Trial Outcomes & Findings for A Study to Evaluate SAGE-217 in Participants With Parkinson's Disease (NCT NCT03000569)

NCT ID: NCT03000569

Last Updated: 2023-11-29

Results Overview

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 29 participants
• Primary outcome timeframe: Day 1 to Day 14
• Results posted on: 2023-11-29

Participant Flow

Participants were enrolled at 9 sites in the United States and took part in the study which ran from 30 November 2016 to 11 September 2017.

Participant milestones

Measure	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217 Participants on a stable morning dose of levodopa (including carbidopa-levodopa) as antiparkinsonian agent(s) from Days 1 to 3, stopped levodopa and received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. Stable doses of other antiparkinsonian agents and dose reductions in SAGE-217 were allowed between Days 1 to 7. Participants resumed stable morning dose of levodopa from Days 8 to 14.	Part B: Antiparkinsonian Agent(s) + SAGE-217 Participants on a stable dose of antiparkinsonian agent(s) received SAGE-217, up to 30 mg per day, capsules, for Days 1 to 7 in the evening with food.
Overall Study STARTED	15	14
Overall Study COMPLETED	14	14
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217 Participants on a stable morning dose of levodopa (including carbidopa-levodopa) as antiparkinsonian agent(s) from Days 1 to 3, stopped levodopa and received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. Stable doses of other antiparkinsonian agents and dose reductions in SAGE-217 were allowed between Days 1 to 7. Participants resumed stable morning dose of levodopa from Days 8 to 14.	Part B: Antiparkinsonian Agent(s) + SAGE-217 Participants on a stable dose of antiparkinsonian agent(s) received SAGE-217, up to 30 mg per day, capsules, for Days 1 to 7 in the evening with food.
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

A Study to Evaluate SAGE-217 in Participants With Parkinson's Disease

Baseline characteristics by cohort

Measure	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217 n=15 Participants Participants on a stable morning dose of levodopa (including carbidopa-levodopa) as antiparkinsonian agent(s) from Days 1 to 3, stopped levodopa and received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. Stable doses of other antiparkinsonian agents and dose reductions in SAGE-217 were allowed between Days 1 to 7. Participants resumed stable morning dose of levodopa from Days 8 to 14.	Part B: Antiparkinsonian Agent(s) + SAGE-217 n=14 Participants Participants on a stable dose of antiparkinsonian agent(s) received SAGE-217, up to 30 mg per day, capsules, for Days 1 to 7 in the evening with food.	Total n=29 Participants Total of all reporting groups
Age, Continuous	63.9 years STANDARD_DEVIATION 6.59 • n=5 Participants	65.1 years STANDARD_DEVIATION 7.76 • n=7 Participants	64.5 years STANDARD_DEVIATION 7.17 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Overall number of participants analyzed = Number of participants in the safety population that remained in the study during each period.

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. A TEAE was as an AE that occurred after the first administration of study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 n=14 Participants Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up n=15 Participants Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) - Part A	26.7 percentage of participants	100 percentage of participants	13.3 percentage of participants

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Overall number of participants analyzed = Number of participants in the safety population that remained in the study during each period.

