A Study to Evaluate SAGE-217 in Participants With Essential Tremor

• Sponsor: Sage Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02978781
• Collaborator: (none)
• Enrollment: 34
• Locations: 26
• Arms: 5
• Actual Duration (Months): 8.4
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Essential Tremor	Drug: SAGE-217; Drug: SAGE-217; Drug: Placebo	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of SAGE-217 in the Treatment of Subjects With Essential Tremor
• Actual Study Start Date: Mar 24, 2017
• Actual Primary Completion Date: Nov 22, 2017
• Actual Study Completion Date: Dec 5, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: SAGE-217 Oral Solution Participants received SAGE-217 10 mg oral solution on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 with food in the morning.	Drug: SAGE-217; SAGE-217 Oral Solution
Experimental: Part A: SAGE-217 Capsules Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.	Drug: SAGE-217; SAGE-217 Capsules
Placebo Comparator: Part B: Placebo Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.	Drug: Placebo; SAGE-217 matching placebo capsules
Experimental: Part B: SAGE-217 Capsules Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.	Drug: SAGE-217; SAGE-217 Capsules
Experimental: Part C: SAGE-217 Capsules Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).	Drug: SAGE-217; SAGE-217 Capsules

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. Number of Participants With Clinically Significant Vital Signs [Up to 28 days]

    Vital signs included heart rate, respiratory rate, temperature, and blood pressure.

19. Number of Participants With Clinically Significant Laboratory Parameters [Up to 28 days]

    Laboratory parameters included hematology, blood chemistry, and urinalysis.

20. Number of Participants With Clinically Significant Electrocardiogram (ECG) Values [Up to 28 days]

    A 12-lead ECG was performed.

21. 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.

22. 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.

23. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sage Investigational Site	Anniston	Alabama	United States	36207
2	Sage Investigational Site	Little Rock	Arkansas	United States	72211
3	Sage Investigational Site	Rogers	Arkansas	United States	72758
4	Sage Investigational Site	Cerritos	California	United States	90703
5	Sage Investigational Site	Fountain Valley	California	United States	92708
6	Sage Investigational Site	Oceanside	California	United States	92056
7	Sage Investigational Site	San Diego	California	United States	92103
8	Sage Investigational Site	Englewood	Colorado	United States	80113
9	Sage Investigational Site	Clearwater	Florida	United States	33756
10	Sage Investigational Site	DeLand	Florida	United States	32720
11	Sage Investigational Site	Lauderdale Lakes	Florida	United States	33319
12	Sage Investigational Site	Orlando	Florida	United States	32806
13	Sage Investigational Site	Ormond Beach	Florida	United States	32174
14	Sage Investigational Site	Saint Petersburg	Florida	United States	33713
15	Sage Investigational Site	Tampa	Florida	United States	33612
16	Sage Investigational Site	Atlanta	Georgia	United States	30331
17	Sage Investigational Site	Decatur	Georgia	United States	30030
18	Sage Investigational Site	Chicago	Illinois	United States	60612
19	Sage Investigational Site	Urbana	Illinois	United States	61801
20	Sage Investigational Site	Saint Louis	Missouri	United States	63141
21	Sage Investigational Site	Springfield	Missouri	United States	65802
22	Sage Investigational Site	Raleigh	North Carolina	United States	27612
23	Sage Investigational Site	Cincinnati	Ohio	United States	45212
24	Sage Investigational Site	Dayton	Ohio	United States	45417
25	Sage Investigational Site	Nashville	Tennessee	United States	37232
26	Sage Investigational Site	Fort Worth	Texas	United States	76104

Sponsors and Collaborators

• Sage Therapeutics

Investigators

• Study Director: Christopher Silber, MD, Sage Therapeutics

Study Documents (Full-Text)

• Study Protocol - Sep 5, 2017
• Statistical Analysis Plan - Dec 14, 2017

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT02978781
• Other Study ID Numbers: 217-ETD-201
• First Posted: Dec 1, 2016
• Last Update Posted: Jan 27, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sage Therapeutics: Tremor
• Additional relevant MeSH terms: Tremor; Essential Tremor

Study Results

Participant Flow

Recruitment Details	A total of 34 participants were enrolled in the study from 11 investigation sites in United States.
Pre-assignment Detail	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.

