greater tremor amplitude. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) and Day 7 (8 hours [hr] postdose [pd])
Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 | FOPT at Baseline (Day 1) | 2.51 score on a scale | Standard Deviation 1.749 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 | Change from Baseline in FOPT at Day 7 (8 hr pd) | -0.74 score on a scale | Standard Deviation 1.339 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 | LWBPT at Baseline (Day 1) | 3.63 score on a scale | Standard Deviation 1.695 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 | Change from Baseline in LWBPT at Day 7 (8 hr pd) | -0.97 score on a scale | Standard Deviation 1.312 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 | Kinetic tremor at Baseline (Day 1) | 4.36 score on a scale | Standard Deviation 1.199 |
Secondary
Part A: Change From Baseline in Kinesia Upper Limb Total Score at Day 7
The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) and Day 7 (8 hours postdose)
Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in Kinesia Upper Limb Total Score at Day 7 | Baseline (Day 1) | 10.50 score on a scale | Standard Deviation 4.395 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in Kinesia Upper Limb Total Score at Day 7 | Change from Baseline at Day 7 (8 hours postdose) | -2.40 score on a scale | Standard Deviation 3.395 |
Secondary
Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7
The TETRAS Performance Subscale score includes 9 items. Out of these 9 items, Item 6 is Archimedes spirals (AS), Item 7 is Handwriting, and Item 8 is Dot approximation task (DAT). Each item was scored from 0 to 4, for both sides of the body, each item has a total score of 0 to 8, where higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) and Day 7 (predose)
Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 | AS at Baseline (Day 1) | 4.8 score on a scale | Standard Deviation 1.37 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 | Change from Baseline in AS at Day 7 | -1.0 score on a scale | Standard Deviation 1.29 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 | Handwriting at Baseline (Day 1) | 2.3 score on a scale | Standard Deviation 1.07 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 | Change from Baseline in Handwriting at Day 7 | -0.4 score on a scale | Standard Deviation 0.77 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 | DAT at Baseline (Day 1) | 4.46 score on a scale | Standard Deviation 0.692 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 | Change from Baseline in DAT at Day 7 | -0.96 score on a scale | Standard Deviation 0.967 |
Secondary
Part A: Change From Baseline in the Tremor Research Group (TRG) Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Total Score at Day 7
The TETRAS performance subscale upper limb total score is the sum of the TETRAS individual item scores from both sides of the body. The TETRAS individual item score included TETRAS Performance Subscale item 4a, 4b and 4c scores \[4a: forward outstretched postural tremor (FOPT) and 4b: lateral wing beating postural tremor (LWBPT) scores and 4c: Kinetic tremor (KT) score\] from both sides of the body. Each individual item score ranges from 0 to 4; The total upper limb score ranges from 0 to 24, higher scores indicate more severe tremor. A negative change indicates improvement.