Severity was assessed according to the following scale: mild (awareness of sign or symptom, but easily tolerated); moderate (discomfort sufficient to cause interference with normal activities); severe (incapacitating, with an inability to perform normal activities). The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 n=14 Participants Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up n=15 Participants Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
Percentage of Participants With TEAEs, Graded by Severity - Part A Mild	20.0 percentage of participants	0 percentage of participants	6.7 percentage of participants
Percentage of Participants With TEAEs, Graded by Severity - Part A Moderate	6.7 percentage of participants	85.7 percentage of participants	6.7 percentage of participants
Percentage of Participants With TEAEs, Graded by Severity - Part A Severe	0 percentage of participants	14.3 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
Change From Baseline (CFB) in Basophils - Part A Baseline	0.06 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.051	—	—
Change From Baseline (CFB) in Basophils - Part A CFB at Day 4 (SAGE-217)	-0.02 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.043	—	—
Change From Baseline (CFB) in Basophils - Part A CFB at Day 6 (SAGE-217)	-0.01 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.036	—	—
Change From Baseline (CFB) in Basophils - Part A CFB at Day 8 (Follow-up)	0.02 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.038	—	—
Change From Baseline (CFB) in Basophils - Part A CFB at Day 14 (Follow-up)	-0.02 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.041	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as International System (SI) unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Basophils to Leukocytes Ratio [Percentage (%)] - Part A Baseline	0.8 percentage Standard Deviation 0.41	—	—
CFB in Basophils to Leukocytes Ratio [Percentage (%)] - Part A CFB at Day 4 (SAGE-217)	0.1 percentage Standard Deviation 0.66	—	—
CFB in Basophils to Leukocytes Ratio [Percentage (%)] - Part A CFB at Day 6 (SAGE-217)	0.3 percentage Standard Deviation 0.61	—	—
CFB in Basophils to Leukocytes Ratio [Percentage (%)] - Part A CFB at Day 8 (Follow-up)	0.0 percentage Standard Deviation 0.41	—	—
CFB in Basophils to Leukocytes Ratio [Percentage (%)] - Part A CFB at Day 14 (Follow-up)	0.1 percentage Standard Deviation 0.35	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Eosinophils - Part A Baseline	0.17 10^9 cells/L Standard Deviation 0.098	—	—
CFB in Eosinophils - Part A CFB at Day 4 (SAGE-217)	0.07 10^9 cells/L Standard Deviation 0.083	—	—
CFB in Eosinophils - Part A CFB at Day 6 (SAGE-217)	0.04 10^9 cells/L Standard Deviation 0.051	—	—
CFB in Eosinophils - Part A CFB at Day 8 (Follow-up)	0.02 10^9 cells/L Standard Deviation 0.073	—	—
CFB in Eosinophils - Part A CFB at Day 14 (Follow-up)	0.00 10^9 cells/L Standard Deviation 0.053	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Eosinophils to Leukocytes Ratio (%) - Part A Baseline	2.9 percentage Standard Deviation 1.58	—	—
CFB in Eosinophils to Leukocytes Ratio (%) - Part A CFB at Day 4 (SAGE-217)	0.7 percentage Standard Deviation 1.59	—	—
CFB in Eosinophils to Leukocytes Ratio (%) - Part A CFB at Day 6 (SAGE-217)	0.3 percentage Standard Deviation 0.83	—	—
CFB in Eosinophils to Leukocytes Ratio (%) - Part A CFB at Day 8 (Follow-up)	0.0 percentage Standard Deviation 0.82	—	—
CFB in Eosinophils to Leukocytes Ratio (%) - Part A CFB at Day 14 (Follow-up)	-0.3 percentage Standard Deviation 1.11	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Erythrocytes - Part A Baseline	4.63 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.475	—	—
CFB in Erythrocytes - Part A CFB at Day 4 (SAGE-217)	0.01 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.266	—	—
CFB in Erythrocytes - Part A CFB at Day 6 (SAGE-217)	0.04 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.224	—	—
CFB in Erythrocytes - Part A CFB at Day 8 (Follow-up)	0.02 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.265	—	—
CFB in Erythrocytes - Part A CFB at Day 14 (Follow-up)	-0.09 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.226	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Hematocrit - Part A Baseline	0.434 liters per liter (L/L) Standard Deviation 0.0444	—	—
CFB in Hematocrit - Part A CFB at Day 4 (SAGE-217)	0.003 liters per liter (L/L) Standard Deviation 0.0264	—	—
CFB in Hematocrit - Part A CFB at Day 6 (SAGE-217)	0.004 liters per liter (L/L) Standard Deviation 0.0247	—	—
CFB in Hematocrit - Part A CFB at Day 8 (Follow-up)	-0.002 liters per liter (L/L) Standard Deviation 0.0285	—	—
CFB in Hematocrit - Part A CFB at Day 14 (Follow-up)	-0.013 liters per liter (L/L) Standard Deviation 0.0222	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Hemoglobin - Part A Baseline	142.0 grams per liter (g/L) Standard Deviation 13.87	—	—
CFB in Hemoglobin - Part A CFB at Day 4 (SAGE-217)	0.1 grams per liter (g/L) Standard Deviation 7.55	—	—
CFB in Hemoglobin - Part A CFB at Day 6 (SAGE-217)	1.7 grams per liter (g/L) Standard Deviation 7.25	—	—
CFB in Hemoglobin - Part A CFB at Day 8 (Follow-up)	1.2 grams per liter (g/L) Standard Deviation 8.14	—	—
CFB in Hemoglobin - Part A CFB at Day 14 (Follow-up)	-1.9 grams per liter (g/L) Standard Deviation 5.82	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Leukocytes - Part A Baseline	6.04 10^9 cells/L Standard Deviation 1.139	—	—
CFB in Leukocytes - Part A CFB at Day 4 (SAGE-217)	-0.24 10^9 cells/L Standard Deviation 1.085	—	—
CFB in Leukocytes - Part A CFB at Day 6 (SAGE-217)	0.15 10^9 cells/L Standard Deviation 0.536	—	—
CFB in Leukocytes - Part A CFB at Day 8 (Follow-up)	-0.09 10^9 cells/L Standard Deviation 0.874	—	—
CFB in Leukocytes - Part A CFB at Day 14 (Follow-up)	0.30 10^9 cells/L Standard Deviation 0.941	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Lymphocytes - Part A Baseline	1.70 10^9 cells/L Standard Deviation 0.318	—	—
CFB in Lymphocytes - Part A CFB at Day 4 (SAGE-217)	-0.02 10^9 cells/L Standard Deviation 0.289	—	—
CFB in Lymphocytes - Part A CFB at Day 6 (SAGE-217)	0.07 10^9 cells/L Standard Deviation 0.352	—	—
CFB in Lymphocytes - Part A CFB at Day 8 (Follow-up)	0.02 10^9 cells/L Standard Deviation 0.286	—	—
CFB in Lymphocytes - Part A CFB at Day 14 (Follow-up)	-0.17 10^9 cells/L Standard Deviation 0.183	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Lymphocytes to Leukocytes Ratio (%) - Part A Baseline	28.3 percentage Standard Deviation 4.68	—	—
CFB in Lymphocytes to Leukocytes Ratio (%) - Part A CFB at Day 4 (SAGE-217)	1.0 percentage Standard Deviation 4.72	—	—
CFB in Lymphocytes to Leukocytes Ratio (%) - Part A CFB at Day 6 (SAGE-217)	1.0 percentage Standard Deviation 5.55	—	—
CFB in Lymphocytes to Leukocytes Ratio (%) - Part A CFB at Day 8 (Follow-up)	0.9 percentage Standard Deviation 4.87	—	—
CFB in Lymphocytes to Leukocytes Ratio (%) - Part A CFB at Day 14 (Follow-up)	-3.9 percentage Standard Deviation 4.22	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Monocytes - Part A Baseline	0.36 10^9 cells/L Standard Deviation 0.112	—	—
CFB in Monocytes - Part A CFB at Day 4 (SAGE-217)	0.02 10^9 cells/L Standard Deviation 0.125	—	—
CFB in Monocytes - Part A CFB at Day 6 (SAGE-217)	0.06 10^9 cells/L Standard Deviation 0.076	—	—
CFB in Monocytes - Part A CFB at Day 8 (Follow-up)	0.02 10^9 cells/L Standard Deviation 0.101	—	—
CFB in Monocytes - Part A CFB at Day 14 (Follow-up)	0.05 10^9 cells/L Standard Deviation 0.064	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Monocytes to Leukocytes Ratio (%) - Part A Baseline	6.1 percentage Standard Deviation 1.06	—	—
CFB in Monocytes to Leukocytes Ratio (%) - Part A CFB at Day 4 (SAGE-217)	0.2 percentage Standard Deviation 1.48	—	—
CFB in Monocytes to Leukocytes Ratio (%) - Part A CFB at Day 6 (SAGE-217)	0.6 percentage Standard Deviation 1.45	—	—
CFB in Monocytes to Leukocytes Ratio (%) - Part A CFB at Day 8 (Follow-up)	0.5 percentage Standard Deviation 1.33	—	—
CFB in Monocytes to Leukocytes Ratio (%) - Part A CFB at Day 14 (Follow-up)	0.3 percentage Standard Deviation 1.22	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Neutrophils- Part A Baseline	3.79 10^9 cells/L Standard Deviation 0.861	—	—
CFB in Neutrophils- Part A CFB at Day 4 (SAGE-217)	-0.27 10^9 cells/L Standard Deviation 0.848	—	—
CFB in Neutrophils- Part A CFB at Day 6 (SAGE-217)	-0.03 10^9 cells/L Standard Deviation 0.599	—	—
CFB in Neutrophils- Part A CFB at Day 8 (Follow-up)	-0.17 10^9 cells/L Standard Deviation 0.680	—	—
CFB in Neutrophils- Part A CFB at Day 14 (Follow-up)	0.44 10^9 cells/L Standard Deviation 0.861	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Neutrophils to Leukocytes Ratio (%) - Part A Baseline	62.5 percentage Standard Deviation 4.26	—	—
CFB in Neutrophils to Leukocytes Ratio (%) - Part A CFB at Day 4 (SAGE-217)	-2.4 percentage Standard Deviation 4.94	—	—
CFB in Neutrophils to Leukocytes Ratio (%) - Part A CFB at Day 6 (SAGE-217)	-2.4 percentage Standard Deviation 5.58	—	—
CFB in Neutrophils to Leukocytes Ratio (%) - Part A CFB at Day 8 (Follow-up)	-2.2 percentage Standard Deviation 4.86	—	—
CFB in Neutrophils to Leukocytes Ratio (%) - Part A CFB at Day 14 (Follow-up)	3.6 percentage Standard Deviation 4.64	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Platelets - Part A Baseline	218.9 10^9 cells/L Standard Deviation 62.00	—	—
CFB in Platelets - Part A CFB at Day 4 (SAGE-217)	6.6 10^9 cells/L Standard Deviation 27.07	—	—
CFB in Platelets - Part A CFB at Day 6 (SAGE-217)	6.8 10^9 cells/L Standard Deviation 33.01	—	—
CFB in Platelets - Part A CFB at Day 8 (Follow-up)	7.8 10^9 cells/L Standard Deviation 21.29	—	—
CFB in Platelets - Part A CFB at Day 14 (Follow-up)	11.5 10^9 cells/L Standard Deviation 36.42	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Reticulocytes - Part A Baseline	64.6 10^9 cells/L Standard Deviation 20.36	—	—
CFB in Reticulocytes - Part A CFB at Day 4 (SAGE-217)	-0.3 10^9 cells/L Standard Deviation 17.87	—	—
CFB in Reticulocytes - Part A CFB at Day 6 (SAGE-217)	0.3 10^9 cells/L Standard Deviation 19.21	—	—
CFB in Reticulocytes - Part A CFB at Day 8 (Follow-up)	0.2 10^9 cells/L Standard Deviation 20.18	—	—
CFB in Reticulocytes - Part A CFB at Day 14 (Follow-up)	0.3 10^9 cells/L Standard Deviation 14.10	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Reticulocytes to Erythrocytes Ratio (%) - Part A Baseline	1.41 percentage Standard Deviation 0.442	—	—
CFB in Reticulocytes to Erythrocytes Ratio (%) - Part A CFB at Day 4 (SAGE-217)	0.00 percentage Standard Deviation 0.349	—	—
CFB in Reticulocytes to Erythrocytes Ratio (%) - Part A CFB at Day 6 (SAGE-217)	-0.03 percentage Standard Deviation 0.409	—	—
CFB in Reticulocytes to Erythrocytes Ratio (%) - Part A CFB at Day 8 (Follow-up)	0.00 percentage Standard Deviation 0.424	—	—
CFB in Reticulocytes to Erythrocytes Ratio (%) - Part A CFB at Day 14 (Follow-up)	0.03 percentage Standard Deviation 0.315	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio and prothrombin time. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=13 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Activated Partial Thromboplastin Time - Part A Baseline	24.80 seconds (sec) Interval 22.9 to 27.4	—	—
CFB in Activated Partial Thromboplastin Time - Part A CFB at Day 4 (SAGE-217)	0.20 seconds (sec) Interval -1.5 to 4.0	—	—
CFB in Activated Partial Thromboplastin Time - Part A CFB at Day 6 (SAGE-217)	-0.25 seconds (sec) Interval -4.8 to 2.4	—	—
CFB in Activated Partial Thromboplastin Time - Part A CFB at Day 8 (Follow-up)	-0.10 seconds (sec) Interval -1.6 to 1.4	—	—
CFB in Activated Partial Thromboplastin Time - Part A CFB at Day 14 (Follow-up)	-1.10 seconds (sec) Interval -2.1 to 4.7	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio and prothrombin time. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=13 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Prothrombin International Normalized Ratio - Part A Baseline	1.04 ratio Standard Deviation 0.065	—	—
CFB in Prothrombin International Normalized Ratio - Part A CFB at Day 4 (SAGE-217)	0.01 ratio Standard Deviation 0.108	—	—
CFB in Prothrombin International Normalized Ratio - Part A CFB at Day 6 (SAGE-217)	-0.03 ratio Standard Deviation 0.065	—	—
CFB in Prothrombin International Normalized Ratio - Part A CFB at Day 8 (Follow-up)	0.05 ratio Standard Deviation 0.243	—	—
CFB in Prothrombin International Normalized Ratio - Part A CFB at Day 14 (Follow-up)	0.01 ratio Standard Deviation 0.155	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio and prothrombin time. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=13 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Prothrombin Time - Part A Baseline	10.70 sec Interval 10.2 to 12.4	—	—
CFB in Prothrombin Time - Part A CFB at Day 4 (SAGE-217)	0.00 sec Interval -0.6 to 2.2	—	—
CFB in Prothrombin Time - Part A CFB at Day 6 (SAGE-217)	0.00 sec Interval -1.2 to 0.4	—	—
CFB in Prothrombin Time - Part A CFB at Day 8 (Follow-up)	0.10 sec Interval -0.7 to 7.5	—	—
CFB in Prothrombin Time - Part A CFB at Day 14 (Follow-up)	-0.10 sec Interval -1.2 to 4.7	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Alanine Aminotransferase - Part A Baseline	15.8 units per liter (U/L) Standard Deviation 8.12	—	—
CFB in Alanine Aminotransferase - Part A CFB at Day 4 (SAGE-217)	15.3 units per liter (U/L) Standard Deviation 11.61	—	—
CFB in Alanine Aminotransferase - Part A CFB at Day 6 (SAGE-217)	13.9 units per liter (U/L) Standard Deviation 11.87	—	—
CFB in Alanine Aminotransferase - Part A CFB at Day 8 (Follow-up)	7.2 units per liter (U/L) Standard Deviation 13.64	—	—
CFB in Alanine Aminotransferase - Part A CFB at Day 14 (Follow-up)	2.3 units per liter (U/L) Standard Deviation 9.24	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Albumin - Part A Baseline	43.2 g/L Standard Deviation 1.70	—	—
CFB in Albumin - Part A CFB at Day 4 (SAGE-217)	-1.2 g/L Standard Deviation 1.81	—	—
CFB in Albumin - Part A CFB at Day 6 (SAGE-217)	-0.4 g/L Standard Deviation 2.59	—	—
CFB in Albumin - Part A CFB at Day 8 (Follow-up)	-0.1 g/L Standard Deviation 2.21	—	—
CFB in Albumin - Part A CFB at Day 14 (Follow-up)	-0.3 g/L Standard Deviation 2.35	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Alkaline Phosphatase - Part A Baseline	80.6 U/L Standard Deviation 14.17	—	—
CFB in Alkaline Phosphatase - Part A CFB at Day 4 (SAGE-217)	-1.7 U/L Standard Deviation 9.34	—	—
CFB in Alkaline Phosphatase - Part A CFB at Day 6 (SAGE-217)	-2.4 U/L Standard Deviation 4.52	—	—
CFB in Alkaline Phosphatase - Part A CFB at Day 8 (Follow-up)	-0.5 U/L Standard Deviation 4.78	—	—
CFB in Alkaline Phosphatase - Part A CFB at Day 14 (Follow-up)	0.0 U/L Standard Deviation 8.06	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aspartate Aminotransferase - Part A Baseline	23.2 U/L Standard Deviation 7.24	—	—
CFB in Aspartate Aminotransferase - Part A CFB at Day 4 (SAGE-217)	-0.4 U/L Standard Deviation 6.15	—	—
CFB in Aspartate Aminotransferase - Part A CFB at Day 6 (SAGE-217)	-2.4 U/L Standard Deviation 4.93	—	—
CFB in Aspartate Aminotransferase - Part A CFB at Day 8 (Follow-up)	-1.0 U/L Standard Deviation 5.25	—	—
CFB in Aspartate Aminotransferase - Part A CFB at Day 14 (Follow-up)	1.8 U/L Standard Deviation 5.16	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Bicarbonate - Part A Baseline	22.4 millimoles per liter (mmol/L) Standard Deviation 2.50	—	—
CFB in Bicarbonate - Part A CFB at Day 4 (SAGE-217)	-0.9 millimoles per liter (mmol/L) Standard Deviation 2.27	—	—
CFB in Bicarbonate - Part A CFB at Day 6 (SAGE-217)	0.3 millimoles per liter (mmol/L) Standard Deviation 2.23	—	—
CFB in Bicarbonate - Part A CFB at Day 8 (Follow-up)	-0.1 millimoles per liter (mmol/L) Standard Deviation 2.41	—	—
CFB in Bicarbonate - Part A CFB at Day 14 (Follow-up)	0.7 millimoles per liter (mmol/L) Standard Deviation 2.26	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Bilirubin - Part A Baseline	6.082 micromoles per liter (umol/L) Standard Deviation 3.8041	—	—
CFB in Bilirubin - Part A CFB at Day 4 (SAGE-217)	-0.029 micromoles per liter (umol/L) Standard Deviation 3.4758	—	—
CFB in Bilirubin - Part A CFB at Day 6 (SAGE-217)	0.949 micromoles per liter (umol/L) Standard Deviation 3.8554	—	—
CFB in Bilirubin - Part A CFB at Day 8 (Follow-up)	1.545 micromoles per liter (umol/L) Standard Deviation 3.5965	—	—
CFB in Bilirubin - Part A CFB at Day 14 (Follow-up)	0.543 micromoles per liter (umol/L) Standard Deviation 3.7159	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Calcium - Part A Baseline	2.342 mmol/L Standard Deviation 0.0588	—	—
CFB in Calcium - Part A CFB at Day 4 (SAGE-217)	-0.030 mmol/L Standard Deviation 0.0734	—	—
CFB in Calcium - Part A CFB at Day 6 (SAGE-217)	0.007 mmol/L Standard Deviation 0.0779	—	—