Arm/Group Title	Part A: SAGE-217 Oral Solution	Part A: SAGE-217 Capsules	Part B: Placebo	Part B: SAGE-217 Capsules	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg oral solution on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 with food in the morning.	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response (≥30% reduction in kinetic tremor) on Day 8 were randomized to receive SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning. Participants received placebo capsules to match their maximum tolerated SAGE-217 dose as determined in Part A.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive maximum tolerated SAGE-217 in Part A for 7 days beginning on Day 8 with food in the morning. Participants received their maximum tolerated SAGE-217 dose as determined in Part A.	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).
Period Title: Part A
STARTED	2	14	0	0	0
COMPLETED	1	12	0	0	0
NOT COMPLETED	1	2	0	0	0
Period Title: Part A
STARTED	0	0	4	4	0
COMPLETED	0	0	4	3	0
NOT COMPLETED	0	0	0	1	0
Period Title: Part A
STARTED	0	0	0	0	18
COMPLETED	0	0	0	0	14
NOT COMPLETED	0	0	0	0	4

Baseline Characteristics

Arm/Group Title	Part A: SAGE-217 Oral Solution	Part A: SAGE-217 Capsules	Part C: SAGE-217 Capsules	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	2	14	18	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.5 (0.71)	62.4 (8.34)	65.8 (8.21)	64.7 (8.24)
Sex: Female, Male (Count of Participants)
Female	1 50%	7 50%	10 55.6%	18 52.9%
Male	1 50%	7 50%	8 44.4%	16 47.1%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	1 50%	3 21.4%	0 0%	4 11.8%
White	1 50%	11 78.6%	18 100%	30 88.2%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino	2 100%	14 100%	18 100%	34 100%
Region of Enrollment (participants) [Number]
United States	2 100%	14 100%	18 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.
Measure Participants	14
Baseline (Day 1)	4.36 (1.199)
Change from Baseline at Day 7 (8 hours postdose)	-0.69 (1.115)

2. Primary Outcome

Title	Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part B: Placebo	Part B: SAGE-217 Capsules
Arm/Group Description	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning. Participants received placebo capsules to match their maximum tolerated SAGE-217 dose as determined in Part A.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 for 7 days beginning on Day 8 with food in the morning. Participants received their maximum tolerated SAGE-217 dose as determined in Part A.
Measure Participants	4	4
Randomization (Day 8)	3.33 (0.714)	4.13 (1.438)
Change from Randomization at Day 14 (predose)	0.20 (0.271)	0.15 (0.191)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Randomization at Day 14 (predose)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9143
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.44 to 0.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.227
	Estimation Comments	Least squares mean difference from Randomization (SAGE-217 - placebo)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

3. Primary Outcome

Title	Part C: Change From Baseline in the Accelerometer-based Kinesia Upper Limb Tremor Combined Score at Day 15
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).
Measure Participants	16
Baseline (Day 1)	11.68 (3.822)
Change from Baseline at Day 15	-2.22 (2.956)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0529
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.74
	Confidence Interval	(2-Sided) 95%; -3.50 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.815
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

4. Secondary Outcome

Title	Part A: Change From Baseline in Kinesia Upper Limb Total Score at Day 7
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.
Measure Participants	14
Baseline (Day 1)	10.50 (4.395)
Change from Baseline at Day 7 (8 hours postdose)	-2.40 (3.395)

5. Secondary Outcome

Title	Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7
Description	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])

