Trial Outcomes & Findings for A Study to Evaluate SAGE-217 in Participants With Essential Tremor (NCT NCT02978781)

NCT ID: NCT02978781

Last Updated: 2023-11-28

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 34 participants
• Primary outcome timeframe: Baseline (Day 1) and Day 7 (8 hours postdose)
• Results posted on: 2023-11-28

Participant Flow

A total of 34 participants were enrolled in the study from 11 investigation sites in United States.

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.

Participant milestones

Measure	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.	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.	Part B: Placebo 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.	Part B: SAGE-217 Capsules 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.	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).
Part A STARTED	2	14	0	0	0
Part A COMPLETED	1	12	0	0	0
Part A NOT COMPLETED	1	2	0	0	0
Part B STARTED	0	0	4	4	0
Part B COMPLETED	0	0	4	3	0
Part B NOT COMPLETED	0	0	0	1	0
Part C STARTED	0	0	0	0	18
Part C COMPLETED	0	0	0	0	14
Part C NOT COMPLETED	0	0	0	0	4

Reasons for withdrawal

Measure	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.	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.	Part B: Placebo 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.	Part B: SAGE-217 Capsules 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.	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).
Part A Adverse Event	1	1	0	0	0
Part A Withdrawal by Subject	0	1	0	0	0
Part B Withdrawal by Subject	0	0	0	1	0
Part C Adverse Event	0	0	0	0	2
Part C Withdrawal by Subject	0	0	0	0	1
Part C Tremor not improved due to Topamax discontinuation	0	0	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Part A: SAGE-217 Oral Solution n=2 Participants 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.	Part A: SAGE-217 Capsules n=14 Participants 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.	Part C: SAGE-217 Capsules n=18 Participants 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 n=34 Participants Total of all reporting groups
Age, Continuous	71.5 years STANDARD_DEVIATION 0.71 • n=5 Participants	62.4 years STANDARD_DEVIATION 8.34 • n=7 Participants	65.8 years STANDARD_DEVIATION 8.21 • n=5 Participants	64.7 years STANDARD_DEVIATION 8.24 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	18 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	16 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized White	1 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants	30 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	2 Participants n=5 Participants	14 Participants n=7 Participants	18 Participants n=5 Participants	34 Participants n=4 Participants
Region of Enrollment United States	2 participants n=5 Participants	14 participants n=7 Participants	18 participants n=5 Participants	34 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 7 (8 hours postdose)

Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=14 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7 Baseline (Day 1)	4.36 score on a scale Standard Deviation 1.199	—	—	—	—
Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7 Change from Baseline at Day 7 (8 hours postdose)	-0.69 score on a scale Standard Deviation 1.115	—	—	—	—

PRIMARY outcome

Timeframe: Randomization (Day 8, predose) and Day 14 (predose)

Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=4 Participants 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.	Part A: SAGE-217 Capsules n=4 Participants 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14 Randomization (Day 8)	3.33 score on a scale Standard Deviation 0.714	4.13 score on a scale Standard Deviation 1.438	—	—	—
Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14 Change from Randomization at Day 14 (predose)	0.20 score on a scale Standard Deviation 0.271	0.15 score on a scale Standard Deviation 0.191	—	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 15

Population: The Efficacy Population consisted of all participants who completed at least 1 dose of study drug in Part C and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=16 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part C: Change From Baseline in the Accelerometer-based Kinesia Upper Limb Tremor Combined Score at Day 15 Baseline (Day 1)	11.68 score on a scale Standard Deviation 3.822	—	—	—	—
Part C: Change From Baseline in the Accelerometer-based Kinesia Upper Limb Tremor Combined Score at Day 15 Change from Baseline at Day 15	-2.22 score on a scale Standard Deviation 2.956	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 7 (8 hours postdose)

Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given timepoint.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=14 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part A: Change From Baseline in Kinesia Upper Limb Total Score at Day 7 Baseline (Day 1)	10.50 score on a scale Standard Deviation 4.395	—	—	—	—
Part A: Change From Baseline in Kinesia Upper Limb Total Score at Day 7 Change from Baseline at Day 7 (8 hours postdose)	-2.40 score on a scale Standard Deviation 3.395	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 7 (8 hours [hr] postdose [pd])

Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given timepoint.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=14 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 FOPT at Baseline (Day 1)	2.51 score on a scale Standard Deviation 1.749	—	—	—	—
Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 LWBPT at Baseline (Day 1)	3.63 score on a scale Standard Deviation 1.695	—	—	—	—
Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 Change from Baseline in FOPT at Day 7 (8 hr pd)	-0.74 score on a scale Standard Deviation 1.339	—	—	—	—
Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 Change from Baseline in LWBPT at Day 7 (8 hr pd)	-0.97 score on a scale Standard Deviation 1.312	—	—	—	—
Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7 Kinetic tremor at Baseline (Day 1)	4.36 score on a scale Standard Deviation 1.199	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 7 (8 hours postdose)

Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=14 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part A: Change From Baseline in the Tremor Research Group (TRG) Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Total Score at Day 7 Baseline (Day 1)	12.86 score on a scale Standard Deviation 2.373	—	—	—	—
Part A: Change From Baseline in the Tremor Research Group (TRG) Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Total Score at Day 7 Change from Baseline at Day 7	-4.42 score on a scale Standard Deviation 2.964	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 7 (8 hours postdose)

Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=14 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 Change from Baseline in FOPT at Day 7	-1.46 score on a scale Standard Deviation 1.070	—	—	—	—
Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 Kinetic Tremor at Baseline (Day 1)	4.54 score on a scale Standard Deviation 0.720	—	—	—	—
Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 FOPT at Baseline (Day 1)	4.14 score on a scale Standard Deviation 0.989	—	—	—	—
Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 LWBPT at Baseline (Day 1)	4.18 score on a scale Standard Deviation 0.932	—	—	—	—
Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 Change from Baseline in LWBPT at Day 7	-1.31 score on a scale Standard Deviation 1.011	—	—	—	—
Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7 Change from Baseline in Kinetic Tremor at Day 7	-1.65 score on a scale Standard Deviation 1.179	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 7 (predose)

Population: Efficacy population (Part A; capsules) included all participants who received at least 1 dose of SAGE-217 capsule formulation in Part A and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=14 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 AS at Baseline (Day 1)	4.8 score on a scale Standard Deviation 1.37	—	—	—	—
Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 Change from Baseline in AS at Day 7	-1.0 score on a scale Standard Deviation 1.29	—	—	—	—
Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 Handwriting at Baseline (Day 1)	2.3 score on a scale Standard Deviation 1.07	—	—	—	—
Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 DAT at Baseline (Day 1)	4.46 score on a scale Standard Deviation 0.692	—	—	—	—
Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 Change from Baseline in DAT at Day 7	-0.96 score on a scale Standard Deviation 0.967	—	—	—	—
Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7 Change from Baseline in Handwriting at Day 7	-0.4 score on a scale Standard Deviation 0.77	—	—	—	—

SECONDARY outcome

Timeframe: Randomization (Day 8, predose) and Day 14 (predose)

Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=4 Participants 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.	Part A: SAGE-217 Capsules n=4 Participants 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14 Randomization (Day 8)	7.33 score on a scale Standard Deviation 2.373	9.13 score on a scale Standard Deviation 7.236	—	—	—
Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14 Change from Randomization at Day 14 (predose)	0.93 score on a scale Standard Deviation 2.380	0.55 score on a scale Standard Deviation 0.520	—	—	—

SECONDARY outcome

Timeframe: Randomization (Day 8, predose) and Day 14 (predose)

Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=4 Participants 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.	Part A: SAGE-217 Capsules n=4 Participants 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 FOPT at Randomization (Day 8)	1.60 score on a scale Standard Deviation 1.098	1.85 score on a scale Standard Deviation 2.983	—	—	—
Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 Change from Randomization in FOPT at Day 14	0.03 score on a scale Standard Deviation 0.580	0.38 score on a scale Standard Deviation 0.591	—	—	—
Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 LWBPT at Randomization (Day 8)	2.40 score on a scale Standard Deviation 0.876	3.15 score on a scale Standard Deviation 3.032	—	—	—
Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14 Change from Randomization in LWBPT at Day 14	0.70 score on a scale Standard Deviation 1.553	0.03 score on a scale Standard Deviation 0.263	—	—	—