CFB in Calcium - Part A CFB at Day 8 (Follow-up)	-0.014 mmol/L Standard Deviation 0.0711	—	—
CFB in Calcium - Part A CFB at Day 14 (Follow-up)	-0.015 mmol/L Standard Deviation 0.0842	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Chloride - Part A Baseline	100.1 mmol/L Standard Deviation 2.33	—	—
CFB in Chloride - Part A CFB at Day 4 (SAGE-217)	1.6 mmol/L Standard Deviation 1.91	—	—
CFB in Chloride - Part A CFB at Day 6 (SAGE-217)	1.1 mmol/L Standard Deviation 2.30	—	—
CFB in Chloride - Part A CFB at Day 8 (Follow-up)	0.5 mmol/L Standard Deviation 2.41	—	—
CFB in Chloride - Part A CFB at Day 14 (Follow-up)	0.3 mmol/L Standard Deviation 1.83	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Creatinine - Part A Baseline	73.254 umol/L Standard Deviation 17.7960	—	—
CFB in Creatinine - Part A CFB at Day 4 (SAGE-217)	2.399 umol/L Standard Deviation 8.6574	—	—
CFB in Creatinine - Part A CFB at Day 6 (SAGE-217)	4.104 umol/L Standard Deviation 9.4424	—	—
CFB in Creatinine - Part A CFB at Day 8 (Follow-up)	4.420 umol/L Standard Deviation 10.9866	—	—
CFB in Creatinine - Part A CFB at Day 14 (Follow-up)	0.118 umol/L Standard Deviation 4.6761	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Lipase - Part A Baseline	34.5 U/L Standard Deviation 10.16	—	—
CFB in Lipase - Part A CFB at Day 4 (SAGE-217)	16.6 U/L Standard Deviation 22.15	—	—
CFB in Lipase - Part A CFB at Day 6 (SAGE-217)	35.1 U/L Standard Deviation 77.58	—	—
CFB in Lipase - Part A CFB at Day 8 (Follow-up)	73.3 U/L Standard Deviation 222.02	—	—
CFB in Lipase - Part A CFB at Day 14 (Follow-up)	-1.6 U/L Standard Deviation 7.67	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Magnesium - Part A Baseline	0.861 mmol/L Standard Deviation 0.0686	—	—
CFB in Magnesium - Part A CFB at Day 4 (SAGE-217)	-0.012 mmol/L Standard Deviation 0.0409	—	—
CFB in Magnesium - Part A CFB at Day 6 (SAGE-217)	0.000 mmol/L Standard Deviation 0.0457	—	—
CFB in Magnesium - Part A CFB at Day 8 (Follow-up)	0.015 mmol/L Standard Deviation 0.0617	—	—
CFB in Magnesium - Part A CFB at Day 14 (Follow-up)	0.016 mmol/L Standard Deviation 0.0618	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Phosphate - Part A Baseline	1.098 mmol/L Standard Deviation 0.1189	—	—
CFB in Phosphate - Part A CFB at Day 4 (SAGE-217)	0.035 mmol/L Standard Deviation 0.1413	—	—
CFB in Phosphate - Part A CFB at Day 6 (SAGE-217)	0.076 mmol/L Standard Deviation 0.1645	—	—
CFB in Phosphate - Part A CFB at Day 8 (Follow-up)	0.083 mmol/L Standard Deviation 0.1513	—	—
CFB in Phosphate - Part A CFB at Day 14 (Follow-up)	-0.034 mmol/L Standard Deviation 0.1698	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Potassium - Part A Baseline	4.53 mmol/L Standard Deviation 0.326	—	—
CFB in Potassium - Part A CFB at Day 4 (SAGE-217)	-0.14 mmol/L Standard Deviation 0.323	—	—
CFB in Potassium - Part A CFB at Day 6 (SAGE-217)	-0.08 mmol/L Standard Deviation 0.309	—	—
CFB in Potassium - Part A CFB at Day 8 (Follow-up)	-0.15 mmol/L Standard Deviation 0.350	—	—
CFB in Potassium - Part A CFB at Day 14 (Follow-up)	-0.08 mmol/L Standard Deviation 0.446	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Protein - Part A Baseline	69.4 g/L Standard Deviation 3.07	—	—
CFB in Protein - Part A CFB at Day 4 (SAGE-217)	-2.3 g/L Standard Deviation 4.12	—	—
CFB in Protein - Part A CFB at Day 6 (SAGE-217)	-1.5 g/L Standard Deviation 3.86	—	—
CFB in Protein - Part A CFB at Day 8 (Follow-up)	-0.4 g/L Standard Deviation 3.65	—	—
CFB in Protein - Part A CFB at Day 14 (Follow-up)	-1.1 g/L Standard Deviation 4.33	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Sodium - Part A Baseline	140.0 mmol/L Standard Deviation 1.73	—	—
CFB in Sodium - Part A CFB at Day 4 (SAGE-217)	0.8 mmol/L Standard Deviation 2.15	—	—
CFB in Sodium - Part A CFB at Day 6 (SAGE-217)	1.3 mmol/L Standard Deviation 1.86	—	—
CFB in Sodium - Part A CFB at Day 8 (Follow-up)	0.7 mmol/L Standard Deviation 2.20	—	—
CFB in Sodium - Part A CFB at Day 14 (Follow-up)	0.5 mmol/L Standard Deviation 1.85	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Urate - Part A Baseline	0.337 mmol/L Standard Deviation 0.1000	—	—
CFB in Urate - Part A CFB at Day 4 (SAGE-217)	-0.005 mmol/L Standard Deviation 0.0713	—	—
CFB in Urate - Part A CFB at Day 6 (SAGE-217)	0.010 mmol/L Standard Deviation 0.0804	—	—
CFB in Urate - Part A CFB at Day 8 (Follow-up)	0.014 mmol/L Standard Deviation 0.0394	—	—
CFB in Urate - Part A CFB at Day 14 (Follow-up)	-0.014 mmol/L Standard Deviation 0.0649	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Urea Nitrogen - Part A Baseline	5.831 mmol/L Standard Deviation 1.3672	—	—
CFB in Urea Nitrogen - Part A CFB at Day 4 (SAGE-217)	0.587 mmol/L Standard Deviation 1.4925	—	—
CFB in Urea Nitrogen - Part A CFB at Day 6 (SAGE-217)	0.816 mmol/L Standard Deviation 1.4715	—	—
CFB in Urea Nitrogen - Part A CFB at Day 8 (Follow-up)	0.663 mmol/L Standard Deviation 1.5521	—	—
CFB in Urea Nitrogen - Part A CFB at Day 14 (Follow-up)	-0.048 mmol/L Standard Deviation 1.3484	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Urinalysis measures included specific gravity and potential of hydrogen (pH). Baseline is the last measurement taken before the first dose of study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Specific Gravity - Part A Baseline	1.018 ratio Standard Deviation 0.0049	—	—
CFB in Specific Gravity - Part A CFB at Day 4 (SAGE-217)	-0.001 ratio Standard Deviation 0.0062	—	—
CFB in Specific Gravity - Part A CFB at Day 7 (SAGE-217)	0.000 ratio Standard Deviation 0.0039	—	—
CFB in Specific Gravity - Part A CFB at Day 14 (Follow-up)	0.002 ratio Standard Deviation 0.0059	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Urinalysis measures included specific gravity and pH. Baseline is the last measurement taken before the first dose of study drug. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in pH - Part A Baseline	5.87 pH Standard Deviation 0.915	—	—
CFB in pH - Part A CFB at Day 4 (SAGE-217)	0.18 pH Standard Deviation 0.973	—	—
CFB in pH - Part A CFB at Day 7 (SAGE-217)	-0.11 pH Standard Deviation 0.881	—	—
CFB in pH - Part A CFB at Day 14 (Follow-up)	-0.07 pH Standard Deviation 0.884	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Temperature - Part A Baseline	36.61 degrees Celsius (degrees C) Standard Deviation 0.228	—	—
CFB in Temperature - Part A CFB at Day 1 (L/C): 1 Hour Postdose	-0.04 degrees Celsius (degrees C) Standard Deviation 0.180	—	—
CFB in Temperature - Part A CFB at Day 1 (L/C): 2 Hours Postdose	-0.01 degrees Celsius (degrees C) Standard Deviation 0.205	—	—
CFB in Temperature - Part A CFB at Day 1 (L/C): 3 Hours Postdose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.236	—	—
CFB in Temperature - Part A CFB at Day 1 (L/C): 4 Hours Postdose	-0.08 degrees Celsius (degrees C) Standard Deviation 0.227	—	—
CFB in Temperature - Part A CFB at Day 1 (L/C): 6 Hours Postdose	-0.06 degrees Celsius (degrees C) Standard Deviation 0.285	—	—
CFB in Temperature - Part A CFB at Day 1 (L/C): 8 Hours Postdose	0.00 degrees Celsius (degrees C) Standard Deviation 0.235	—	—
CFB in Temperature - Part A CFB at Day 1 (L/C): 12 Hours Postdose	0.08 degrees Celsius (degrees C) Standard Deviation 0.412	—	—
CFB in Temperature - Part A CFB at Day 1 (L/C): 14 Hours Postdose	0.00 degrees Celsius (degrees C) Standard Deviation 0.319	—	—
CFB in Temperature - Part A CFB at Day 1 (L/C): 16 Hours Postdose	-0.01 degrees Celsius (degrees C) Standard Deviation 0.296	—	—
CFB in Temperature - Part A CFB at Day 2 (L/C): Predose	-0.06 degrees Celsius (degrees C) Standard Deviation 0.346	—	—
CFB in Temperature - Part A CFB at Day 2 (L/C): 1 Hour Postdose	-0.11 degrees Celsius (degrees C) Standard Deviation 0.316	—	—
CFB in Temperature - Part A CFB at Day 2 (L/C): 2 Hours Postdose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.348	—	—
CFB in Temperature - Part A CFB at Day 2 (L/C): 3 Hours Postdose	-0.04 degrees Celsius (degrees C) Standard Deviation 0.323	—	—
CFB in Temperature - Part A CFB at Day 2 (L/C): 4 Hours Postdose	-0.07 degrees Celsius (degrees C) Standard Deviation 0.279	—	—
CFB in Temperature - Part A CFB at Day 2 (L/C): 6 Hours Postdose	-0.11 degrees Celsius (degrees C) Standard Deviation 0.274	—	—
CFB in Temperature - Part A CFB at Day 2 (L/C): 8 Hours Postdose	-0.02 degrees Celsius (degrees C) Standard Deviation 0.283	—	—
CFB in Temperature - Part A CFB at Day 2 (L/C): 12 Hours Postdose	0.06 degrees Celsius (degrees C) Standard Deviation 0.380	—	—
CFB in Temperature - Part A CFB at Day 2 (L/C): 14 Hours Postdose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.380	—	—
CFB in Temperature - Part A CFB at Day 2 (L/C): 16 Hours Postdose	-0.06 degrees Celsius (degrees C) Standard Deviation 0.365	—	—
CFB in Temperature - Part A CFB at Day 3 (L/C): Predose	0.09 degrees Celsius (degrees C) Standard Deviation 0.409	—	—
CFB in Temperature - Part A CFB at Day 3 (L/C): 1 Hour Postdose	-0.09 degrees Celsius (degrees C) Standard Deviation 0.305	—	—
CFB in Temperature - Part A CFB at Day 3 (L/C): 2 Hours Postdose	-0.10 degrees Celsius (degrees C) Standard Deviation 0.277	—	—
CFB in Temperature - Part A CFB at Day 3 (L/C): 3 Hours Postdose	-0.10 degrees Celsius (degrees C) Standard Deviation 0.272	—	—
CFB in Temperature - Part A CFB at Day 3 (L/C): 4 Hours Postdose	-0.03 degrees Celsius (degrees C) Standard Deviation 0.331	—	—
CFB in Temperature - Part A CFB at Day 3 (L/C): 6 Hours Postdose	-0.06 degrees Celsius (degrees C) Standard Deviation 0.363	—	—
CFB in Temperature - Part A CFB at Day 3 (L/C): 8 Hours Postdose	-0.04 degrees Celsius (degrees C) Standard Deviation 0.276	—	—
CFB in Temperature - Part A CFB at Day 3 (L/C): 12 Hours Postdose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.422	—	—
CFB in Temperature - Part A CFB at Day 3 (L/C): 14 Hours Postdose	-0.01 degrees Celsius (degrees C) Standard Deviation 0.372	—	—
CFB in Temperature - Part A CFB at Day 3 (L/C): 16 Hours Postdose	0.04 degrees Celsius (degrees C) Standard Deviation 0.176	—	—
CFB in Temperature - Part A CFB at Day 4 (SAGE-217): Predose	0.02 degrees Celsius (degrees C) Standard Deviation 0.208	—	—
CFB in Temperature - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	0.01 degrees Celsius (degrees C) Standard Deviation 0.175	—	—
CFB in Temperature - Part A CFB at Day 4 (SAGE-217): 2 Hours Postdose	0.08 degrees Celsius (degrees C) Standard Deviation 0.387	—	—
CFB in Temperature - Part A CFB at Day 4 (SAGE-217): 3 Hours Postdose	-0.07 degrees Celsius (degrees C) Standard Deviation 0.236	—	—
CFB in Temperature - Part A CFB at Day 4 (SAGE-217): 4 Hours Postdose	-0.11 degrees Celsius (degrees C) Standard Deviation 0.236	—	—
CFB in Temperature - Part A CFB at Day 4 (SAGE-217): 6 Hours Postdose	0.03 degrees Celsius (degrees C) Standard Deviation 0.230	—	—
CFB in Temperature - Part A CFB at Day 4 (SAGE-217): 8 Hours Postdose	-0.03 degrees Celsius (degrees C) Standard Deviation 0.336	—	—
CFB in Temperature - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	-0.02 degrees Celsius (degrees C) Standard Deviation 0.333	—	—
CFB in Temperature - Part A CFB at Day 4 (SAGE-217): 14 Hours Postdose	0.12 degrees Celsius (degrees C) Standard Deviation 0.185	—	—
CFB in Temperature - Part A CFB at Day 4 (SAGE-217): 16 Hours Postdose	0.07 degrees Celsius (degrees C) Standard Deviation 0.233	—	—
CFB in Temperature - Part A CFB at Day 5 (SAGE-217): Predose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.187	—	—
CFB in Temperature - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	-0.04 degrees Celsius (degrees C) Standard Deviation 0.287	—	—
CFB in Temperature - Part A CFB at Day 5 (SAGE-217): 2 Hours Postdose	-0.16 degrees Celsius (degrees C) Standard Deviation 0.360	—	—
CFB in Temperature - Part A CFB at Day 5 (SAGE-217): 3 Hours Postdose	-0.17 degrees Celsius (degrees C) Standard Deviation 0.272	—	—
CFB in Temperature - Part A CFB at Day 5 (SAGE-217): 4 Hours Postdose	-0.02 degrees Celsius (degrees C) Standard Deviation 0.449	—	—
CFB in Temperature - Part A CFB at Day 5 (SAGE-217): 6 Hours Postdose	-0.16 degrees Celsius (degrees C) Standard Deviation 0.310	—	—
CFB in Temperature - Part A CFB at Day 5 (SAGE-217): 8 Hours Postdose	-0.07 degrees Celsius (degrees C) Standard Deviation 0.421	—	—
CFB in Temperature - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	-0.09 degrees Celsius (degrees C) Standard Deviation 0.400	—	—
CFB in Temperature - Part A CFB at Day 5 (SAGE-217): 14 Hours Postdose	-0.07 degrees Celsius (degrees C) Standard Deviation 0.273	—	—
CFB in Temperature - Part A CFB at Day 5 (SAGE-217): 16 Hours Postdose	-0.02 degrees Celsius (degrees C) Standard Deviation 0.383	—	—
CFB in Temperature - Part A CFB at Day 6 (SAGE-217): Predose	-0.04 degrees Celsius (degrees C) Standard Deviation 0.359	—	—
CFB in Temperature - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	0.02 degrees Celsius (degrees C) Standard Deviation 0.306	—	—
CFB in Temperature - Part A CFB at Day 6 (SAGE-217): 2 Hours Postdose	-0.08 degrees Celsius (degrees C) Standard Deviation 0.322	—	—
CFB in Temperature - Part A CFB at Day 6 (SAGE-217): 3 Hours Postdose	-0.13 degrees Celsius (degrees C) Standard Deviation 0.322	—	—
CFB in Temperature - Part A CFB at Day 6 (SAGE-217): 4 Hours Postdose	-0.12 degrees Celsius (degrees C) Standard Deviation 0.358	—	—
CFB in Temperature - Part A CFB at Day 6 (SAGE-217): 6 Hours Postdose	-0.09 degrees Celsius (degrees C) Standard Deviation 0.260	—	—
CFB in Temperature - Part A CFB at Day 6 (SAGE-217): 8 Hours Postdose	-0.08 degrees Celsius (degrees C) Standard Deviation 0.329	—	—
CFB in Temperature - Part A CFB at Day 6 (SAGE-217): 12 Hours Postdose	-0.10 degrees Celsius (degrees C) Standard Deviation 0.697	—	—
CFB in Temperature - Part A CFB at Day 6 (SAGE-217): 14 Hours Postdose	-0.04 degrees Celsius (degrees C) Standard Deviation 0.434	—	—
CFB in Temperature - Part A CFB at Day 6 (SAGE-217): 16 Hours Postdose	0.06 degrees Celsius (degrees C) Standard Deviation 0.434	—	—
CFB in Temperature - Part A CFB at Day 7 (SAGE-217): Predose	-0.13 degrees Celsius (degrees C) Standard Deviation 0.302	—	—
CFB in Temperature - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	-0.16 degrees Celsius (degrees C) Standard Deviation 0.282	—	—
CFB in Temperature - Part A CFB at Day 7 (SAGE-217): 2 Hours Postdose	-0.16 degrees Celsius (degrees C) Standard Deviation 0.407	—	—
CFB in Temperature - Part A CFB at Day 7 (SAGE-217): 3 Hours Postdose	-0.16 degrees Celsius (degrees C) Standard Deviation 0.310	—	—
CFB in Temperature - Part A CFB at Day 7 (SAGE-217): 4 Hours Postdose	-0.11 degrees Celsius (degrees C) Standard Deviation 0.332	—	—
CFB in Temperature - Part A CFB at Day 7 (SAGE-217): 6 Hours Postdose	-0.13 degrees Celsius (degrees C) Standard Deviation 0.252	—	—
CFB in Temperature - Part A CFB at Day 7 (SAGE-217): 8 Hours Postdose	0.02 degrees Celsius (degrees C) Standard Deviation 0.208	—	—
CFB in Temperature - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	0.06 degrees Celsius (degrees C) Standard Deviation 0.145	—	—
CFB in Temperature - Part A CFB at Day 7 (SAGE-217): 14 Hours Postdose	-0.01 degrees Celsius (degrees C) Standard Deviation 0.235	—	—
CFB in Temperature - Part A CFB at Day 7 (SAGE-217): 16 Hours Postdose	-0.03 degrees Celsius (degrees C) Standard Deviation 0.363	—	—
CFB in Temperature - Part A CFB at Day 8 (Follow-up)	0.4 degrees Celsius (degrees C) Standard Deviation 0.224	—	—
CFB in Temperature - Part A CFB at Day 14 (Follow-up)	0.07 degrees Celsius (degrees C) Standard Deviation 0.301	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Heart Rate - Part A CFB at Day 7 (SAGE-217): 8 Hours Postdose	4.8 beats per minute (beats/min) Standard Deviation 4.66	—	—
CFB in Heart Rate - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	9.5 beats per minute (beats/min) Standard Deviation 9.82	—	—
CFB in Heart Rate - Part A CFB at Day 7 (SAGE-217): 14 Hours Postdose	6.7 beats per minute (beats/min) Standard Deviation 9.27	—	—
CFB in Heart Rate - Part A CFB at Day 7 (SAGE-217): 16 Hours Postdose	5.6 beats per minute (beats/min) Standard Deviation 7.93	—	—
CFB in Heart Rate - Part A CFB at Day 8 (Follow-up)	1.8 beats per minute (beats/min) Standard Deviation 6.52	—	—
CFB in Heart Rate - Part A CFB at Day 14 (Follow-up)	4.1 beats per minute (beats/min) Standard Deviation 8.29	—	—
CFB in Heart Rate - Part A CFB at Day 6 (SAGE-217): 6 Hours Postdose	5.1 beats per minute (beats/min) Standard Deviation 10.07	—	—
CFB in Heart Rate - Part A CFB at Day 6 (SAGE-217): 8 Hours Postdose	4.6 beats per minute (beats/min) Standard Deviation 11.00	—	—
CFB in Heart Rate - Part A CFB at Day 6 (SAGE-217): 12 Hours Postdose	4.8 beats per minute (beats/min) Standard Deviation 10.87	—	—
CFB in Heart Rate - Part A CFB at Day 6 (SAGE-217): 14 Hours Postdose	5.2 beats per minute (beats/min) Standard Deviation 9.51	—	—