Time frame: Baseline (Day 1) and Day 7 (8 hours postdose)
Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in the Tremor Research Group (TRG) Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Total Score at Day 7 | Baseline (Day 1) | 12.86 score on a scale | Standard Deviation 2.373 |
| Part A: SAGE-217 Capsules | Part A: Change From Baseline in the Tremor Research Group (TRG) Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Total Score at Day 7 | Change from Baseline at Day 7 | -4.42 score on a scale | Standard Deviation 2.964 |
Secondary
Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14
The TETRAS Performance Subscale score includes 9 items. Out of these 9 items, Item 6 is Archimedes spirals (AS), Item 7 is Handwriting, and Item 8 is Dot approximation task (DAT). Each item was scored from 0 to 4, for both sides of the body, each item has a total score of 0 to 8, where higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) and Day 14 (predose)
Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | AS at Baseline (Day 1) | 5.0 score on a scale | Standard Deviation 0.82 |
| Part A: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | Change from Baseline in AS at Day 14 | -1.3 score on a scale | Standard Deviation 0.96 |
| Part A: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | Handwriting at Baseline (Day 1) | 2.3 score on a scale | Standard Deviation 0.96 |
| Part A: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | Change from Baseline in Handwriting at Day 14 | -0.5 score on a scale | Standard Deviation 1 |
| Part A: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | DAT at Baseline (Day 1) | 4.63 score on a scale | Standard Deviation 0.629 |
| Part A: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | Change from Baseline in DAT at Day 14 | -1.25 score on a scale | Standard Deviation 0.866 |
| Part B: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | DAT at Baseline (Day 1) | 4.50 score on a scale | Standard Deviation 1 |
| Part B: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | AS at Baseline (Day 1) | 5.3 score on a scale | Standard Deviation 1.89 |
| Part B: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | Change from Baseline in Handwriting at Day 14 | -0.5 score on a scale | Standard Deviation 0.58 |
| Part B: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | Change from Baseline in AS at Day 14 | -1.0 score on a scale | Standard Deviation 1.15 |
| Part B: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | Change from Baseline in DAT at Day 14 | -1.38 score on a scale | Standard Deviation 1.25 |
| Part B: SAGE-217 Capsules | Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 | Handwriting at Baseline (Day 1) | 3.0 score on a scale | Standard Deviation 1.41 |
Comparison: Change from Baseline in Archimedes Spirals (AS) at Day 14p-value: 0.870995% CI: [-1.7, 1.9]Mixed Model for Repeated Measures (MMRM)
Comparison: Change from Baseline in Handwriting at Day 14p-value: 0.784395% CI: [-1.8, 1.4]Mixed Model for Repeated Measures (MMRM)
Comparison: Change from Baseline in Dot approximation task (DAT) at Day 14p-value: 0.760495% CI: [-2.72, 2.1]Mixed Model for Repeated Measures (MMRM)
Secondary
Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14
The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Randomization indicates improvement.
Time frame: Randomization (Day 8, predose) and Day 14 (predose)
Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 | FOPT at Randomization (Day 8) | 1.60 score on a scale | Standard Deviation 1.098 |
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 | Change from Randomization in FOPT at Day 14 | 0.03 score on a scale | Standard Deviation 0.58 |
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 | LWBPT at Randomization (Day 8) | 2.40 score on a scale | Standard Deviation 0.876 |
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 | Change from Randomization in LWBPT at Day 14 | 0.70 score on a scale | Standard Deviation 1.553 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 | Change from Randomization in LWBPT at Day 14 | 0.03 score on a scale | Standard Deviation 0.263 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 | FOPT at Randomization (Day 8) | 1.85 score on a scale | Standard Deviation 2.983 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 | LWBPT at Randomization (Day 8) | 3.15 score on a scale | Standard Deviation 3.032 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 | Change from Randomization in FOPT at Day 14 | 0.38 score on a scale | Standard Deviation 0.591 |
Comparison: Change from Randomization in Forward outstretched postural tremor (FOPT) at Day 14p-value: 0.484695% CI: [-0.65, 1.33]Mixed Model for Repeated Measures (MMRM)
Comparison: Change from Randomization in Lateral wing beating postural tremor (LWBPT) at Day 14p-value: 0.456795% CI: [-2.7, 1.36]Mixed Model for Repeated Measures (MMRM)
Secondary
Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14
The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Randomization indicates improvement.
Time frame: Randomization (Day 8, predose) and Day 14 (predose)
Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14 | Randomization (Day 8) | 7.33 score on a scale | Standard Deviation 2.373 |
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14 | Change from Randomization at Day 14 (predose) | 0.93 score on a scale | Standard Deviation 2.38 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14 | Randomization (Day 8) | 9.13 score on a scale | Standard Deviation 7.236 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14 | Change from Randomization at Day 14 (predose) | 0.55 score on a scale | Standard Deviation 0.52 |
Comparison: Change from Randomization at Day 14p-value: 0.779595% CI: [-3.47, 2.7]Mixed Model for Repeated Measures (MMRM)
Secondary
Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14
The TETRAS kinetic tremor combined score is the sum of the TETRAS Performance Subscale item 4c (kinetic tremor) scores from both sides of the body. The TETRAS kinetic tremor score ranges from 0 to 4, the total score for both sides of the body ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement.