SECONDARY outcome

Timeframe: Randomization (Day 8, predose) and Day 14 (predose)

Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=4 Participants 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.	Part A: SAGE-217 Capsules n=4 Participants 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14 Randomization (Day 8)	7.88 score on a scale Standard Deviation 1.436	7.63 score on a scale Standard Deviation 4.956	—	—	—
Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14 Change from Randomization at Day 14	1.38 score on a scale Standard Deviation 1.109	0.63 score on a scale Standard Deviation 0.250	—	—	—

SECONDARY outcome

Timeframe: Randomization (Day 8, predose) and Day 14 (predose)

Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=4 Participants 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.	Part A: SAGE-217 Capsules n=4 Participants 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 FOPT at Randomization (Day 8)	2.75 score on a scale Standard Deviation 0.500	2.63 score on a scale Standard Deviation 1.702	—	—	—
Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 Change from Randomization in FOPT at Day 14	0.13 score on a scale Standard Deviation 0.629	0.00 score on a scale Standard Deviation 0.000	—	—	—
Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 LWBPT at Randomization (Day 8)	2.63 score on a scale Standard Deviation 0.479	2.63 score on a scale Standard Deviation 2.056	—	—	—
Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14 Change from Randomization in LWBPT at Day 14	0.38 score on a scale Standard Deviation 0.629	0.25 score on a scale Standard Deviation 0.645	—	—	—

SECONDARY outcome

Timeframe: Randomization (Day 8, predose) and Day 14 (predose)

Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=4 Participants 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.	Part A: SAGE-217 Capsules n=4 Participants 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14 Randomization (Day 8)	2.50 score on a scale Standard Deviation 0.577	2.38 score on a scale Standard Deviation 1.250	—	—	—
Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14 Change from Randomization at Day 14	0.88 score on a scale Standard Deviation 0.479	0.38 score on a scale Standard Deviation 0.479	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 14 (predose)

Population: The Efficacy Population included all participants who completed at least one dose of study drug in Part B and had at least one post-randomization efficacy evaluation.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=4 Participants 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.	Part A: SAGE-217 Capsules n=4 Participants 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 AS at Baseline (Day 1)	5.0 score on a scale Standard Deviation 0.82	5.3 score on a scale Standard Deviation 1.89	—	—	—
Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 Change from Baseline in AS at Day 14	-1.3 score on a scale Standard Deviation 0.96	-1.0 score on a scale Standard Deviation 1.15	—	—	—
Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 Handwriting at Baseline (Day 1)	2.3 score on a scale Standard Deviation 0.96	3.0 score on a scale Standard Deviation 1.41	—	—	—
Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 Change from Baseline in Handwriting at Day 14	-0.5 score on a scale Standard Deviation 1.00	-0.5 score on a scale Standard Deviation 0.58	—	—	—
Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 DAT at Baseline (Day 1)	4.63 score on a scale Standard Deviation 0.629	4.50 score on a scale Standard Deviation 1.000	—	—	—
Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14 Change from Baseline in DAT at Day 14	-1.25 score on a scale Standard Deviation 0.866	-1.38 score on a scale Standard Deviation 1.250	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 15

Population: The Efficacy Population consisted of all participants who completed at least 1 dose of study drug in the capsule formulation in Part C and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=16 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 FOPT at Baseline (Day 1)	2.98 score on a scale Standard Deviation 1.626	—	—	—	—
Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 Change from Baseline in FOPT at Day 15	-0.53 score on a scale Standard Deviation 1.156	—	—	—	—
Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 LWBPT at Baseline (Day 1)	4.41 score on a scale Standard Deviation 1.548	—	—	—	—
Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 Change from Baseline in LWBPT at Day 15	-0.93 score on a scale Standard Deviation 1.497	—	—	—	—
Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 Kinetic tremor at Baseline (Day 1)	4.28 score on a scale Standard Deviation 1.275	—	—	—	—
Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15 Change from Baseline in Kinetic tremor at Day 15	-0.51 score on a scale Standard Deviation 1.229	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 15