CFB in Heart Rate - Part A CFB at Day 6 (SAGE-217): 16 Hours Postdose	5.4 beats per minute (beats/min) Standard Deviation 10.87	—	—
CFB in Heart Rate - Part A CFB at Day 7 (SAGE-217): Predose	8.4 beats per minute (beats/min) Standard Deviation 11.06	—	—
CFB in Heart Rate - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	6.0 beats per minute (beats/min) Standard Deviation 8.29	—	—
CFB in Heart Rate - Part A CFB at Day 7 (SAGE-217): 2 Hours Postdose	5.3 beats per minute (beats/min) Standard Deviation 6.49	—	—
CFB in Heart Rate - Part A CFB at Day 7 (SAGE-217): 3 Hours Postdose	3.9 beats per minute (beats/min) Standard Deviation 12.50	—	—
CFB in Heart Rate - Part A CFB at Day 7 (SAGE-217): 4 Hours Postdose	4.4 beats per minute (beats/min) Standard Deviation 7.77	—	—
CFB in Heart Rate - Part A CFB at Day 7 (SAGE-217): 6 Hours Postdose	6.0 beats per minute (beats/min) Standard Deviation 8.46	—	—
CFB in Heart Rate - Part A Baseline	66.6 beats per minute (beats/min) Standard Deviation 11.83	—	—
CFB in Heart Rate - Part A CFB at Day 1 (L/C): 1 Hour Postdose	2.1 beats per minute (beats/min) Standard Deviation 5.87	—	—
CFB in Heart Rate - Part A CFB at Day 1 (L/C): 2 Hours Postdose	1.3 beats per minute (beats/min) Standard Deviation 6.76	—	—
CFB in Heart Rate - Part A CFB at Day 1 (L/C): 3 Hours Postdose	-0.5 beats per minute (beats/min) Standard Deviation 5.87	—	—
CFB in Heart Rate - Part A CFB at Day 1 (L/C): 4 Hours Postdose	-1.3 beats per minute (beats/min) Standard Deviation 6.63	—	—
CFB in Heart Rate - Part A CFB at Day 1 (L/C): 6 Hours Postdose	0.8 beats per minute (beats/min) Standard Deviation 7.75	—	—
CFB in Heart Rate - Part A CFB at Day 1 (L/C): 8 Hours Postdose	0.4 beats per minute (beats/min) Standard Deviation 7.55	—	—
CFB in Heart Rate - Part A CFB at Day 1 (L/C): 12 Hours Postdose	5.5 beats per minute (beats/min) Standard Deviation 6.86	—	—
CFB in Heart Rate - Part A CFB at Day 1 (L/C): 14 Hours Postdose	0.5 beats per minute (beats/min) Standard Deviation 7.18	—	—
CFB in Heart Rate - Part A CFB at Day 1 (L/C): 16 Hours Postdose	1.4 beats per minute (beats/min) Standard Deviation 5.03	—	—
CFB in Heart Rate - Part A CFB at Day 2 (L/C): Predose	-0.2 beats per minute (beats/min) Standard Deviation 6.80	—	—
CFB in Heart Rate - Part A CFB at Day 2 (L/C): 1 Hour Postdose	2.1 beats per minute (beats/min) Standard Deviation 7.37	—	—
CFB in Heart Rate - Part A CFB at Day 2 (L/C): 2 Hours Postdose	1.9 beats per minute (beats/min) Standard Deviation 8.10	—	—
CFB in Heart Rate - Part A CFB at Day 2 (L/C): 3 Hours Postdose	-0.3 beats per minute (beats/min) Standard Deviation 10.71	—	—
CFB in Heart Rate - Part A CFB at Day 2 (L/C): 4 Hours Postdose	-0.9 beats per minute (beats/min) Standard Deviation 5.23	—	—
CFB in Heart Rate - Part A CFB at Day 2 (L/C): 6 Hours Postdose	2.1 beats per minute (beats/min) Standard Deviation 7.08	—	—
CFB in Heart Rate - Part A CFB at Day 2 (L/C): 8 Hours Postdos	3.8 beats per minute (beats/min) Standard Deviation 7.81	—	—
CFB in Heart Rate - Part A CFB at Day 2 (L/C): 12 Hours Postdose	3.9 beats per minute (beats/min) Standard Deviation 8.38	—	—
CFB in Heart Rate - Part A CFB at Day 2 (L/C): 14 Hours Postdose	1.6 beats per minute (beats/min) Standard Deviation 7.29	—	—
CFB in Heart Rate - Part A CFB at Day 2 (L/C): 16 Hours Postdose	1.2 beats per minute (beats/min) Standard Deviation 7.29	—	—
CFB in Heart Rate - Part A CFB at Day 3 (L/C): Predose	-0.7 beats per minute (beats/min) Standard Deviation 9.29	—	—
CFB in Heart Rate - Part A CFB at Day 3 (L/C): 1 Hour Postdose	4.7 beats per minute (beats/min) Standard Deviation 6.67	—	—
CFB in Heart Rate - Part A CFB at Day 3 (L/C): 2 Hours Postdose	2.4 beats per minute (beats/min) Standard Deviation 9.46	—	—
CFB in Heart Rate - Part A CFB at Day 3 (L/C): 3 Hours Postdose	1.2 beats per minute (beats/min) Standard Deviation 7.20	—	—
CFB in Heart Rate - Part A CFB at Day 3 (L/C): 4 Hours Postdose	0.6 beats per minute (beats/min) Standard Deviation 6.30	—	—
CFB in Heart Rate - Part A CFB at Day 3 (L/C): 6 Hours Postdose	1.7 beats per minute (beats/min) Standard Deviation 7.33	—	—
CFB in Heart Rate - Part A CFB at Day 3 (L/C): 8 Hours Postdose	5.9 beats per minute (beats/min) Standard Deviation 5.43	—	—
CFB in Heart Rate - Part A CFB at Day 3 (L/C): 12 Hours Postdose	2.6 beats per minute (beats/min) Standard Deviation 9.72	—	—
CFB in Heart Rate - Part A CFB at Day 3 (L/C): 14 Hours Postdose	3.6 beats per minute (beats/min) Standard Deviation 8.63	—	—
CFB in Heart Rate - Part A CFB at Day 3 (L/C): 16 Hours Postdose	3.9 beats per minute (beats/min) Standard Deviation 7.08	—	—
CFB in Heart Rate - Part A CFB at Day 4 (SAGE-217): Predose	1.4 beats per minute (beats/min) Standard Deviation 5.21	—	—
CFB in Heart Rate - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	3.7 beats per minute (beats/min) Standard Deviation 6.43	—	—
CFB in Heart Rate - Part A CFB at Day 4 (SAGE-217): 2 Hours Postdose	1.6 beats per minute (beats/min) Standard Deviation 8.97	—	—
CFB in Heart Rate - Part A CFB at Day 4 (SAGE-217): 3 Hours Postdose	3.4 beats per minute (beats/min) Standard Deviation 10.38	—	—
CFB in Heart Rate - Part A CFB at Day 4 (SAGE-217): 4 Hours Postdose	0.6 beats per minute (beats/min) Standard Deviation 6.27	—	—
CFB in Heart Rate - Part A CFB at Day 4 (SAGE-217): 6 Hours Postdose	2.7 beats per minute (beats/min) Standard Deviation 8.72	—	—
CFB in Heart Rate - Part A CFB at Day 4 (SAGE-217): 8 Hours Postdose	2.1 beats per minute (beats/min) Standard Deviation 7.97	—	—
CFB in Heart Rate - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	5.1 beats per minute (beats/min) Standard Deviation 9.70	—	—
CFB in Heart Rate - Part A CFB at Day 4 (SAGE-217): 14 Hours Postdose	5.2 beats per minute (beats/min) Standard Deviation 6.64	—	—
CFB in Heart Rate - Part A CFB at Day 4 (SAGE-217): 16 Hours Postdose	4.6 beats per minute (beats/min) Standard Deviation 7.37	—	—
CFB in Heart Rate - Part A CFB at Day 5 (SAGE-217): Predose	1.5 beats per minute (beats/min) Standard Deviation 8.25	—	—
CFB in Heart Rate - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	3.8 beats per minute (beats/min) Standard Deviation 6.99	—	—
CFB in Heart Rate - Part A CFB at Day 5 (SAGE-217): 2 Hours Postdose	4.4 beats per minute (beats/min) Standard Deviation 9.06	—	—
CFB in Heart Rate - Part A CFB at Day 5 (SAGE-217): 3 Hours Postdose	3.4 beats per minute (beats/min) Standard Deviation 8.18	—	—
CFB in Heart Rate - Part A CFB at Day 5 (SAGE-217): 4 Hours Postdose	1.3 beats per minute (beats/min) Standard Deviation 11.03	—	—
CFB in Heart Rate - Part A CFB at Day 5 (SAGE-217): 6 Hours Postdose	7.6 beats per minute (beats/min) Standard Deviation 11.24	—	—
CFB in Heart Rate - Part A CFB at Day 5 (SAGE-217): 8 Hours Postdose	4.2 beats per minute (beats/min) Standard Deviation 9.50	—	—
CFB in Heart Rate - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	8.4 beats per minute (beats/min) Standard Deviation 9.51	—	—
CFB in Heart Rate - Part A CFB at Day 5 (SAGE-217): 14 Hours Postdose	6.6 beats per minute (beats/min) Standard Deviation 7.98	—	—
CFB in Heart Rate - Part A CFB at Day 5 (SAGE-217): 16 Hours Postdose	3.7 beats per minute (beats/min) Standard Deviation 9.34	—	—
CFB in Heart Rate - Part A CFB at Day 6 (SAGE-217): Predose	4.6 beats per minute (beats/min) Standard Deviation 7.58	—	—
CFB in Heart Rate - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	4.3 beats per minute (beats/min) Standard Deviation 6.53	—	—
CFB in Heart Rate - Part A CFB at Day 6 (SAGE-217): 2 Hours Postdose	2.9 beats per minute (beats/min) Standard Deviation 7.86	—	—
CFB in Heart Rate - Part A CFB at Day 6 (SAGE-217): 3 Hours Postdose	4.2 beats per minute (beats/min) Standard Deviation 7.51	—	—
CFB in Heart Rate - Part A CFB at Day 6 (SAGE-217): 4 Hours Postdose	3.2 beats per minute (beats/min) Standard Deviation 10.09	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Respiratory Rate - Part A Baseline	15.9 breaths per minute (breaths/min) Standard Deviation 1.92	—	—
CFB in Respiratory Rate - Part A CFB at Day 1 (L/C): 1 Hour Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.46	—	—
CFB in Respiratory Rate - Part A CFB at Day 1 (L/C): 2 Hours Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.92	—	—
CFB in Respiratory Rate - Part A CFB at Day 1 (L/C): 3 Hours Postdose	0.0 breaths per minute (breaths/min) Standard Deviation 1.69	—	—
CFB in Respiratory Rate - Part A CFB at Day 1 (L/C): 4 Hours Postdose	0.2 breaths per minute (breaths/min) Standard Deviation 1.93	—	—
CFB in Respiratory Rate - Part A CFB at Day 1 (L/C): 6 Hours Postdose	0.0 breaths per minute (breaths/min) Standard Deviation 1.69	—	—
CFB in Respiratory Rate - Part A CFB at Day 1 (L/C): 8 Hours Postdose	1.0 breaths per minute (breaths/min) Standard Deviation 2.08	—	—
CFB in Respiratory Rate - Part A CFB at Day 1 (L/C): 12 Hours Postdose	0.6 breaths per minute (breaths/min) Standard Deviation 1.99	—	—
CFB in Respiratory Rate - Part A CFB at Day 1 (L/C): 14 Hours Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.83	—	—
CFB in Respiratory Rate - Part A CFB at Day 1 (L/C): 16 Hours Postdose	-0.2 breaths per minute (breaths/min) Standard Deviation 2.49	—	—
CFB in Respiratory Rate - Part A CFB at Day 2 (L/C): Predose	-0.1 breaths per minute (breaths/min) Standard Deviation 1.59	—	—
CFB in Respiratory Rate - Part A CFB at Day 2 (L/C): 1 Hour Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.83	—	—
CFB in Respiratory Rate - Part A CFB at Day 2 (L/C): 2 Hours Postdose	0.2 breaths per minute (breaths/min) Standard Deviation 1.48	—	—
CFB in Respiratory Rate - Part A CFB at Day 2 (L/C): 3 Hours Postdose	0.0 breaths per minute (breaths/min) Standard Deviation 1.57	—	—
CFB in Respiratory Rate - Part A CFB at Day 2 (L/C): 4 Hours Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 1.70	—	—
CFB in Respiratory Rate - Part A CFB at Day 2 (L/C): 6 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 2.14	—	—
CFB in Respiratory Rate - Part A CFB at Day 2 (L/C): 8 Hours Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 2.32	—	—
CFB in Respiratory Rate - Part A CFB at Day 2 (L/C): 12 Hours Postdose	0.3 breaths per minute (breaths/min) Standard Deviation 2.61	—	—
CFB in Respiratory Rate - Part A CFB at Day 2 (L/C): 14 Hours Postdose	0.3 breaths per minute (breaths/min) Standard Deviation 2.92	—	—
CFB in Respiratory Rate - Part A CFB at Day 2 (L/C): 16 Hours Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 2.62	—	—
CFB in Respiratory Rate - Part A CFB at Day 3 (L/C): Predose	-0.4 breaths per minute (breaths/min) Standard Deviation 1.99	—	—
CFB in Respiratory Rate - Part A CFB at Day 3 (L/C): 1 Hour Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 1.65	—	—
CFB in Respiratory Rate - Part A CFB at Day 3 (L/C): 2 Hours Postdose	-0.1 breaths per minute (breaths/min) Standard Deviation 2.03	—	—
CFB in Respiratory Rate - Part A CFB at Day 3 (L/C): 3 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 2.13	—	—
CFB in Respiratory Rate - Part A CFB at Day 3 (L/C): 4 Hours Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 2.11	—	—
CFB in Respiratory Rate - Part A CFB at Day 3 (L/C): 6 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 1.87	—	—
CFB in Respiratory Rate - Part A CFB at Day 3 (L/C): 8 Hours Postdose	0.2 breaths per minute (breaths/min) Standard Deviation 2.26	—	—
CFB in Respiratory Rate - Part A CFB at Day 3 (L/C): 12 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 1.65	—	—
CFB in Respiratory Rate - Part A CFB at Day 3 (L/C): 14 Hours Postdose	0.2 breaths per minute (breaths/min) Standard Deviation 1.93	—	—
CFB in Respiratory Rate - Part A CFB at Day 3 (L/C): 16 Hours Postdose	0.0 breaths per minute (breaths/min) Standard Deviation 2.74	—	—
CFB in Respiratory Rate - Part A CFB at Day 4 (SAGE-217): Predose	0.9 breaths per minute (breaths/min) Standard Deviation 1.59	—	—
CFB in Respiratory Rate - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	-0.3 breaths per minute (breaths/min) Standard Deviation 2.69	—	—
CFB in Respiratory Rate - Part A CFB at Day 4 (SAGE-217): 2 Hours Postdose	-0.4 breaths per minute (breaths/min) Standard Deviation 2.79	—	—
CFB in Respiratory Rate - Part A CFB at Day 4 (SAGE-217): 3 Hours Postdose	0.3 breaths per minute (breaths/min) Standard Deviation 2.39	—	—
CFB in Respiratory Rate - Part A CFB at Day 4 (SAGE-217): 4 Hours Postdose	-0.1 breaths per minute (breaths/min) Standard Deviation 1.66	—	—
CFB in Respiratory Rate - Part A CFB at Day 4 (SAGE-217): 6 Hours Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.21	—	—
CFB in Respiratory Rate - Part A CFB at Day 4 (SAGE-217): 8 Hours Postdose	0.7 breaths per minute (breaths/min) Standard Deviation 1.68	—	—
CFB in Respiratory Rate - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	0.9 breaths per minute (breaths/min) Standard Deviation 1.86	—	—
CFB in Respiratory Rate - Part A CFB at Day 4 (SAGE-217): 14 Hours Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 1.70	—	—
CFB in Respiratory Rate - Part A CFB at Day 4 (SAGE-217): 16 Hours Postdose	-0.3 breaths per minute (breaths/min) Standard Deviation 2.02	—	—
CFB in Respiratory Rate - Part A CFB at Day 5 (SAGE-217): Predose	-0.1 breaths per minute (breaths/min) Standard Deviation 1.59	—	—
CFB in Respiratory Rate - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	-0.3 breaths per minute (breaths/min) Standard Deviation 2.20	—	—
CFB in Respiratory Rate - Part A CFB at Day 5 (SAGE-217): 2 Hours Postdose	-0.4 breaths per minute (breaths/min) Standard Deviation 2.34	—	—
CFB in Respiratory Rate - Part A CFB at Day 5 (SAGE-217): 3 Hours Postdose	-0.1 breaths per minute (breaths/min) Standard Deviation 1.77	—	—
CFB in Respiratory Rate - Part A CFB at Day 5 (SAGE-217): 4 Hours Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.86	—	—
CFB in Respiratory Rate - Part A CFB at Day 5 (SAGE-217): 6 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 2.27	—	—
CFB in Respiratory Rate - Part A CFB at Day 5 (SAGE-217): 8 Hours Postdose	1.0 breaths per minute (breaths/min) Standard Deviation 1.92	—	—
CFB in Respiratory Rate - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 1.95	—	—
CFB in Respiratory Rate - Part A CFB at Day 5 (SAGE-217): 14 Hours Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 1.95	—	—
CFB in Respiratory Rate - Part A CFB at Day 5 (SAGE-217): 16 Hours Postdose	0.3 breaths per minute (breaths/min) Standard Deviation 2.05	—	—
CFB in Respiratory Rate - Part A CFB at Day 6 (SAGE-217): Predose	-0.1 breaths per minute (breaths/min) Standard Deviation 1.38	—	—
CFB in Respiratory Rate - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	-0.6 breaths per minute (breaths/min) Standard Deviation 1.65	—	—
CFB in Respiratory Rate - Part A CFB at Day 6 (SAGE-217): 2 Hours Postdose	-0.3 breaths per minute (breaths/min) Standard Deviation 1.38	—	—
CFB in Respiratory Rate - Part A CFB at Day 6 (SAGE-217): 3 Hours Postdose	-0.1 breaths per minute (breaths/min) Standard Deviation 2.18	—	—
CFB in Respiratory Rate - Part A CFB at Day 6 (SAGE-217): 4 Hours Postdose	-0.1 breaths per minute (breaths/min) Standard Deviation 1.79	—	—
CFB in Respiratory Rate - Part A CFB at Day 6 (SAGE-217): 6 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 2.21	—	—
CFB in Respiratory Rate - Part A CFB at Day 6 (SAGE-217): 8 Hours Postdose	1.0 breaths per minute (breaths/min) Standard Deviation 1.92	—	—
CFB in Respiratory Rate - Part A CFB at Day 6 (SAGE-217): 12 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 2.82	—	—
CFB in Respiratory Rate - Part A CFB at Day 6 (SAGE-217): 14 Hours Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 2.10	—	—
CFB in Respiratory Rate - Part A CFB at Day 6 (SAGE-217): 16 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 2.31	—	—
CFB in Respiratory Rate - Part A CFB at Day 7 (SAGE-217): Predose	0.0 breaths per minute (breaths/min) Standard Deviation 1.36	—	—
CFB in Respiratory Rate - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.27	—	—
CFB in Respiratory Rate - Part A CFB at Day 7 (SAGE-217): 2 Hours Postdose	0.9 breaths per minute (breaths/min) Standard Deviation 1.51	—	—
CFB in Respiratory Rate - Part A CFB at Day 7 (SAGE-217): 3 Hours Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.49	—	—
CFB in Respiratory Rate - Part A CFB at Day 7 (SAGE-217): 4 Hours Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.66	—	—
CFB in Respiratory Rate - Part A CFB at Day 7 (SAGE-217): 6 Hours Postdose	0.6 breaths per minute (breaths/min) Standard Deviation 1.65	—	—
CFB in Respiratory Rate - Part A CFB at Day 7 (SAGE-217): 8 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 1.65	—	—
CFB in Respiratory Rate - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	1.4 breaths per minute (breaths/min) Standard Deviation 2.03	—	—