Time frame: Randomization (Day 8, predose) and Day 14 (predose)
Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14 | Randomization (Day 8) | 2.50 score on a scale | Standard Deviation 0.577 |
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14 | Change from Randomization at Day 14 | 0.88 score on a scale | Standard Deviation 0.479 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14 | Randomization (Day 8) | 2.38 score on a scale | Standard Deviation 1.25 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14 | Change from Randomization at Day 14 | 0.38 score on a scale | Standard Deviation 0.479 |
Comparison: Change from Randomization at Day 14p-value: 0.180795% CI: [-1.17, 0.23]Mixed Model for Repeated Measures (MMRM)
Secondary
Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14
The TETRAS individual item score is the sum of the TETRAS Performance Subscale item 4a and 4b scores \[4a: forward outstretched postural tremor (FOPT) and 4b: lateral wing beating postural tremor (LWBPT) scores\] from both sides of the body. Each TETRAS score ranges from 0 to 4; the total score ranges from 0 to 16, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement.
Time frame: Randomization (Day 8, predose) and Day 14 (predose)
Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 | FOPT at Randomization (Day 8) | 2.75 score on a scale | Standard Deviation 0.5 |
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 | Change from Randomization in FOPT at Day 14 | 0.13 score on a scale | Standard Deviation 0.629 |
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 | LWBPT at Randomization (Day 8) | 2.63 score on a scale | Standard Deviation 0.479 |
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 | Change from Randomization in LWBPT at Day 14 | 0.38 score on a scale | Standard Deviation 0.629 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 | Change from Randomization in LWBPT at Day 14 | 0.25 score on a scale | Standard Deviation 0.645 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 | FOPT at Randomization (Day 8) | 2.63 score on a scale | Standard Deviation 1.702 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 | LWBPT at Randomization (Day 8) | 2.63 score on a scale | Standard Deviation 2.056 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 | Change from Randomization in FOPT at Day 14 | 0.00 score on a scale | Standard Deviation 0 |
Comparison: Change from Randomization in Forward outstretched postural tremor (FOPT) at Day 14p-value: 0.730295% CI: [-0.97, 0.69]Mixed Model for Repeated Measures (MMRM)
Comparison: Change from Randomization in Lateral wing beating postural tremor (LWBPT) at Day 14p-value: 0.791695% CI: [-1.1, 0.85]Mixed Model for Repeated Measures (MMRM)
Secondary
Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14
The TETRAS performance subscale upper limb total score is the sum of the TETRAS individual item scores from both sides of the body. The TETRAS individual item score included TETRAS Performance Subscale item 4a, 4b and 4c scores \[4a: forward outstretched postural tremor (FOPT) and 4b: lateral wing beating postural tremor (LWBPT) scores and 4c: Kinetic tremor (KT) score\] from both sides of the body. Each individual item score ranges from 0 to 4; The total upper limb score ranges from 0 to 24, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement.