Population: The Efficacy Population consisted of all participants who completed at least 1 dose of study drug in the capsule formulation in Part C and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=17 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part C: Change From Baseline in the TETRAS Upper Limb Total Score at Day 15 Baseline (Day 1)	12.82 score on a scale Standard Deviation 1.952	—	—	—	—
Part C: Change From Baseline in the TETRAS Upper Limb Total Score at Day 15 Change from Baseline at Day 15	-1.60 score on a scale Standard Deviation 2.436	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 15

Population: The Efficacy Population consisted of all participants who completed at least 1 dose of study drug in the capsule formulation in Part C and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=17 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 FOPT at Baseline (Day 1)	3.79 score on a scale Standard Deviation 0.867	—	—	—	—
Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 Change from Baseline in FOPT at Day 15	-0.13 score on a scale Standard Deviation 1.060	—	—	—	—
Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 LWBPT at Baseline (Day 1)	4.47 score on a scale Standard Deviation 0.695	—	—	—	—
Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 Change from Baseline in LWBPT at Day 15	-0.80 score on a scale Standard Deviation 0.902	—	—	—	—
Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 Kinetic tremor at Baseline (Day 1)	4.56 score on a scale Standard Deviation 0.726	—	—	—	—
Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15 Change from Baseline in Kinetic tremor at Day 15	-0.67 score on a scale Standard Deviation 0.838	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 15

Population: The Efficacy Population consisted of all participants who completed at least 1 dose of study drug in the capsule formulation in Part C and had at least 1 postdose efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=17 Participants 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.	Part A: SAGE-217 Capsules 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.	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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 AS at Baseline (Day 1)	4.5 score on a scale Standard Deviation 1.97	—	—	—	—
Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 Change from Baseline in AS at Day 15	-0.6 score on a scale Standard Deviation 1.55	—	—	—	—
Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 Handwriting at Baseline (Day 1)	2.4 score on a scale Standard Deviation 1.06	—	—	—	—
Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 Change from Baseline in Handwriting at Day 15	-0.5 score on a scale Standard Deviation 0.74	—	—	—	—
Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 DAT at Baseline (Day 1)	4.25 score on a scale Standard Deviation 0.640	—	—	—	—
Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15 Change from Baseline in DAT at Day 15	-0.23 score on a scale Standard Deviation 0.594	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study drug through 14 days after the last dose (Up to 28 days)

Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B).

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=2 Participants 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.	Part A: SAGE-217 Capsules n=14 Participants 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.	Part B: Placebo n=4 Participants 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.	Part B: SAGE-217 Capsules n=4 Participants 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.	Part C: SAGE-217 Capsules n=18 Participants 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.
Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) At Least One TEAE	2 Participants	7 Participants	0 Participants	1 Participants	10 Participants
Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE) SAE	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and post-baseline (up to 28 days)

Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B).

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=2 Participants 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.	Part A: SAGE-217 Capsules n=14 Participants 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.	Part B: Placebo n=4 Participants 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.	Part B: SAGE-217 Capsules n=4 Participants 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.	Part C: SAGE-217 Capsules n=18 Participants 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.
Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score Wish to be Dead (baseline)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score Wish to be Dead (PB)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score Non-Specific Active Suicidal Thoughts (baseline)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score Non-Specific Active Suicidal Thoughts (PB)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B).

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

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=2 Participants 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.	Part A: SAGE-217 Capsules n=14 Participants 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.	Part B: Placebo n=4 Participants 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.	Part B: SAGE-217 Capsules n=4 Participants 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.	Part C: SAGE-217 Capsules n=18 Participants 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.
Number of Participants With Clinically Significant Vital Signs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B).

Laboratory parameters included hematology, blood chemistry, and urinalysis.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=2 Participants 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.	Part A: SAGE-217 Capsules n=14 Participants 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.	Part B: Placebo n=4 Participants 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.	Part B: SAGE-217 Capsules n=4 Participants 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.	Part C: SAGE-217 Capsules n=18 Participants 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.
Number of Participants With Clinically Significant Laboratory Parameters	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B).