CFB in Respiratory Rate - Part A CFB at Day 7 (SAGE-217): 14 Hours Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 2.31	—	—
CFB in Respiratory Rate - Part A CFB at Day 7 (SAGE-217): 16 Hours Postdose	0.7 breaths per minute (breaths/min) Standard Deviation 2.61	—	—
CFB in Respiratory Rate - Part A CFB at Day 8 (Follow-up)	0.1 breaths per minute (breaths/min) Standard Deviation 1.29	—	—
CFB in Respiratory Rate - Part A CFB at Day 14 (Follow-up)	0.9 breaths per minute (breaths/min) Standard Deviation 1.83	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Supine Systolic Blood Pressure - Part A Baseline	124.5 millimeters of mercury (mmHg) Standard Deviation 11.61	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 1 Hour Postdose	-6.7 millimeters of mercury (mmHg) Standard Deviation 10.81	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 2 Hours Postdose	-7.1 millimeters of mercury (mmHg) Standard Deviation 11.49	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 3 Hours Postdose	-1.5 millimeters of mercury (mmHg) Standard Deviation 10.37	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 4 Hours Postdose	-4.7 millimeters of mercury (mmHg) Standard Deviation 9.44	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 6 Hours Postdose	-4.5 millimeters of mercury (mmHg) Standard Deviation 9.63	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 8 Hours Postdose	2.4 millimeters of mercury (mmHg) Standard Deviation 13.32	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 12 Hours Postdose	3.4 millimeters of mercury (mmHg) Standard Deviation 13.21	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 14 Hours Postdose	-3.0 millimeters of mercury (mmHg) Standard Deviation 12.51	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 16 Hours Postdose	-3.9 millimeters of mercury (mmHg) Standard Deviation 11.99	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 2 (L/C): Predose	-0.4 millimeters of mercury (mmHg) Standard Deviation 11.14	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 1 Hour Postdose	-7.3 millimeters of mercury (mmHg) Standard Deviation 11.59	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 2 Hours Postdose	-4.4 millimeters of mercury (mmHg) Standard Deviation 9.99	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 3 Hours Postdose	-0.8 millimeters of mercury (mmHg) Standard Deviation 10.86	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 4 Hours Postdose	-1.1 millimeters of mercury (mmHg) Standard Deviation 10.43	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 6 Hours Postdose	-1.6 millimeters of mercury (mmHg) Standard Deviation 10.95	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 8 Hours Postdose	3.2 millimeters of mercury (mmHg) Standard Deviation 15.35	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 12 Hours Postdose	5.9 millimeters of mercury (mmHg) Standard Deviation 8.00	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 14 Hours Postdose	3.4 millimeters of mercury (mmHg) Standard Deviation 9.53	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 16 Hours Postdose	0.9 millimeters of mercury (mmHg) Standard Deviation 10.40	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 3 (L/C): Predose	1.2 millimeters of mercury (mmHg) Standard Deviation 8.61	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 1 Hour Postdose	-2.5 millimeters of mercury (mmHg) Standard Deviation 10.30	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 2 Hours Postdose	-7.4 millimeters of mercury (mmHg) Standard Deviation 14.70	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 3 Hours Postdose	-3.1 millimeters of mercury (mmHg) Standard Deviation 12.69	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 4 Hours Postdose	-3.7 millimeters of mercury (mmHg) Standard Deviation 14.12	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 6 Hours Postdose	-3.1 millimeters of mercury (mmHg) Standard Deviation 12.51	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 8 Hours Postdose	-1.3 millimeters of mercury (mmHg) Standard Deviation 12.75	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 12 Hours Postdose	3.3 millimeters of mercury (mmHg) Standard Deviation 13.30	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 14 Hours Postdose	3.6 millimeters of mercury (mmHg) Standard Deviation 16.21	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 16 Hours Postdose	-3.3 millimeters of mercury (mmHg) Standard Deviation 10.73	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): Predose	3.5 millimeters of mercury (mmHg) Standard Deviation 10.17	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	-4.8 millimeters of mercury (mmHg) Standard Deviation 9.75	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 2 Hours Postdose	-6.6 millimeters of mercury (mmHg) Standard Deviation 10.80	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 3 Hours Postdose	2.3 millimeters of mercury (mmHg) Standard Deviation 15.97	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 4 Hours Postdose	-1.6 millimeters of mercury (mmHg) Standard Deviation 8.84	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 6 Hours Postdose	-3.9 millimeters of mercury (mmHg) Standard Deviation 10.46	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 8 Hours Postdose	2.2 millimeters of mercury (mmHg) Standard Deviation 10.94	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	3.1 millimeters of mercury (mmHg) Standard Deviation 9.60	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 14 Hours Postdose	-3.1 millimeters of mercury (mmHg) Standard Deviation 14.15	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 16 Hours Postdose	-2.6 millimeters of mercury (mmHg) Standard Deviation 10.83	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): Predose	0.1 millimeters of mercury (mmHg) Standard Deviation 11.43	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	-8.6 millimeters of mercury (mmHg) Standard Deviation 9.68	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 2 Hours Postdose	-8.1 millimeters of mercury (mmHg) Standard Deviation 11.67	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 3 Hours Postdose	-5.8 millimeters of mercury (mmHg) Standard Deviation 10.14	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 4 Hours Postdose	-0.4 millimeters of mercury (mmHg) Standard Deviation 9.23	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 6 Hours Postdose	-2.9 millimeters of mercury (mmHg) Standard Deviation 11.14	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 8 Hours Postdose	-3.8 millimeters of mercury (mmHg) Standard Deviation 10.15	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	1.3 millimeters of mercury (mmHg) Standard Deviation 11.68	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 14 Hours Postdose	1.7 millimeters of mercury (mmHg) Standard Deviation 15.46	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 16 Hours Postdose	0.6 millimeters of mercury (mmHg) Standard Deviation 14.19	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): Predose	-5.9 millimeters of mercury (mmHg) Standard Deviation 11.67	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	-8.6 millimeters of mercury (mmHg) Standard Deviation 11.95	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 2 Hours Postdose	-3.8 millimeters of mercury (mmHg) Standard Deviation 13.03	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 3 Hours Postdose	-4.1 millimeters of mercury (mmHg) Standard Deviation 15.47	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 4 Hours Postdose	-5.6 millimeters of mercury (mmHg) Standard Deviation 13.00	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 6 Hours Postdose	-4.4 millimeters of mercury (mmHg) Standard Deviation 10.23	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 8 Hours Postdose	-0.1 millimeters of mercury (mmHg) Standard Deviation 12.46	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 12 Hours Postdose	-0.1 millimeters of mercury (mmHg) Standard Deviation 12.41	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 14 Hours Postdose	2.5 millimeters of mercury (mmHg) Standard Deviation 10.39	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 16 Hours Postdose	1.8 millimeters of mercury (mmHg) Standard Deviation 13.45	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): Predose	1.9 millimeters of mercury (mmHg) Standard Deviation 19.64	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	-5.9 millimeters of mercury (mmHg) Standard Deviation 12.93	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 2 Hours Postdose	-5.4 millimeters of mercury (mmHg) Standard Deviation 18.93	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 3 Hours Postdose	-2.8 millimeters of mercury (mmHg) Standard Deviation 13.22	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 4 Hours Postdose	-5.1 millimeters of mercury (mmHg) Standard Deviation 17.35	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 6 Hours Postdose	-3.9 millimeters of mercury (mmHg) Standard Deviation 14.81	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 8 Hours Postdose	-3.1 millimeters of mercury (mmHg) Standard Deviation 10.38	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	2.9 millimeters of mercury (mmHg) Standard Deviation 13.23	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 14 Hours Postdose	-0.6 millimeters of mercury (mmHg) Standard Deviation 14.07	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 16 Hours Postdose	-0.2 millimeters of mercury (mmHg) Standard Deviation 18.75	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 8 (Follow-up)	1.7 millimeters of mercury (mmHg) Standard Deviation 7.79	—	—
CFB in Supine Systolic Blood Pressure - Part A CFB at Day 14 (Follow-up)	2.7 millimeters of mercury (mmHg) Standard Deviation 9.50	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Standing Systolic Blood Pressure - Part A Baseline	124.1 mmHg Standard Deviation 12.38	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 1 Hour Postdose	-3.1 mmHg Standard Deviation 9.98	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 2 Hours Postdose	-4.7 mmHg Standard Deviation 10.00	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 3 Hours Postdose	-2.9 mmHg Standard Deviation 11.45	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 4 Hours Postdose	0.0 mmHg Standard Deviation 11.78	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 6 Hours Postdose	2.7 mmHg Standard Deviation 13.34	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 8 Hours Postdose	4.3 mmHg Standard Deviation 10.22	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 12 Hours Postdose	7.6 mmHg Standard Deviation 17.85	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 14 Hours Postdose	2.9 mmHg Standard Deviation 10.18	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 1 (L/C): 16 Hours Postdose	-2.7 mmHg Standard Deviation 9.51	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 2 (L/C): Predose	1.0 mmHg Standard Deviation 11.09	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 1 Hour Postdose	-2.9 mmHg Standard Deviation 10.57	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 2 Hours Postdose	-3.4 mmHg Standard Deviation 11.56	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 3 Hours Postdose	-5.1 mmHg Standard Deviation 9.86	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 4 Hours Postdose	0.0 mmHg Standard Deviation 10.12	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 6 Hours Postdose	-3.4 mmHg Standard Deviation 8.50	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 8 Hours Postdose	-0.6 mmHg Standard Deviation 10.20	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 12 Hours Postdose	5.6 mmHg Standard Deviation 16.97	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 14 Hours Postdose	2.0 mmHg Standard Deviation 11.08	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 2 (L/C): 16 Hours Postdose	-4.4 mmHg Standard Deviation 10.14	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 3 (L/C): Predose	-1.4 mmHg Standard Deviation 7.84	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 1 Hour Postdose	-4.2 mmHg Standard Deviation 8.17	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 2 Hours Postdose	-4.9 mmHg Standard Deviation 11.83	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 3 Hours Postdose	-4.4 mmHg Standard Deviation 13.07	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 4 Hours Postdose	-6.2 mmHg Standard Deviation 13.13	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 6 Hours Postdose	-3.2 mmHg Standard Deviation 9.35	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 8 Hours Postdose	-3.2 mmHg Standard Deviation 10.83	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 12 Hours Postdose	1.8 mmHg Standard Deviation 14.56	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 14 Hours Postdose	0.0 mmHg Standard Deviation 15.65	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 3 (L/C): 16 Hours Postdose	2.2 mmHg Standard Deviation 11.98	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): Predose	3.3 mmHg Standard Deviation 13.32	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	-1.5 mmHg Standard Deviation 14.74	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 2 Hours Postdose	-4.6 mmHg Standard Deviation 10.60	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 3 Hours Postdose	-0.5 mmHg Standard Deviation 11.77	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 4 Hours Postdose	-5.7 mmHg Standard Deviation 10.04	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 6 Hours Postdose	-2.3 mmHg Standard Deviation 8.50	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 8 Hours Postdose	0.9 mmHg Standard Deviation 9.16	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	3.3 mmHg Standard Deviation 12.72	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 14 Hours Postdose	0.0 mmHg Standard Deviation 10.09	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 16 Hours Postdose	-1.3 mmHg Standard Deviation 10.07	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): Predose	-0.6 mmHg Standard Deviation 9.61	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	-9.8 mmHg Standard Deviation 12.60	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 2 Hours Postdose	-8.3 mmHg Standard Deviation 10.52	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 3 Hours Postdose	-3.8 mmHg Standard Deviation 14.81	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 4 Hours Postdose	-2.4 mmHg Standard Deviation 9.82	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 6 Hours Postdose	-2.1 mmHg Standard Deviation 12.05	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 8 Hours Postdose	-3.3 mmHg Standard Deviation 10.16	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	1.4 mmHg Standard Deviation 12.51	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 14 Hours Postdose	2.3 mmHg Standard Deviation 17.97	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 16 Hours Postdose	0.8 mmHg Standard Deviation 15.37	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): Predose	-3.3 mmHg Standard Deviation 12.00	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	-6.4 mmHg Standard Deviation 10.89	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 2 Hours Postdose	-5.5 mmHg Standard Deviation 9.34	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 3 Hours Postdose	-3.5 mmHg Standard Deviation 10.36	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 4 Hours Postdose	-2.8 mmHg Standard Deviation 8.55	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 6 Hours Postdose	1.6 mmHg Standard Deviation 9.45	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 8 Hours Postdose	-2.7 mmHg Standard Deviation 12.79	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 12 Hours Postdose	-2.9 mmHg Standard Deviation 12.13	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 14 Hours Postdose	2.5 mmHg Standard Deviation 13.57	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 16 Hours Postdose	0.6 mmHg Standard Deviation 19.21	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): Predose	-0.2 mmHg Standard Deviation 12.25	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	-4.0 mmHg Standard Deviation 13.06	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 2 Hours Postdose	-4.7 mmHg Standard Deviation 13.19	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 3 Hours Postdose	-6.0 mmHg Standard Deviation 9.27	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 4 Hours Postdose	-5.9 mmHg Standard Deviation 13.96	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 6 Hours Postdose	-2.4 mmHg Standard Deviation 13.65	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 8 Hours Postdose	2.1 mmHg Standard Deviation 10.80	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	4.6 mmHg Standard Deviation 14.54	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 14 Hours Postdose	3.7 mmHg Standard Deviation 13.23	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 16 Hours Postdose	0.5 mmHg Standard Deviation 11.95	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 8 (Follow-up)	7.6 mmHg Standard Deviation 9.90	—	—