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.
Measure Participants	14
FOPT at Baseline (Day 1)	2.51 (1.749)
Change from Baseline in FOPT at Day 7 (8 hr pd)	-0.74 (1.339)
LWBPT at Baseline (Day 1)	3.63 (1.695)
Change from Baseline in LWBPT at Day 7 (8 hr pd)	-0.97 (1.312)
Kinetic tremor at Baseline (Day 1)	4.36 (1.199)

6. Secondary Outcome

Title	Part A: Change From Baseline in the Tremor Research Group (TRG) Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Total Score at Day 7
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.
Measure Participants	14
Baseline (Day 1)	12.86 (2.373)
Change from Baseline at Day 7	-4.42 (2.964)

7. Secondary Outcome

Title	Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.
Measure Participants	14
FOPT at Baseline (Day 1)	4.14 (0.989)
Change from Baseline in FOPT at Day 7	-1.46 (1.070)
LWBPT at Baseline (Day 1)	4.18 (0.932)
Change from Baseline in LWBPT at Day 7	-1.31 (1.011)
Kinetic Tremor at Baseline (Day 1)	4.54 (0.720)
Change from Baseline in Kinetic Tremor at Day 7	-1.65 (1.179)

8. Secondary Outcome

Title	Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.
Measure Participants	14
AS at Baseline (Day 1)	4.8 (1.37)
Change from Baseline in AS at Day 7	-1.0 (1.29)
Handwriting at Baseline (Day 1)	2.3 (1.07)
Change from Baseline in Handwriting at Day 7	-0.4 (0.77)
DAT at Baseline (Day 1)	4.46 (0.692)
Change from Baseline in DAT at Day 7	-0.96 (0.967)

9. Secondary Outcome

Title	Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part B: Placebo	Part B: SAGE-217 Capsules
Arm/Group Description	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning. Participants received placebo capsules to match their maximum tolerated SAGE-217 dose as determined in Part A.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 for 7 days beginning on Day 8 with food in the morning. Participants received their maximum tolerated SAGE-217 dose as determined in Part A.
Measure Participants	4	4
Randomization (Day 8)	7.33 (2.373)	9.13 (7.236)
Change from Randomization at Day 14 (predose)	0.93 (2.380)	0.55 (0.520)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Randomization at Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7795
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -3.47 to 2.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.326
	Estimation Comments	Least squares mean difference from Randomization (SAGE-217 - placebo)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

10. Secondary Outcome

Title	Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part B: Placebo	Part B: SAGE-217 Capsules
Arm/Group Description	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning. Participants received placebo capsules to match their maximum tolerated SAGE-217 dose as determined in Part A.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 for 7 days beginning on Day 8 with food in the morning. Participants received their maximum tolerated SAGE-217 dose as determined in Part A.
Measure Participants	4	4
FOPT at Randomization (Day 8)	1.60 (1.098)	1.85 (2.983)
Change from Randomization in FOPT at Day 14	0.03 (0.580)	0.38 (0.591)
LWBPT at Randomization (Day 8)	2.40 (0.876)	3.15 (3.032)
Change from Randomization in LWBPT at Day 14	0.70 (1.553)	0.03 (0.263)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Randomization in Forward outstretched postural tremor (FOPT) at Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4846
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -0.65 to 1.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.473
	Estimation Comments	Least squares mean difference from Randomization (SAGE-217 - placebo)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Randomization in Lateral "wing beating" postural tremor (LWBPT) at Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4567
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -2.70 to 1.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.845
	Estimation Comments	Least squares mean difference from Randomization (SAGE-217 - placebo)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

11. Secondary Outcome

Title	Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part B: Placebo	Part B: SAGE-217 Capsules
Arm/Group Description	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning. Participants received placebo capsules to match their maximum tolerated SAGE-217 dose as determined in Part A.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 for 7 days beginning on Day 8 with food in the morning. Participants received their maximum tolerated SAGE-217 dose as determined in Part A.
Measure Participants	4	4
Randomization (Day 8)	7.88 (1.436)	7.63 (4.956)
Change from Randomization at Day 14	1.38 (1.109)	0.63 (0.250)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Randomization at Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3771
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95%; -2.48 to 0.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.850
	Estimation Comments	Least squares mean difference from Randomization (SAGE-217 - placebo)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