Time frame: Randomization (Day 8, predose) and Day 14 (predose)
Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14 | Randomization (Day 8) | 7.88 score on a scale | Standard Deviation 1.436 |
| Part A: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14 | Change from Randomization at Day 14 | 1.38 score on a scale | Standard Deviation 1.109 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14 | Randomization (Day 8) | 7.63 score on a scale | Standard Deviation 4.956 |
| Part B: SAGE-217 Capsules | Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14 | Change from Randomization at Day 14 | 0.63 score on a scale | Standard Deviation 0.25 |
Comparison: Change from Randomization at Day 14p-value: 0.377195% CI: [-2.48, 0.96]Mixed Model for Repeated Measures (MMRM)
Secondary
Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15
The TETRAS Performance Subscale score includes 9 items. Out of these 9 items, Item 6 is Archimedes spirals (AS), Item 7 is Handwriting, and Item 8 is Dot approximation task (DAT). Each item was scored from 0 to 4, for both sides of the body, each item has a total score of 0 to 8, where higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) and Day 15
Population: The Efficacy Population consisted of all participants who completed at least 1 dose of study drug in the capsule formulation in Part C and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 | AS at Baseline (Day 1) | 4.5 score on a scale | Standard Deviation 1.97 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 | Change from Baseline in AS at Day 15 | -0.6 score on a scale | Standard Deviation 1.55 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 | Handwriting at Baseline (Day 1) | 2.4 score on a scale | Standard Deviation 1.06 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 | Change from Baseline in Handwriting at Day 15 | -0.5 score on a scale | Standard Deviation 0.74 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 | DAT at Baseline (Day 1) | 4.25 score on a scale | Standard Deviation 0.64 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 | Change from Baseline in DAT at Day 15 | -0.23 score on a scale | Standard Deviation 0.594 |
Comparison: Change from Baseline in Archimedes spirals (AS) at Day 15p-value: 0.159595% CI: [-1.5, 0.3]Mixed Model for Repeated Measures (MMRM)
Comparison: Change from Baseline in Handwriting at Day 15p-value: 0.012695% CI: [-0.9, -0.1]Mixed Model for Repeated Measures (MMRM)
Comparison: Change from Baseline in Dot approximation task (DAT) at Day 15p-value: 0.153695% CI: [-0.55, 0.1]Mixed Model for Repeated Measures (MMRM)
Secondary
Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15
The accelerometer-based Kinesia upper limb total score is the sum of Kinesia kinetic tremor scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral wing beating postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) and Day 15
Population: The Efficacy Population consisted of all participants who completed at least 1 dose of study drug in the capsule formulation in Part C and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 | FOPT at Baseline (Day 1) | 2.98 score on a scale | Standard Deviation 1.626 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 | Change from Baseline in FOPT at Day 15 | -0.53 score on a scale | Standard Deviation 1.156 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 | LWBPT at Baseline (Day 1) | 4.41 score on a scale | Standard Deviation 1.548 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 | Change from Baseline in LWBPT at Day 15 | -0.93 score on a scale | Standard Deviation 1.497 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 | Kinetic tremor at Baseline (Day 1) | 4.28 score on a scale | Standard Deviation 1.275 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 | Change from Baseline in Kinetic tremor at Day 15 | -0.51 score on a scale | Standard Deviation 1.229 |
Comparison: Change from Baseline in Forward outstretched postural tremor (FOPT) at Day 15p-value: 0.133395% CI: [-1.13, 0.17]Mixed Model for Repeated Measures (MMRM)
Comparison: Change from Baseline in Lateral wing beating postural tremor (LWBPT) at Day 15p-value: 0.057295% CI: [-1.64, 0.03]Mixed Model for Repeated Measures (MMRM)
Comparison: Change from Baseline in Kinetic tremor (KT) at Day 15p-value: 0.070795% CI: [-1.05, 0.05]Mixed Model for Repeated Measures (MMRM)
Secondary
Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15
The TETRAS individual item score is the sum of the TETRAS Performance Subscale item 4a and 4b scores \[4a: forward outstretched postural tremor (FOPT) and 4b: lateral wing beating postural tremor (LWBPT) scores\] from both sides of the body. Each TETRAS score ranges from 0 to 4; the total score ranges from 0 to 16, higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) and Day 15
Population: The Efficacy Population consisted of all participants who completed at least 1 dose of study drug in the capsule formulation in Part C and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 | FOPT at Baseline (Day 1) | 3.79 score on a scale | Standard Deviation 0.867 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 | Change from Baseline in FOPT at Day 15 | -0.13 score on a scale | Standard Deviation 1.06 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 | LWBPT at Baseline (Day 1) | 4.47 score on a scale | Standard Deviation 0.695 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 | Change from Baseline in LWBPT at Day 15 | -0.80 score on a scale | Standard Deviation 0.902 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 | Kinetic tremor at Baseline (Day 1) | 4.56 score on a scale | Standard Deviation 0.726 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 | Change from Baseline in Kinetic tremor at Day 15 | -0.67 score on a scale | Standard Deviation 0.838 |
Comparison: Change from Baseline in Forward outstretched postural tremor (FOPT) at Day 15p-value: 0.957995% CI: [-0.57, 0.54]Mixed Model for Repeated Measures (MMRM)
Comparison: Change from Baseline in Lateral wing beating postural tremor (LWBPT) at Day 15p-value: 0.003995% CI: [-1.31, -0.3]Mixed Model for Repeated Measures (MMRM)
Comparison: Change from Baseline in Kinetic tremor (KT) at Day 15p-value: 0.009995% CI: [-1.14, -0.19]Mixed Model for Repeated Measures (MMRM)
Secondary
Part C: Change From Baseline in the TETRAS Upper Limb Total Score at Day 15
The TETRAS performance subscale upper limb total score is the sum of the TETRAS individual item scores from both sides of the body. Each individual item score ranges from 0 to 4; The total upper limb score ranges from 0 to 24, higher scores indicate more severe tremor. A negative change indicates improvement.