CFB in Standing Systolic Blood Pressure - Part A CFB at Day 14 (Follow-up)	3.6 mmHg Standard Deviation 13.14	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Supine Diastolic Blood Pressure - Part A Baseline	77.3 mmHg Standard Deviation 7.19	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 1 Hour Postdose	-5.3 mmHg Standard Deviation 6.02	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 2 Hours Postdose	-4.7 mmHg Standard Deviation 5.92	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 3 Hours Postdose	-3.2 mmHg Standard Deviation 6.66	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 4 Hours Postdose	-3.1 mmHg Standard Deviation 5.26	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 6 Hours Postdose	-3.9 mmHg Standard Deviation 9.91	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 8 Hours Postdose	-0.4 mmHg Standard Deviation 9.04	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 12 Hours Postdose	-0.1 mmHg Standard Deviation 7.89	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 14 Hours Postdose	-3.6 mmHg Standard Deviation 8.94	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 16 Hours Postdose	-5.0 mmHg Standard Deviation 10.34	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): Predose	0.7 mmHg Standard Deviation 7.10	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 1 Hour Postdose	-4.8 mmHg Standard Deviation 9.49	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 2 Hours Postdose	-3.4 mmHg Standard Deviation 9.90	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 3 Hours Postdose	-2.2 mmHg Standard Deviation 11.37	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 4 Hours Postdose	-2.5 mmHg Standard Deviation 7.78	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 6 Hours Postdose	-1.4 mmHg Standard Deviation 10.09	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 8 Hours Postdose	-1.4 mmHg Standard Deviation 10.47	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 12 Hours Postdose	0.9 mmHg Standard Deviation 7.57	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 14 Hours Postdose	-1.9 mmHg Standard Deviation 8.08	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 16 Hours Postdose	-3.4 mmHg Standard Deviation 7.13	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): Predose	-0.8 mmHg Standard Deviation 7.29	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 1 Hour Postdose	-5.1 mmHg Standard Deviation 8.51	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 2 Hours Postdose	-3.1 mmHg Standard Deviation 8.11	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 3 Hours Postdose	-4.3 mmHg Standard Deviation 9.77	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 4 Hours Postdose	-5.9 mmHg Standard Deviation 13.63	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 6 Hours Postdose	-4.1 mmHg Standard Deviation 8.77	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 8 Hours Postdose	-3.9 mmHg Standard Deviation 9.90	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 12 Hours Postdose	-1.0 mmHg Standard Deviation 8.32	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 14 Hours Postdose	-0.9 mmHg Standard Deviation 7.80	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 16 Hours Postdose	-2.5 mmHg Standard Deviation 8.69	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): Predose	1.8 mmHg Standard Deviation 7.82	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	-1.9 mmHg Standard Deviation 6.72	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 2 Hours Postdose	-3.6 mmHg Standard Deviation 6.48	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 3 Hours Postdose	1.5 mmHg Standard Deviation 8.19	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 4 Hours Postdose	-0.8 mmHg Standard Deviation 8.01	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 6 Hours Postdose	-3.6 mmHg Standard Deviation 8.75	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 8 Hours Postdose	-1.7 mmHg Standard Deviation 7.08	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	0.0 mmHg Standard Deviation 6.93	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 14 Hours Postdose	-3.6 mmHg Standard Deviation 8.84	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 16 Hours Postdose	-4.0 mmHg Standard Deviation 7.05	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): Predose	-2.1 mmHg Standard Deviation 8.43	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	-5.4 mmHg Standard Deviation 7.72	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 2 Hours Postdose	-2.4 mmHg Standard Deviation 6.17	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 3 Hours Postdose	-3.1 mmHg Standard Deviation 6.62	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 4 Hours Postdose	-3.3 mmHg Standard Deviation 6.93	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 6 Hours Postdose	-2.4 mmHg Standard Deviation 8.22	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 8 Hours Postdose	-3.4 mmHg Standard Deviation 7.00	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	-4.0 mmHg Standard Deviation 9.17	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 14 Hours Postdose	-4.3 mmHg Standard Deviation 7.84	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 16 Hours Postdose	-2.2 mmHg Standard Deviation 10.02	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): Predose	-3.6 mmHg Standard Deviation 7.59	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	-3.7 mmHg Standard Deviation 9.72	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 2 Hours Postdose	-2.7 mmHg Standard Deviation 9.31	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 3 Hours Postdose	-1.8 mmHg Standard Deviation 8.99	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 4 Hours Postdose	-1.8 mmHg Standard Deviation 11.37	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 6 Hours Postdose	-3.9 mmHg Standard Deviation 8.09	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 8 Hours Postdose	-1.7 mmHg Standard Deviation 8.06	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 12 Hours Postdose	-1.0 mmHg Standard Deviation 9.17	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 14 Hours Postdose	0.8 mmHg Standard Deviation 7.71	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 16 Hours Postdose	-3.6 mmHg Standard Deviation 10.30	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): Predose	-1.9 mmHg Standard Deviation 6.75	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	-5.1 mmHg Standard Deviation 7.79	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 2 Hours Postdose	-3.5 mmHg Standard Deviation 9.61	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 3 Hours Postdose	-2.7 mmHg Standard Deviation 10.46	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 4 Hours Postdose	-4.5 mmHg Standard Deviation 9.40	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 6 Hours Postdose	-4.8 mmHg Standard Deviation 8.58	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 8 Hours Postdose	-2.2 mmHg Standard Deviation 10.02	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	-1.0 mmHg Standard Deviation 8.58	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 14 Hours Postdose	-3.5 mmHg Standard Deviation 10.65	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 16 Hours Postdose	-4.2 mmHg Standard Deviation 9.66	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 8 (Follow-up)	-3.8 mmHg Standard Deviation 8.05	—	—
CFB in Supine Diastolic Blood Pressure - Part A CFB at Day 14 (Follow-up)	-2.2 mmHg Standard Deviation 7.22	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Standing Diastolic Blood Pressure - Part A Baseline	76.7 mmHg Standard Deviation 10.57	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 1 Hour Postdose	0.4 mmHg Standard Deviation 8.71	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 2 Hours Postdose	-2.9 mmHg Standard Deviation 7.26	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 3 Hours Postdose	0.7 mmHg Standard Deviation 7.92	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 4 Hours Postdose	2.3 mmHg Standard Deviation 5.57	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 6 Hours Postdose	0.9 mmHg Standard Deviation 10.54	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 8 Hours Postdose	3.1 mmHg Standard Deviation 7.16	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 12 Hours Postdose	2.6 mmHg Standard Deviation 7.04	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 14 Hours Postdose	1.3 mmHg Standard Deviation 7.65	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 1 (L/C): 16 Hours Postdose	1.6 mmHg Standard Deviation 7.19	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): Predose	4.0 mmHg Standard Deviation 8.41	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 1 Hour Postdose	1.6 mmHg Standard Deviation 7.89	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 2 Hours Postdose	1.1 mmHg Standard Deviation 12.25	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 3 Hours Postdose	1.1 mmHg Standard Deviation 8.53	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 4 Hours Postdose	3.8 mmHg Standard Deviation 10.08	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 6 Hours Postdose	0.3 mmHg Standard Deviation 12.55	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 8 Hours Postdose	1.6 mmHg Standard Deviation 10.91	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 12 Hours Postdose	4.3 mmHg Standard Deviation 6.80	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 14 Hours Postdose	3.7 mmHg Standard Deviation 5.99	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 2 (L/C): 16 Hours Postdose	0.1 mmHg Standard Deviation 5.34	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): Predose	4.4 mmHg Standard Deviation 7.82	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 1 Hour Postdose	-1.1 mmHg Standard Deviation 9.44	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 2 Hours Postdose	-0.9 mmHg Standard Deviation 6.98	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 3 Hours Postdose	-1.7 mmHg Standard Deviation 12.74	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 4 Hours Postdose	-0.7 mmHg Standard Deviation 11.23	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 6 Hours Postdose	-0.6 mmHg Standard Deviation 9.94	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 8 Hours Postdose	-1.0 mmHg Standard Deviation 11.90	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 12 Hours Postdose	0.6 mmHg Standard Deviation 7.43	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 14 Hours Postdose	1.8 mmHg Standard Deviation 9.57	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 3 (L/C): 16 Hours Postdose	3.8 mmHg Standard Deviation 10.98	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): Predose	4.6 mmHg Standard Deviation 9.11	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	1.8 mmHg Standard Deviation 8.09	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 2 Hours Postdose	2.4 mmHg Standard Deviation 6.86	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 3 Hours Postdose	5.6 mmHg Standard Deviation 7.50	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 4 Hours Postdose	3.7 mmHg Standard Deviation 7.90	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 6 Hours Postdose	0.3 mmHg Standard Deviation 8.17	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 8 Hours Postdose	1.9 mmHg Standard Deviation 7.88	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	4.8 mmHg Standard Deviation 11.13	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 14 Hours Postdose	1.9 mmHg Standard Deviation 10.41	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 4 (SAGE-217): 16 Hours Postdose	2.8 mmHg Standard Deviation 9.24	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): Predose	2.6 mmHg Standard Deviation 5.84	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	-2.5 mmHg Standard Deviation 5.99	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 2 Hours Postdose	-0.8 mmHg Standard Deviation 6.66	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 3 Hours Postdose	3.8 mmHg Standard Deviation 6.44	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 4 Hours Postdose	2.7 mmHg Standard Deviation 6.34	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 6 Hours Postdose	1.6 mmHg Standard Deviation 6.21	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 8 Hours Postdose	0.1 mmHg Standard Deviation 8.02	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	0.2 mmHg Standard Deviation 9.27	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 14 Hours Postdose	0.4 mmHg Standard Deviation 9.18	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 5 (SAGE-217): 16 Hours Postdose	0.8 mmHg Standard Deviation 9.71	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): Predose	-0.4 mmHg Standard Deviation 8.56	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	0.9 mmHg Standard Deviation 7.45	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 2 Hours Postdose	0.8 mmHg Standard Deviation 7.10	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 3 Hours Postdose	2.0 mmHg Standard Deviation 10.43	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 4 Hours Postdose	1.2 mmHg Standard Deviation 8.84	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 6 Hours Postdose	1.6 mmHg Standard Deviation 7.06	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 8 Hours Postdose	2.3 mmHg Standard Deviation 9.25	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 12 Hours Postdose	0.7 mmHg Standard Deviation 9.63	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 14 Hours Postdose	3.1 mmHg Standard Deviation 8.10	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 6 (SAGE-217): 16 Hours Postdose	2.8 mmHg Standard Deviation 11.44	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): Predose	2.4 mmHg Standard Deviation 8.24	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	0.3 mmHg Standard Deviation 8.72	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 2 Hours Postdose	-2.0 mmHg Standard Deviation 7.54	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 3 Hours Postdose	-0.2 mmHg Standard Deviation 6.47	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 4 Hours Postdose	-1.4 mmHg Standard Deviation 9.98	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 6 Hours Postdose	-0.9 mmHg Standard Deviation 7.85	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 8 Hours Postdose	2.7 mmHg Standard Deviation 6.91	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	2.0 mmHg Standard Deviation 10.58	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 14 Hours Postdose	2.9 mmHg Standard Deviation 11.34	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 7 (SAGE-217): 16 Hours Postdose	1.1 mmHg Standard Deviation 9.31	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 8 (Follow-up)	2.1 mmHg Standard Deviation 7.47	—	—
CFB in Standing Diastolic Blood Pressure - Part A CFB at Day 14 (Follow-up)	1.5 mmHg Standard Deviation 8.06	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Pulse Oximetry- Part A Baseline	96.9 percentage Standard Deviation 2.22	—	—
CFB in Pulse Oximetry- Part A CFB at Day 1 (L/C): 1 Hour Postdose	-0.3 percentage Standard Deviation 1.03	—	—
CFB in Pulse Oximetry- Part A CFB at Day 1 (L/C): 2 Hours Postdose	0.2 percentage Standard Deviation 1.42	—	—
CFB in Pulse Oximetry- Part A CFB at Day 1 (L/C): 3 Hours Postdose	0.2 percentage Standard Deviation 1.90	—	—
CFB in Pulse Oximetry- Part A CFB at Day 1 (L/C): 4 Hours Postdose	0.1 percentage Standard Deviation 2.02	—	—
CFB in Pulse Oximetry- Part A CFB at Day 1 (L/C): 6 Hours Postdose	-0.2 percentage Standard Deviation 1.42	—	—
CFB in Pulse Oximetry- Part A CFB at Day 1 (L/C): 8 Hours Postdose	-0.1 percentage Standard Deviation 1.23	—	—
CFB in Pulse Oximetry- Part A CFB at Day 1 (L/C): 12 Hours Postdose	-0.1 percentage Standard Deviation 1.46	—	—
CFB in Pulse Oximetry- Part A CFB at Day 1 (L/C): 14 Hours Postdose	-0.4 percentage Standard Deviation 1.08	—	—
CFB in Pulse Oximetry- Part A CFB at Day 1 (L/C): 16 Hours Postdose	-0.7 percentage Standard Deviation 2.64	—	—
CFB in Pulse Oximetry- Part A CFB at Day 2 (L/C): Predose	-0.6 percentage Standard Deviation 1.50	—	—
CFB in Pulse Oximetry- Part A CFB at Day 2 (L/C): 1 Hour Postdose	-0.4 percentage Standard Deviation 2.02	—	—
CFB in Pulse Oximetry- Part A CFB at Day 2 (L/C): 2 Hours Postdose	-0.4 percentage Standard Deviation 1.83	—	—