A 12-lead ECG was performed.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=2 Participants 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.	Part A: SAGE-217 Capsules n=14 Participants 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.	Part B: Placebo n=4 Participants 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.	Part B: SAGE-217 Capsules n=4 Participants 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.	Part C: SAGE-217 Capsules n=18 Participants 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.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Values	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 7 (predose) for Part A, Day 14 (predose) for Part B

Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B). Number analyzed is the number of participants with data available for analysis at the given time point. SSS was not evaluated in Part C.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=14 Participants 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.	Part A: SAGE-217 Capsules n=4 Participants 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.	Part B: Placebo n=4 Participants 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.	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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS) Change from Baseline at Day 7 or 14	-0.2 score on a scale Standard Deviation 1.42	-0.5 score on a scale Standard Deviation 0.58	-0.5 score on a scale Standard Deviation 0.58	—	—
Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS) Baseline (Day 1)	2.1 score on a scale Standard Deviation 1.41	1.5 score on a scale Standard Deviation 0.58	2.3 score on a scale Standard Deviation 1.26	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 7 (predose) for Part A, Day 14 (predose) for Part B and Day 15 for Part C

Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B). Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=14 Participants 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.	Part A: SAGE-217 Capsules n=4 Participants 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.	Part B: Placebo n=4 Participants 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.	Part B: SAGE-217 Capsules n=18 Participants 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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score Alertness: Baseline (Day 1)	18.737 log(units on a scale) Standard Deviation 3.8640	18.345 log(units on a scale) Standard Deviation 3.2388	21.308 log(units on a scale) Standard Deviation 2.7694	18.1248 log(units on a scale) Standard Deviation 4.62487	—
Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score Alertness: CFB at Day 7, 14 or 15	-0.148 log(units on a scale) Standard Deviation 6.4794	-2.857 log(units on a scale) Standard Deviation 1.6712	-1.038 log(units on a scale) Standard Deviation 4.6404	1.3095 log(units on a scale) Standard Deviation 5.87702	—
Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score Contentedness: Baseline (Day 1)	10.281 log(units on a scale) Standard Deviation 2.7813	11.284 log(units on a scale) Standard Deviation 0.2150	12.545 log(units on a scale) Standard Deviation 1.7398	9.8911 log(units on a scale) Standard Deviation 3.53165	—
Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score Contentedness: CFB at Day 7, 14 or 15	-0.121 log(units on a scale) Standard Deviation 3.1249	-1.896 log(units on a scale) Standard Deviation 2.2236	-0.471 log(units on a scale) Standard Deviation 2.5222	0.0881 log(units on a scale) Standard Deviation 3.16922	—
Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score Calmness: Baseline (Day 1)	4.589 log(units on a scale) Standard Deviation 1.2740	5.446 log(units on a scale) Standard Deviation 0.7720	5.344 log(units on a scale) Standard Deviation 0.7802	5.6157 log(units on a scale) Standard Deviation 0.89826	—
Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score Calmness: CFB at Day 7, 14 or 15	0.304 log(units on a scale) Standard Deviation 1.4579	-0.613 log(units on a scale) Standard Deviation 0.4106	-0.601 log(units on a scale) Standard Deviation 1.4341	-0.5116 log(units on a scale) Standard Deviation 1.23403	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 7 (2 hours postdose) for Part A, Day 14 (2 hours postdose) for Part B and Day 15 for Part C

Population: The Safety Population consisted of all participants who were administered at least 1 dose of open-label study drug (Parts A and C) or double-blind study drug (Part B). Number analyzed is the number of participants with data available for analysis at the given time point.

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.