Time frame: Baseline (Day 1) and Day 15
Population: The Efficacy Population consisted of all participants who completed at least 1 dose of study drug in the capsule formulation in Part C and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the TETRAS Upper Limb Total Score at Day 15 | Baseline (Day 1) | 12.82 score on a scale | Standard Deviation 1.952 |
| Part A: SAGE-217 Capsules | Part C: Change From Baseline in the TETRAS Upper Limb Total Score at Day 15 | Change from Baseline at Day 15 | -1.60 score on a scale | Standard Deviation 2.436 |
Comparison: Change from Baseline at Day 15p-value: 0.027895% CI: [-2.87, -0.19]Mixed Model for Repeated Measures (MMRM)
Secondary
Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS)
The SSS was designed to quickly assess how alert a subject is feeling. Degrees of sleepiness and alertness are rated on a scale of 1 to 7, where the lowest score of 1 indicates the subject is feeling active, vital, alert, or wide awake and the highest score of 7 indicates the participant is no longer fighting sleep, sleep onset soon; having dream-like thoughts. Greater changes from baseline indicate greater sedation. A positive change from baseline indicates improvement.
Time frame: Baseline (Day 1), Day 7 (predose) for Part A, Day 14 (predose) for Part B
Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B). Number analyzed is the number of participants with data available for analysis at the given time point. SSS was not evaluated in Part C.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS) | Baseline (Day 1) | 2.1 score on a scale | Standard Deviation 1.41 |
| Part A: SAGE-217 Capsules | Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS) | Change from Baseline at Day 7 or 14 | -0.2 score on a scale | Standard Deviation 1.42 |
| Part B: SAGE-217 Capsules | Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS) | Baseline (Day 1) | 1.5 score on a scale | Standard Deviation 0.58 |
| Part B: SAGE-217 Capsules | Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS) | Change from Baseline at Day 7 or 14 | -0.5 score on a scale | Standard Deviation 0.58 |
| Part B: Placebo | Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS) | Baseline (Day 1) | 2.3 score on a scale | Standard Deviation 1.26 |
| Part B: Placebo | Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS) | Change from Baseline at Day 7 or 14 | -0.5 score on a scale | Standard Deviation 0.58 |
Secondary
Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score
Mood was assessed using the Bond-Lader VAS score. This is a 16-part self-administered questionnaire that employs a 100-mm VAS to explore different aspects of self-reported mood. Three factor scores for (alertness, contentedness, and calmness) were calculated using following equations based on normalized VAS scores: * Alertness = 0.827X1 + 0.618X3 + 0.755X4 + 0.642X5 + 0.776X6 + 0.635X9 + 0.792X11 + 0.593X12 + 0.614X15; * Contentedness = 0.677X7 + 0.697X8 + 0.823X13 + 0.738X14 + 0.594X16; and * Calmness = 0.845X2 + 0.677X10, where Xi represents a subject's item score after normalization, and i represents the item number from the entire scale (in order from 1-16). A negative change from baseline (CFB) indicated more alertness, more contentedness, and more calmness.