CFB in Pulse Oximetry- Part A CFB at Day 2 (L/C): 3 Hours Postdose	-0.2 percentage Standard Deviation 0.97	—	—
CFB in Pulse Oximetry- Part A CFB at Day 2 (L/C): 4 Hours Postdose	-0.7 percentage Standard Deviation 2.02	—	—
CFB in Pulse Oximetry- Part A CFB at Day 2 (L/C): 6 Hours Postdose	-0.5 percentage Standard Deviation 2.38	—	—
CFB in Pulse Oximetry- Part A CFB at Day 2 (L/C): 8 Hours Postdose	0.4 percentage Standard Deviation 1.91	—	—
CFB in Pulse Oximetry- Part A CFB at Day 2 (L/C): 12 Hours Postdose	-0.1 percentage Standard Deviation 1.17	—	—
CFB in Pulse Oximetry- Part A CFB at Day 2 (L/C): 14 Hours Postdose	-0.6 percentage Standard Deviation 1.28	—	—
CFB in Pulse Oximetry- Part A CFB at Day 2 (L/C): 16 Hours Postdose	-0.2 percentage Standard Deviation 1.31	—	—
CFB in Pulse Oximetry- Part A CFB at Day 3 (L/C): Predose	-0.5 percentage Standard Deviation 1.79	—	—
CFB in Pulse Oximetry- Part A CFB at Day 3 (L/C): 1 Hour Postdose	-1.1 percentage Standard Deviation 1.86	—	—
CFB in Pulse Oximetry- Part A CFB at Day 3 (L/C): 2 Hours Postdose	-0.4 percentage Standard Deviation 1.70	—	—
CFB in Pulse Oximetry- Part A CFB at Day 3 (L/C): 3 Hours Postdose	-0.3 percentage Standard Deviation 1.44	—	—
CFB in Pulse Oximetry- Part A CFB at Day 3 (L/C): 4 Hours Postdose	-0.1 percentage Standard Deviation 1.33	—	—
CFB in Pulse Oximetry- Part A CFB at Day 3 (L/C): 6 Hours Postdose	0.3 percentage Standard Deviation 1.59	—	—
CFB in Pulse Oximetry- Part A CFB at Day 3 (L/C): 8 Hours Postdose	-0.1 percentage Standard Deviation 1.90	—	—
CFB in Pulse Oximetry- Part A CFB at Day 3 (L/C): 12 Hours Postdose	0.0 percentage Standard Deviation 1.36	—	—
CFB in Pulse Oximetry- Part A CFB at Day 3 (L/C): 14 Hours Postdose	0.4 percentage Standard Deviation 1.28	—	—
CFB in Pulse Oximetry- Part A CFB at Day 3 (L/C): 16 Hours Postdose	-0.2 percentage Standard Deviation 1.63	—	—
CFB in Pulse Oximetry- Part A CFB at Day 4 (SAGE-217): Predose	0.0 percentage Standard Deviation 0.96	—	—
CFB in Pulse Oximetry- Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	-1.6 percentage Standard Deviation 3.69	—	—
CFB in Pulse Oximetry- Part A CFB at Day 4 (SAGE-217): 2 Hours Postdose	-0.7 percentage Standard Deviation 2.73	—	—
CFB in Pulse Oximetry- Part A CFB at Day 4 (SAGE-217): 3 Hours Postdose	-0.1 percentage Standard Deviation 1.82	—	—
CFB in Pulse Oximetry- Part A CFB at Day 4 (SAGE-217): 4 Hours Postdose	-0.4 percentage Standard Deviation 1.09	—	—
CFB in Pulse Oximetry- Part A CFB at Day 4 (SAGE-217): 6 Hours Postdose	-0.4 percentage Standard Deviation 1.87	—	—
CFB in Pulse Oximetry- Part A CFB at Day 4 (SAGE-217): 8 Hours Postdose	-0.4 percentage Standard Deviation 1.28	—	—
CFB in Pulse Oximetry- Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	-0.1 percentage Standard Deviation 1.29	—	—
CFB in Pulse Oximetry- Part A CFB at Day 4 (SAGE-217): 14 Hours Postdose	-0.2 percentage Standard Deviation 1.42	—	—
CFB in Pulse Oximetry- Part A CFB at Day 4 (SAGE-217): 16 Hours Postdose	-0.3 percentage Standard Deviation 1.68	—	—
CFB in Pulse Oximetry- Part A CFB at Day 5 (SAGE-217): Predose	0.2 percentage Standard Deviation 1.76	—	—
CFB in Pulse Oximetry- Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	-1.3 percentage Standard Deviation 2.61	—	—
CFB in Pulse Oximetry- Part A CFB at Day 5 (SAGE-217): 2 Hours Postdose	-1.2 percentage Standard Deviation 2.72	—	—
CFB in Pulse Oximetry- Part A CFB at Day 5 (SAGE-217): 3 Hours Postdose	0.1 percentage Standard Deviation 1.82	—	—
CFB in Pulse Oximetry- Part A CFB at Day 5 (SAGE-217): 4 Hours Postdose	0.0 percentage Standard Deviation 1.36	—	—
CFB in Pulse Oximetry- Part A CFB at Day 5 (SAGE-217): 6 Hours Postdose	-0.2 percentage Standard Deviation 1.72	—	—
CFB in Pulse Oximetry- Part A CFB at Day 5 (SAGE-217): 8 Hours Postdose	-0.1 percentage Standard Deviation 1.73	—	—
CFB in Pulse Oximetry- Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	-0.4 percentage Standard Deviation 2.56	—	—
CFB in Pulse Oximetry- Part A CFB at Day 5 (SAGE-217): 14 Hours Postdose	-0.6 percentage Standard Deviation 2.34	—	—
CFB in Pulse Oximetry- Part A CFB at Day 5 (SAGE-217): 16 Hours Postdose	-1.1 percentage Standard Deviation 2.87	—	—
CFB in Pulse Oximetry- Part A CFB at Day 6 (SAGE-217): Predose	-0.5 percentage Standard Deviation 1.61	—	—
CFB in Pulse Oximetry- Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	-1.1 percentage Standard Deviation 1.59	—	—
CFB in Pulse Oximetry- Part A CFB at Day 6 (SAGE-217): 2 Hours Postdose	0.1 percentage Standard Deviation 2.37	—	—
CFB in Pulse Oximetry- Part A CFB at Day 6 (SAGE-217): 3 Hours Postdose	-0.9 percentage Standard Deviation 2.03	—	—
CFB in Pulse Oximetry- Part A CFB at Day 6 (SAGE-217): 4 Hours Postdose	-0.4 percentage Standard Deviation 2.34	—	—
CFB in Pulse Oximetry- Part A CFB at Day 6 (SAGE-217): 6 Hours Postdose	0.1 percentage Standard Deviation 2.09	—	—
CFB in Pulse Oximetry- Part A CFB at Day 6 (SAGE-217): 8 Hours Postdose	0.0 percentage Standard Deviation 1.52	—	—
CFB in Pulse Oximetry- Part A CFB at Day 6 (SAGE-217): 12 Hours Postdose	0.0 percentage Standard Deviation 1.84	—	—
CFB in Pulse Oximetry- Part A CFB at Day 6 (SAGE-217): 14 Hours Postdose	-0.4 percentage Standard Deviation 1.79	—	—
CFB in Pulse Oximetry- Part A CFB at Day 6 (SAGE-217): 16 Hours Postdose	0.1 percentage Standard Deviation 2.27	—	—
CFB in Pulse Oximetry- Part A CFB at Day 7 (SAGE-217): Predose	0.3 percentage Standard Deviation 1.38	—	—
CFB in Pulse Oximetry- Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	-1.4 percentage Standard Deviation 2.28	—	—
CFB in Pulse Oximetry- Part A CFB at Day 7 (SAGE-217): 2 Hours Postdose	-0.4 percentage Standard Deviation 2.92	—	—
CFB in Pulse Oximetry- Part A CFB at Day 7 (SAGE-217): 3 Hours Postdose	-0.5 percentage Standard Deviation 2.50	—	—
CFB in Pulse Oximetry- Part A CFB at Day 7 (SAGE-217): 4 Hours Postdose	0.4 percentage Standard Deviation 1.45	—	—
CFB in Pulse Oximetry- Part A CFB at Day 7 (SAGE-217): 6 Hours Postdose	0.3 percentage Standard Deviation 0.99	—	—
CFB in Pulse Oximetry- Part A CFB at Day 7 (SAGE-217): 8 Hours Postdose	0.3 percentage Standard Deviation 1.33	—	—
CFB in Pulse Oximetry- Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	0.3 percentage Standard Deviation 1.94	—	—
CFB in Pulse Oximetry- Part A CFB at Day 7 (SAGE-217): 14 Hours Postdose	0.3 percentage Standard Deviation 1.59	—	—
CFB in Pulse Oximetry- Part A CFB at Day 7 (SAGE-217): 16 Hours Postdose	0.2 percentage Standard Deviation 1.76	—	—
CFB in Pulse Oximetry- Part A CFB at Day 8 (Follow-up)	0.3 percentage Standard Deviation 1.27	—	—
CFB in Pulse Oximetry- Part A CFB at Day 14 (Follow-up)	0.5 percentage Standard Deviation 1.77	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A Baseline	64.7 beats/min Standard Deviation 11.85	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 3 (L/C): Predose	-0.5 beats/min Standard Deviation 6.77	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 4 (SAGE-217): Predose	1.3 beats/min Standard Deviation 6.78	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	6.9 beats/min Standard Deviation 7.65	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	7.1 beats/min Standard Deviation 8.89	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 5 (SAGE-217): Predose	2.5 beats/min Standard Deviation 5.53	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	8.2 beats/min Standard Deviation 5.31	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	9.0 beats/min Standard Deviation 10.71	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 6 (SAGE-217): Predose	3.7 beats/min Standard Deviation 4.50	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	5.9 beats/min Standard Deviation 7.11	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A Day 6 (SAGE-217): 12 Hours Postdose	8.5 beats/min Standard Deviation 5.37	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 7 (SAGE-217): Predose	5.9 beats/min Standard Deviation 8.76	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	6.2 beats/min Standard Deviation 6.03	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	10.7 beats/min Standard Deviation 6.78	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 8 (Follow-up)	0.9 beats/min Standard Deviation 4.17	—	—
CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A CFB at Day 14 (Follow-up)	4.7 beats/min Standard Deviation 9.32	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aggregate PR Interval - Part A Baseline	158.0 milliseconds (msec) Interval 122.0 to 228.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 3 (L/C): Predose	2.0 milliseconds (msec) Interval -16.0 to 26.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 4 (SAGE-217): Predose	-2.0 milliseconds (msec) Interval -9.0 to 17.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	-2.0 milliseconds (msec) Interval -20.0 to 25.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	-8.0 milliseconds (msec) Interval -26.0 to 22.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 5 (SAGE-217): Predose	-1.0 milliseconds (msec) Interval -18.0 to 13.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	-6.0 milliseconds (msec) Interval -24.0 to 17.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	-1.0 milliseconds (msec) Interval -32.0 to 18.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 6 (SAGE-217): Predose	-3.0 milliseconds (msec) Interval -18.0 to 21.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	-5.0 milliseconds (msec) Interval -25.0 to 22.0	—	—
CFB in Aggregate PR Interval - Part A Day 6 (SAGE-217): 12 Hours Postdose	-1.5 milliseconds (msec) Interval -30.0 to 15.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 7 (SAGE-217): Predose	-1.0 milliseconds (msec) Interval -26.0 to 14.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	-2.5 milliseconds (msec) Interval -32.0 to 19.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	-2.0 milliseconds (msec) Interval -18.0 to 20.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 8 (Follow-up)	-2.5 milliseconds (msec) Interval -24.0 to 20.0	—	—
CFB in Aggregate PR Interval - Part A CFB at Day 14 (Follow-up)	-8.0 milliseconds (msec) Interval -34.0 to 86.0	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aggregate RR Interval - Part A Baseline	950.0 milliseconds (msec) Interval 684.0 to 1226.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 3 (L/C): Predose	-32.5 milliseconds (msec) Interval -298.0 to 190.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 4 (SAGE-217): Predose	-43.5 milliseconds (msec) Interval -298.0 to 285.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	-99.0 milliseconds (msec) Interval -263.0 to 98.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	-98.5 milliseconds (msec) Interval -376.0 to 252.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 5 (SAGE-217): Predose	-56.0 milliseconds (msec) Interval -143.0 to 211.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	-102.0 milliseconds (msec) Interval -276.0 to -30.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	-133.0 milliseconds (msec) Interval -386.0 to 182.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 6 (SAGE-217): Predose	-65.0 milliseconds (msec) Interval -150.0 to 84.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	-63.0 milliseconds (msec) Interval -196.0 to 36.0	—	—
CFB in Aggregate RR Interval - Part A Day 6 (SAGE-217): 12 Hours Postdose	-113.5 milliseconds (msec) Interval -228.0 to 28.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 7 (SAGE-217): Predose	-76.5 milliseconds (msec) Interval -420.0 to 179.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	-104.5 milliseconds (msec) Interval -226.0 to 125.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	-120.0 milliseconds (msec) Interval -344.0 to 70.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 8 (Follow-up)	-10.0 milliseconds (msec) Interval -118.0 to 114.0	—	—
CFB in Aggregate RR Interval - Part A CFB at Day 14 (Follow-up)	-86.0 milliseconds (msec) Interval -189.0 to 169.0	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aggregate QT Interval - Part A Baseline	406.0 msec Interval 340.0 to 445.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 3 (L/C): Predose	-4.0 msec Interval -16.0 to 64.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 4 (SAGE-217): Predose	-4.5 msec Interval -39.0 to 39.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	-9.0 msec Interval -44.0 to 66.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	-15.5 msec Interval -92.0 to 84.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 5 (SAGE-217): Predose	-8.5 msec Interval -41.0 to 22.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	-12.0 msec Interval -42.0 to 24.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	-22.0 msec Interval -42.0 to 18.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 6 (SAGE-217): Predose	-4.5 msec Interval -33.0 to 30.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	-9.0 msec Interval -61.0 to 9.0	—	—
CFB in Aggregate QT Interval - Part A Day 6 (SAGE-217): 12 Hours Postdose	-13.0 msec Interval -35.0 to 26.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 7 (SAGE-217): Predose	-12.5 msec Interval -48.0 to 56.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	-13.0 msec Interval -50.0 to 20.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	-23.0 msec Interval -50.0 to 55.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 8 (Follow-up)	0.0 msec Interval -26.0 to 32.0	—	—
CFB in Aggregate QT Interval - Part A CFB at Day 14 (Follow-up)	-16.0 msec Interval -38.0 to 20.0	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aggregate QRS Duration - Part A Baseline	88.0 msec Interval 76.0 to 106.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 3 (L/C): Predose	-1.0 msec Interval -14.0 to 8.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 4 (SAGE-217): Predose	0.0 msec Interval -5.0 to 22.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	2.0 msec Interval -16.0 to 18.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	0.0 msec Interval -20.0 to 16.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 5 (SAGE-217): Predose	-2.0 msec Interval -18.0 to 16.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	0.0 msec Interval -14.0 to 12.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	-1.0 msec Interval -6.0 to 8.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 6 (SAGE-217): Predose	-2.0 msec Interval -16.0 to 15.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	-0.5 msec Interval -18.0 to 12.0	—	—
CFB in Aggregate QRS Duration - Part A Day 6 (SAGE-217): 12 Hours Postdose	0.0 msec Interval -14.0 to 21.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 7 (SAGE-217): Predose	-2.0 msec Interval -16.0 to 14.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	0.0 msec Interval -22.0 to 14.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	-1.5 msec Interval -12.0 to 13.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 8 (Follow-up)	-1.0 msec Interval -16.0 to 18.0	—	—
CFB in Aggregate QRS Duration - Part A CFB at Day 14 (Follow-up)	3.0 msec Interval -10.0 to 12.0	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aggregate QTcF Interval - Part A Baseline	419.0 msec Interval 386.0 to 435.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 3 (L/C): Predose	-1.0 msec Interval -21.0 to 39.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 4 (SAGE-217): Predose	2.0 msec Interval -32.0 to 33.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	-0.5 msec Interval -29.0 to 53.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	6.5 msec Interval -85.0 to 50.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 5 (SAGE-217): Predose	-3.0 msec Interval -65.0 to 28.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	2.0 msec Interval -19.0 to 31.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	-7.0 msec Interval -23.0 to 26.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 6 (SAGE-217): Predose	4.5 msec Interval -20.0 to 24.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	0.5 msec Interval -38.0 to 32.0	—	—
CFB in Aggregate QTcF Interval - Part A Day 6 (SAGE-217): 12 hours postdose	-2.5 msec Interval -14.0 to 34.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 7 (SAGE-217): Predose	2.0 msec Interval -16.0 to 32.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 7 (SAGE-217): 1 Hour Postdose	0.0 msec Interval -35.0 to 23.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	-2.5 msec Interval -17.0 to 46.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 8 (Follow-up)	-0.5 msec Interval -19.0 to 37.0	—	—
CFB in Aggregate QTcF Interval - Part A CFB at Day 14 (Follow-up)	-7.0 msec Interval -52.0 to 35.0	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa). Number analyzed = Number of participants with data available at the specific time point.