Outcome measures

Measure	Part A: SAGE-217 Oral Solution n=14 Participants 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.	Part A: SAGE-217 Capsules n=4 Participants 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.	Part B: Placebo n=4 Participants 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.	Part B: SAGE-217 Capsules n=18 Participants 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.	Part C: SAGE-217 Capsules Participants received a 10-mg dose of SAGE-217 administered with food in the evening on Day 1, 20 mg with food in the evening on Day 2, and 30 mg with food in the evening on Day 3. From Day 4 through 14 participants received a total 40-mg daily dose with food in the evening.
Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score Q1: Day 7, 14 or 15	54.8 units on a scale Standard Deviation 27.56	22.5 units on a scale Standard Deviation 18.84	33.0 units on a scale Standard Deviation 28.23	27.9 units on a scale Standard Deviation 24.57	—
Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score Q2: Day 7, 14 or 15	21.4 units on a scale Standard Deviation 22.56	18.0 units on a scale Standard Deviation 21.65	24.5 units on a scale Standard Deviation 21.44	13.3 units on a scale Standard Deviation 19.72	—
Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score Q3: Day 7, 14 or 15	47.5 units on a scale Standard Deviation 30.63	12.0 units on a scale Standard Deviation 7.83	46.3 units on a scale Standard Deviation 24.85	35.2 units on a scale Standard Deviation 37.04	—
Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score Q4: Day 7, 14 or 15	30.0 units on a scale Standard Deviation 19.65	33.5 units on a scale Standard Deviation 32.25	33.0 units on a scale Standard Deviation 17.44	38.3 units on a scale Standard Deviation 32.48	—
Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score Q5: Day 7, 14 or 15	34.5 units on a scale Standard Deviation 26.13	17.8 units on a scale Standard Deviation 18.61	23.0 units on a scale Standard Deviation 20.12	34.6 units on a scale Standard Deviation 31.11	—

Adverse Events

Part A: SAGE-217 Oral Solution

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: SAGE-217 Capsules

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Part B: Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part B: SAGE-217 Capsules

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part C: SAGE-217 Capsules

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part A: SAGE-217 Oral Solution n=2 participants at risk 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.	Part A: SAGE-217 Capsules n=14 participants at risk 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.	Part B: Placebo n=4 participants at risk 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.	Part B: SAGE-217 Capsules n=4 participants at risk 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.	Part C: SAGE-217 Capsules n=18 participants at risk 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.
Psychiatric disorders Confusional state	50.0% 1/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).

Other adverse events

Measure	Part A: SAGE-217 Oral Solution n=2 participants at risk 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.	Part A: SAGE-217 Capsules n=14 participants at risk 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.	Part B: Placebo n=4 participants at risk 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.	Part B: SAGE-217 Capsules n=4 participants at risk 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.	Part C: SAGE-217 Capsules n=18 participants at risk 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.
Nervous system disorders Dizziness	100.0% 2/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	21.4% 3/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	22.2% 4/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Nervous system disorders Somnolence	50.0% 1/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	28.6% 4/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	27.8% 5/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Nervous system disorders Sedation	50.0% 1/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	14.3% 2/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	11.1% 2/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Nervous system disorders Amnesia	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	7.1% 1/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Nervous system disorders Bradykinesia	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	7.1% 1/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Nervous system disorders Muscle contractions involuntary	50.0% 1/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Nervous system disorders Depressed level of consciousness	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Nervous system disorders Headache	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Psychiatric disorders Somnambulism	50.0% 1/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Psychiatric disorders Anxiety	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Psychiatric disorders Disorientation	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Psychiatric disorders Insomnia	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Psychiatric disorders Nervousness	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Blood and lymphatic system disorders Neutropenia	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	7.1% 1/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Eye disorders Diplopia	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	7.1% 1/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Skin and subcutaneous tissue disorders Skin irritation	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	7.1% 1/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Infections and infestations Conjunctivitis	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Infections and infestations Gastric infection	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
Gastrointestinal disorders Paraesthesia oral	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
General disorders Asthenia	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	5.6% 1/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).
General disorders Gait disturbance	0.00% 0/2 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/14 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	25.0% 1/4 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).	0.00% 0/18 • TEAEs were collected from the first dose of study drug through 14 days after the last dose (up to 28 days). 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).

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: clinicaltrials@biogen.com

Results disclosure agreements

• Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
• Publication restrictions are in place

Restriction type: OTHER