12. Secondary Outcome

Title	Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part B: Placebo	Part B: SAGE-217 Capsules
Arm/Group Description	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning. Participants received placebo capsules to match their maximum tolerated SAGE-217 dose as determined in Part A.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 for 7 days beginning on Day 8 with food in the morning. Participants received their maximum tolerated SAGE-217 dose as determined in Part A.
Measure Participants	4	4
FOPT at Randomization (Day 8)	2.75 (0.500)	2.63 (1.702)
Change from Randomization in FOPT at Day 14	0.13 (0.629)	0.00 (0.000)
LWBPT at Randomization (Day 8)	2.63 (0.479)	2.63 (2.056)
Change from Randomization in LWBPT at Day 14	0.38 (0.629)	0.25 (0.645)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Randomization in Forward outstretched postural tremor (FOPT) at Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7302
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.97 to 0.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.415
	Estimation Comments	Least squares mean difference from Randomization (SAGE-217 - placebo)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Randomization in Lateral "wing beating" postural tremor (LWBPT) at Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7916
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -1.10 to 0.85
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.467
	Estimation Comments	Least squares mean difference from Randomization (SAGE-217 - placebo)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

13. Secondary Outcome

Title	Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part B: Placebo	Part B: SAGE-217 Capsules
Arm/Group Description	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning. Participants received placebo capsules to match their maximum tolerated SAGE-217 dose as determined in Part A.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 for 7 days beginning on Day 8 with food in the morning. Participants received their maximum tolerated SAGE-217 dose as determined in Part A.
Measure Participants	4	4
Randomization (Day 8)	2.50 (0.577)	2.38 (1.250)
Change from Randomization at Day 14	0.88 (0.479)	0.38 (0.479)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Randomization at Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1807
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95%; -1.17 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.340
	Estimation Comments	Least squares mean difference from Randomization (SAGE-217 - placebo)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

14. Secondary Outcome

Title	Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part B: Placebo	Part B: SAGE-217 Capsules
Arm/Group Description	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning. Participants received placebo capsules to match their maximum tolerated SAGE-217 dose as determined in Part A.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 for 7 days beginning on Day 8 with food in the morning. Participants received their maximum tolerated SAGE-217 dose as determined in Part A.
Measure Participants	4	4
AS at Baseline (Day 1)	5.0 (0.82)	5.3 (1.89)
Change from Baseline in AS at Day 14	-1.3 (0.96)	-1.0 (1.15)
Handwriting at Baseline (Day 1)	2.3 (0.96)	3.0 (1.41)
Change from Baseline in Handwriting at Day 14	-0.5 (1.00)	-0.5 (0.58)
DAT at Baseline (Day 1)	4.63 (0.629)	4.50 (1.000)
Change from Baseline in DAT at Day 14	-1.25 (0.866)	-1.38 (1.250)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Baseline in Archimedes Spirals (AS) at Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8709
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -1.7 to 1.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.72
	Estimation Comments	Least squares mean difference from Baseline(SAGE-217 - placebo)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Baseline in Handwriting at Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7843
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.8 to 1.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.65
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217 - placebo)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules, Part B: SAGE-217 Capsules
	Comments	Change from Baseline in Dot approximation task (DAT) at Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7604
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -2.72 to 2.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.984
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217 - placebo
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