Time frame: Baseline (Day 1), Day 7 (predose) for Part A, Day 14 (predose) for Part B and Day 15 for Part C
Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B). Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Alertness: Baseline (Day 1) | 18.737 log(units on a scale) | Standard Deviation 3.864 |
| Part A: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Alertness: CFB at Day 7, 14 or 15 | -0.148 log(units on a scale) | Standard Deviation 6.4794 |
| Part A: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Contentedness: Baseline (Day 1) | 10.281 log(units on a scale) | Standard Deviation 2.7813 |
| Part A: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Contentedness: CFB at Day 7, 14 or 15 | -0.121 log(units on a scale) | Standard Deviation 3.1249 |
| Part A: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Calmness: Baseline (Day 1) | 4.589 log(units on a scale) | Standard Deviation 1.274 |
| Part A: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Calmness: CFB at Day 7, 14 or 15 | 0.304 log(units on a scale) | Standard Deviation 1.4579 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Calmness: CFB at Day 7, 14 or 15 | -0.613 log(units on a scale) | Standard Deviation 0.4106 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Contentedness: CFB at Day 7, 14 or 15 | -1.896 log(units on a scale) | Standard Deviation 2.2236 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Alertness: Baseline (Day 1) | 18.345 log(units on a scale) | Standard Deviation 3.2388 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Contentedness: Baseline (Day 1) | 11.284 log(units on a scale) | Standard Deviation 0.215 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Alertness: CFB at Day 7, 14 or 15 | -2.857 log(units on a scale) | Standard Deviation 1.6712 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Calmness: Baseline (Day 1) | 5.446 log(units on a scale) | Standard Deviation 0.772 |
| Part B: Placebo | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Alertness: CFB at Day 7, 14 or 15 | -1.038 log(units on a scale) | Standard Deviation 4.6404 |
| Part B: Placebo | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Contentedness: Baseline (Day 1) | 12.545 log(units on a scale) | Standard Deviation 1.7398 |
| Part B: Placebo | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Contentedness: CFB at Day 7, 14 or 15 | -0.471 log(units on a scale) | Standard Deviation 2.5222 |
| Part B: Placebo | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Calmness: CFB at Day 7, 14 or 15 | -0.601 log(units on a scale) | Standard Deviation 1.4341 |
| Part B: Placebo | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Calmness: Baseline (Day 1) | 5.344 log(units on a scale) | Standard Deviation 0.7802 |
| Part B: Placebo | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Alertness: Baseline (Day 1) | 21.308 log(units on a scale) | Standard Deviation 2.7694 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Calmness: Baseline (Day 1) | 5.6157 log(units on a scale) | Standard Deviation 0.89826 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Calmness: CFB at Day 7, 14 or 15 | -0.5116 log(units on a scale) | Standard Deviation 1.23403 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Alertness: CFB at Day 7, 14 or 15 | 1.3095 log(units on a scale) | Standard Deviation 5.87702 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Contentedness: CFB at Day 7, 14 or 15 | 0.0881 log(units on a scale) | Standard Deviation 3.16922 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Alertness: Baseline (Day 1) | 18.1248 log(units on a scale) | Standard Deviation 4.62487 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score | Contentedness: Baseline (Day 1) | 9.8911 log(units on a scale) | Standard Deviation 3.53165 |
Secondary
Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE)
An Adverse Event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. Adverse events that occurred after the first administration of study drug were denoted as TEAEs. A Serious Adverse Event (SAE) was an AE occurring during any study phase and at any dose of the study drug, comparator, or placebo, that fulfilled the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Time frame: From first dose of study drug through 14 days after the last dose (Up to 28 days)
Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: SAGE-217 Capsules | Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | At Least One TEAE | 2 Participants |
| Part A: SAGE-217 Capsules | Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | SAE | 1 Participants |
| Part B: SAGE-217 Capsules | Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | At Least One TEAE | 7 Participants |
| Part B: SAGE-217 Capsules | Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | SAE | 0 Participants |
| Part B: Placebo | Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | At Least One TEAE | 0 Participants |
| Part B: Placebo | Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | SAE | 0 Participants |
| Part B: SAGE-217 Capsules | Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | SAE | 0 Participants |
| Part B: SAGE-217 Capsules | Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | At Least One TEAE | 1 Participants |
| Part C: SAGE-217 Capsules | Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | At Least One TEAE | 10 Participants |
| Part C: SAGE-217 Capsules | Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) | SAE | 0 Participants |
Secondary
Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score
Participants responded to 5 DEQs based on how they are feeling after taking the study drug. DEQ-5 were as follows; Q1: Do you FEEL a drug effect right now? Q2: Are you HIGH right now? Q3: Do you DISLIKE any of the effects that you are feeling right now? Q4: Do you LIKE any of the effects that you are feeling right now? Q5: Would you like MORE of the drug you took, right now? The answers were recorded on a 100-mm VAS, with the answer for each being Not at all (0 mm) and Extremely (100 mm) at the extremes. There were options to record Not applicable for questions 3 and 4 if no drug effects were felt and for question 5 prior to administration of study medication, and these participants were excluded from the data summarization. Higher score on Q1 indicates a drug effect; on Q2 indicates feeling high; on Q3 indicates disliking the drug; and on Q4 and Q5 indicates liking the drug.
Time frame: Baseline (Day 1), Day 7 (2 hours postdose) for Part A, Day 14 (2 hours postdose) for Part B and Day 15 for Part C
Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B). Number analyzed is the number of participants with data available for analysis at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q4: Day 7, 14 or 15 | 30.0 units on a scale | Standard Deviation 19.65 |
| Part A: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q2: Day 7, 14 or 15 | 21.4 units on a scale | Standard Deviation 22.56 |
| Part A: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q5: Day 7, 14 or 15 | 34.5 units on a scale | Standard Deviation 26.13 |
| Part A: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q3: Day 7, 14 or 15 | 47.5 units on a scale | Standard Deviation 30.63 |
| Part A: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q1: Day 7, 14 or 15 | 54.8 units on a scale | Standard Deviation 27.56 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q3: Day 7, 14 or 15 | 12.0 units on a scale | Standard Deviation 7.83 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q4: Day 7, 14 or 15 | 33.5 units on a scale | Standard Deviation 32.25 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q5: Day 7, 14 or 15 | 17.8 units on a scale | Standard Deviation 18.61 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q2: Day 7, 14 or 15 | 18.0 units on a scale | Standard Deviation 21.65 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q1: Day 7, 14 or 15 | 22.5 units on a scale | Standard Deviation 18.84 |
| Part B: Placebo | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q3: Day 7, 14 or 15 | 46.3 units on a scale | Standard Deviation 24.85 |
| Part B: Placebo | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q1: Day 7, 14 or 15 | 33.0 units on a scale | Standard Deviation 28.23 |
| Part B: Placebo | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q2: Day 7, 14 or 15 | 24.5 units on a scale | Standard Deviation 21.44 |
| Part B: Placebo | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q4: Day 7, 14 or 15 | 33.0 units on a scale | Standard Deviation 17.44 |
| Part B: Placebo | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q5: Day 7, 14 or 15 | 23.0 units on a scale | Standard Deviation 20.12 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q4: Day 7, 14 or 15 | 38.3 units on a scale | Standard Deviation 32.48 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q2: Day 7, 14 or 15 | 13.3 units on a scale | Standard Deviation 19.72 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q1: Day 7, 14 or 15 | 27.9 units on a scale | Standard Deviation 24.57 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q3: Day 7, 14 or 15 | 35.2 units on a scale | Standard Deviation 37.04 |
| Part B: SAGE-217 Capsules | Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score | Q5: Day 7, 14 or 15 | 34.6 units on a scale | Standard Deviation 31.11 |