15. Secondary Outcome

Title	Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).
Measure Participants	16
FOPT at Baseline (Day 1)	2.98 (1.626)
Change from Baseline in FOPT at Day 15	-0.53 (1.156)
LWBPT at Baseline (Day 1)	4.41 (1.548)
Change from Baseline in LWBPT at Day 15	-0.93 (1.497)
Kinetic tremor at Baseline (Day 1)	4.28 (1.275)
Change from Baseline in Kinetic tremor at Day 15	-0.51 (1.229)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline in Forward outstretched postural tremor (FOPT) at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1333
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -1.13 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.301
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline in Lateral "wing beating" postural tremor (LWBPT) at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0572
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.81
	Confidence Interval	(2-Sided) 95%; -1.64 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.389
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline in Kinetic tremor (KT) at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0707
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -1.05 to 0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.255
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

16. Secondary Outcome

Title	Part C: Change From Baseline in the TETRAS Upper Limb Total Score at Day 15
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).
Measure Participants	17
Baseline (Day 1)	12.82 (1.952)
Change from Baseline at Day 15	-1.60 (2.436)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0278
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.53
	Confidence Interval	(2-Sided) 95%; -2.87 to -0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.628
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

17. Secondary Outcome

Title	Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).
Measure Participants	17
FOPT at Baseline (Day 1)	3.79 (0.867)
Change from Baseline in FOPT at Day 15	-0.13 (1.060)
LWBPT at Baseline (Day 1)	4.47 (0.695)
Change from Baseline in LWBPT at Day 15	-0.80 (0.902)
Kinetic tremor at Baseline (Day 1)	4.56 (0.726)
Change from Baseline in Kinetic tremor at Day 15	-0.67 (0.838)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline in Forward outstretched postural tremor (FOPT) at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9579
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.57 to 0.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.258
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline in Lateral "wing beating" postural tremor (LWBPT) at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -1.31 to -0.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.234
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline in Kinetic tremor (KT) at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0099
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -1.14 to -0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.223
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

18. Secondary Outcome

Title	Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).
Measure Participants	17
AS at Baseline (Day 1)	4.5 (1.97)
Change from Baseline in AS at Day 15	-0.6 (1.55)
Handwriting at Baseline (Day 1)	2.4 (1.06)
Change from Baseline in Handwriting at Day 15	-0.5 (0.74)
DAT at Baseline (Day 1)	4.25 (0.640)
Change from Baseline in DAT at Day 15	-0.23 (0.594)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline in Archimedes spirals (AS) at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1595
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline in Handwriting at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0126
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: SAGE-217 Capsules
	Comments	Change from Baseline in Dot approximation task (DAT) at Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1536
	Comments
	Method	Mixed Model for Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -0.55 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.151
	Estimation Comments	Least squares mean difference from Baseline (SAGE-217)
Other Statistical Analysis		MMRM model was used for analysis with change from randomization of the Kinesia kinetic tremor combined scores as the dependent variable, treatment group by study visit/time point interaction as fixed effects, and randomization value as a covariate.

19. Secondary Outcome

Title	Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Oral Solution	Part A: SAGE-217 Capsules	Part B: Placebo	Part B: SAGE-217 Capsules	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg oral solution on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 with food in the morning.	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning. Participants received placebo capsules to match their maximum tolerated SAGE-217 dose as determined in Part A.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 for 7 days beginning on Day 8 with food in the morning. Participants received their maximum tolerated SAGE-217 dose as determined in Part A.	Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).
Measure Participants	2	14	4	4	18
At Least One TEAE	2 100%	7 50%	0 0%	1 2.9%	10 NaN
SAE	1 50%	0 0%	0 0%	0 0%	0 NaN

20. Secondary Outcome

Title	Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Oral Solution	Part A: SAGE-217 Capsules	Part B: Placebo	Part B: SAGE-217 Capsules	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 as an oral solution with food in the morning.	Participants in Part A 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.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning. Participants received placebo capsules to match their maximum tolerated SAGE-217 dose as determined in Part A.	Participants who tolerated a ≥10 mg dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive SAGE-217 for 7 days beginning on Day 8 with food in the morning. Participants received their maximum tolerated SAGE-217 dose as determined in Part A.	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 Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Measure Participants	2	14	4	4	18
Wish to be Dead (baseline)	0 0%	0 0%	1 5.6%	0 0%	0 NaN
Wish to be Dead (PB)	0 0%	0 0%	1 5.6%	0 0%	0 NaN
Non-Specific Active Suicidal Thoughts (baseline)	0 0%	0 0%	0 0%	0 0%	0 NaN
Non-Specific Active Suicidal Thoughts (PB)	0 0%	0 0%	0 0%	0 0%	0 NaN

21. Secondary Outcome

Title	Number of Participants With Clinically Significant Vital Signs
Description	Vital signs included heart rate, respiratory rate, temperature, and blood pressure.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Oral Solution	Part A: SAGE-217 Capsules	Part B: Placebo	Part B: SAGE-217 Capsules	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 as an oral solution with food in the morning.	Participants in Part A 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.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.	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 Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Measure Participants	2	14	4	4	18
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 NaN

22. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Parameters
Description	Laboratory parameters included hematology, blood chemistry, and urinalysis.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Oral Solution	Part A: SAGE-217 Capsules	Part B: Placebo	Part B: SAGE-217 Capsules	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 as an oral solution with food in the morning.	Participants in Part A 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.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.	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 Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Measure Participants	2	14	4	4	18
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 NaN

23. Secondary Outcome

Title	Number of Participants With Clinically Significant Electrocardiogram (ECG) Values
Description	A 12-lead ECG was performed.
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Oral Solution	Part A: SAGE-217 Capsules	Part B: Placebo	Part B: SAGE-217 Capsules	Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 as an oral solution with food in the morning.	Participants in Part A 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.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.	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 Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Measure Participants	2	14	4	4	18
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 NaN

24. Secondary Outcome

Title	Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217	Part B: Placebo	Part B: SAGE-217 Capsules
Arm/Group Description	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.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.
Measure Participants	14	4	4
Baseline (Day 1)	2.1 (1.41)	1.5 (0.58)	2.3 (1.26)
Change from Baseline at Day 7 or 14	-0.2 (1.42)	-0.5 (0.58)	-0.5 (0.58)

25. Secondary Outcome

Title	Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Capsules	Part B: Placebo	Part B: SAGE-217 Capsules	Part C: SAGE-217 Capsules
Arm/Group Description	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.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.	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 Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Measure Participants	14	4	4	18
Alertness: Baseline (Day 1)	18.737 (3.8640)	18.345 (3.2388)	21.308 (2.7694)	18.1248 (4.62487)
Alertness: CFB at Day 7, 14 or 15	-0.148 (6.4794)	-2.857 (1.6712)	-1.038 (4.6404)	1.3095 (5.87702)
Contentedness: Baseline (Day 1)	10.281 (2.7813)	11.284 (0.2150)	12.545 (1.7398)	9.8911 (3.53165)
Contentedness: CFB at Day 7, 14 or 15	-0.121 (3.1249)	-1.896 (2.2236)	-0.471 (2.5222)	0.0881 (3.16922)
Calmness: Baseline (Day 1)	4.589 (1.2740)	5.446 (0.7720)	5.344 (0.7802)	5.6157 (0.89826)
Calmness: CFB at Day 7, 14 or 15	0.304 (1.4579)	-0.613 (0.4106)	-0.601 (1.4341)	-0.5116 (1.23403)

26. Secondary Outcome

Title	Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Part A: SAGE-217 Capsules	Part B: Placebo	Part B: SAGE-217 Capsules	Part C: SAGE-217 Capsules
Arm/Group Description	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.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.	Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.	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 Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Measure Participants	14	4	4	18
Q1: Day 7, 14 or 15	54.8 (27.56)	22.5 (18.84)	33.0 (28.23)	27.9 (24.57)
Q2: Day 7, 14 or 15	21.4 (22.56)	18.0 (21.65)	24.5 (21.44)	13.3 (19.72)
Q3: Day 7, 14 or 15	47.5 (30.63)	12.0 (7.83)	46.3 (24.85)	35.2 (37.04)
Q4: Day 7, 14 or 15	30.0 (19.65)	33.5 (32.25)	33.0 (17.44)	38.3 (32.48)
Q5: Day 7, 14 or 15	34.5 (26.13)	17.8 (18.61)	23.0 (20.12)	34.6 (31.11)

Adverse Events

Time Frame	TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days).
Adverse Event Reporting Description	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/Group Title	Part A: SAGE-217 Oral Solution		Part A: SAGE-217 Capsules		Part B: Placebo		Part B: SAGE-217 Capsules		Part C: SAGE-217 Capsules
Arm/Group Description	Participants received SAGE-217 10 mg on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 as an oral solution with food in the morning.		Participants in Part A 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.		Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.		Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.		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 Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
All Cause Mortality
	Part A: SAGE-217 Oral Solution		Part A: SAGE-217 Capsules		Part B: Placebo		Part B: SAGE-217 Capsules		Part C: SAGE-217 Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		0/18 (0%)
Serious Adverse Events
	Part A: SAGE-217 Oral Solution		Part A: SAGE-217 Capsules		Part B: Placebo		Part B: SAGE-217 Capsules		Part C: SAGE-217 Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		0/18 (0%)
Psychiatric disorders
Confusional state	1/2 (50%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Part A: SAGE-217 Oral Solution		Part A: SAGE-217 Capsules		Part B: Placebo		Part B: SAGE-217 Capsules		Part C: SAGE-217 Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		7/14 (50%)		0/4 (0%)		1/4 (25%)		10/18 (55.6%)
Blood and lymphatic system disorders
Neutropenia	0/2 (0%)		1/14 (7.1%)		0/4 (0%)		0/4 (0%)		0/18 (0%)
Eye disorders
Diplopia	0/2 (0%)		1/14 (7.1%)		0/4 (0%)		0/4 (0%)		0/18 (0%)
Gastrointestinal disorders
Paraesthesia oral	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)
General disorders
Asthenia	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)
Gait disturbance	0/2 (0%)		0/14 (0%)		0/4 (0%)		1/4 (25%)		0/18 (0%)
Infections and infestations
Conjunctivitis	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)
Gastric infection	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)
Nervous system disorders
Dizziness	2/2 (100%)		3/14 (21.4%)		0/4 (0%)		0/4 (0%)		4/18 (22.2%)
Somnolence	1/2 (50%)		4/14 (28.6%)		0/4 (0%)		0/4 (0%)		5/18 (27.8%)
Sedation	1/2 (50%)		2/14 (14.3%)		0/4 (0%)		0/4 (0%)		2/18 (11.1%)
Amnesia	0/2 (0%)		1/14 (7.1%)		0/4 (0%)		0/4 (0%)		0/18 (0%)
Bradykinesia	0/2 (0%)		1/14 (7.1%)		0/4 (0%)		0/4 (0%)		0/18 (0%)
Muscle contractions involuntary	1/2 (50%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		0/18 (0%)
Depressed level of consciousness	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)
Headache	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)
Psychiatric disorders
Somnambulism	1/2 (50%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		0/18 (0%)
Anxiety	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)
Disorientation	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)
Insomnia	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)
Nervousness	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)
Skin and subcutaneous tissue disorders
Skin irritation	0/2 (0%)		1/14 (7.1%)		0/4 (0%)		0/4 (0%)		0/18 (0%)
Petechiae	0/2 (0%)		0/14 (0%)		0/4 (0%)		0/4 (0%)		1/18 (5.6%)

Limitations/Caveats

Parts A and B were stopped early (in advance of the planned sample size).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PI can either be a party and subject to the same restrictions as the institution, or if not a party, the restrictions are described on the face of the contract (i.e., PI is a contractor of the institution; PI is part of a larger group of study personnel; institution has contracted with or otherwise bound all study personnel under confidentiality obligations and requirements to vest intellectual property to the institution).