The SSS was a participant-rated scale designed to quickly assess how alert a participant was feeling. Degrees of sleepiness and alertness were rated on a scale of one to seven, where the lowest score of 'one' indicated the participant was 'feeling active, vital, alert, or wide awake' and the highest score of 'seven' indicated the participant was 'no longer fighting sleep, sleep onset soon; having dream-like thoughts'. A negative change from baseline indicated less sleepiness. A positive change from baseline indicated more sleepiness. Baseline is the last measurement taken before the first dose of study drug. L/C indicated levodopa/carbidopa. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Stanford Sleepiness Scale (SSS) Score - Part A Baseline	1.2 score on a scale Standard Deviation 0.56	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 1 (L/C): 1 Hour Postdose	-0.1 score on a scale Standard Deviation 0.26	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 1 (L/C): 2 Hours Postdose	-0.1 score on a scale Standard Deviation 0.26	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 1 (L/C): 3 Hours Postdose	-0.1 score on a scale Standard Deviation 0.52	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 1 (L/C): 4 Hours Postdose	0.0 score on a scale Standard Deviation 0.65	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 1 (L/C): 6 Hours Postdose	0.0 score on a scale Standard Deviation 0.76	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 1 (L/C): 8 Hours Postdose	0.4 score on a scale Standard Deviation 1.39	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 1 (L/C): 12 Hours Postdose	0.2 score on a scale Standard Deviation 0.58	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 1 (L/C): 14 Hours Postdose	0.6 score on a scale Standard Deviation 0.90	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 1 (L/C): 16 Hours Postdose	1.0 score on a scale Standard Deviation 0.85	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 2 (L/C): Predose	0.4 score on a scale Standard Deviation 0.74	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 2 (L/C): 1 Hour Postdose	0.3 score on a scale Standard Deviation 0.73	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 2 (L/C): 2 Hours Postdose	0.2 score on a scale Standard Deviation 0.58	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 2 (L/C): 3 Hours Postdose	0.5 score on a scale Standard Deviation 1.22	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 2 (L/C): 4 Hours Postdose	0.3 score on a scale Standard Deviation 0.91	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 2 (L/C): 6 Hours Postdose	0.5 score on a scale Standard Deviation 1.20	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 2 (L/C): 8 Hours Postdose	0.4 score on a scale Standard Deviation 0.96	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 2 (L/C): 12 Hours Postdose	0.3 score on a scale Standard Deviation 0.47	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 2 (L/C): 14 Hours Postdose	0.6 score on a scale Standard Deviation 0.94	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 2 (L/C): 16 Hours Postdose	0.7 score on a scale Standard Deviation 0.75	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 3 (L/C): Predose	0.3 score on a scale Standard Deviation 0.91	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 3 (L/C): 1 Hour Postdose	0.0 score on a scale Standard Deviation 0.68	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 3 (L/C): 2 Hours Postdose	0.3 score on a scale Standard Deviation 0.91	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 3 (L/C): 3 Hours Postdose	0.3 score on a scale Standard Deviation 1.07	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 3 (L/C): 4 Hours Postdose	0.4 score on a scale Standard Deviation 1.15	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 3 (L/C): 6 Hours Postdose	0.2 score on a scale Standard Deviation 0.90	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 3 (L/C): 8 Hours Postdose	0.3 score on a scale Standard Deviation 0.85	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 3 (L/C): 12 Hours Postdose	0.4 score on a scale Standard Deviation 1.01	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 3 (L/C): 14 Hours Postdose	1.0 score on a scale Standard Deviation 1.18	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 3 (L/C): 16 Hours Postdose	0.7 score on a scale Standard Deviation 0.79	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 4 (SAGE-217): Predose	0.3 score on a scale Standard Deviation 0.61	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 4 (SAGE-217): 1 Hour Postdose	3.2 score on a scale Standard Deviation 2.28	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 4 (SAGE-217): 2 Hours Postdose	2.6 score on a scale Standard Deviation 2.03	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 4 (SAGE-217): 3 Hours Postdose	2.0 score on a scale Standard Deviation 1.57	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 4 (SAGE-217): 4 Hours Postdose	1.2 score on a scale Standard Deviation 1.63	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 4 (SAGE-217): 6 Hours Postdose	0.4 score on a scale Standard Deviation 1.01	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 4 (SAGE-217): 8 Hours Postdose	0.2 score on a scale Standard Deviation 0.93	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 4 (SAGE-217): 12 Hours Postdose	0.2 score on a scale Standard Deviation 0.43	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 4 (SAGE-217): 14 Hours Postdose	0.2 score on a scale Standard Deviation 0.43	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 4 (SAGE-217): 16 Hours Postdose	1.0 score on a scale Standard Deviation 0.82	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 5 (SAGE-217): Predose	0.3 score on a scale Standard Deviation 0.47	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 5 (SAGE-217): 1 Hour Postdose	3.8 score on a scale Standard Deviation 1.79	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 5 (SAGE-217): 2 Hours Postdose	1.8 score on a scale Standard Deviation 1.68	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 5 (SAGE-217): 3 Hours Postdose	1.1 score on a scale Standard Deviation 1.38	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 5 (SAGE-217): 4 Hours Postdose	0.8 score on a scale Standard Deviation 1.42	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 5 (SAGE-217): 6 Hours Postdose	0.6 score on a scale Standard Deviation 0.96	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 5 (SAGE-217): 8 Hours Postdose	0.1 score on a scale Standard Deviation 0.47	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 5 (SAGE-217): 12 Hours Postdose	0.2 score on a scale Standard Deviation 0.43	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 5 (SAGE-217): 14 Hours Postdose	0.4 score on a scale Standard Deviation 0.94	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 5 (SAGE-217): 16 Hours Postdose	0.8 score on a scale Standard Deviation 1.07	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 6 (SAGE-217): Predose	0.1 score on a scale Standard Deviation 0.73	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 6 (SAGE-217): 1 Hour Postdose	2.6 score on a scale Standard Deviation 1.74	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 6 (SAGE-217): 2 Hours Postdose	1.8 score on a scale Standard Deviation 1.85	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 6 (SAGE-217): 3 Hours Postdose	1.6 score on a scale Standard Deviation 2.21	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 6 (SAGE-217): 4 Hours Postdose	1.1 score on a scale Standard Deviation 1.94	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 6 (SAGE-217): 6 Hours Postdose	0.8 score on a scale Standard Deviation 1.30	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 6 (SAGE-217): 8 Hours Postdose	0.3 score on a scale Standard Deviation 0.91	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 6 (SAGE-217): 12 Hours Postdose	0.2 score on a scale Standard Deviation 0.89	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 6 (SAGE-217): 14 Hours Postdose	0.4 score on a scale Standard Deviation 0.74	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 6 (SAGE-217): 16 Hours Postdose	0.9 score on a scale Standard Deviation 1.19	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 7 (SAGE-217): Predose	0.2 score on a scale Standard Deviation 0.58	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 7 (SAGE-217): 1 hour postdose	2.0 score on a scale Standard Deviation 1.66	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 7 (SAGE-217): 2 Hours Postdose	1.3 score on a scale Standard Deviation 1.38	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 7 (SAGE-217): 3 Hours Postdose	0.7 score on a scale Standard Deviation 1.14	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 7 (SAGE-217): 4 Hours Postdose	0.7 score on a scale Standard Deviation 1.33	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 7 (SAGE-217): 6 Hours Postdose	0.1 score on a scale Standard Deviation 0.86	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 7 (SAGE-217): 8 Hours Postdose	0.2 score on a scale Standard Deviation 0.97	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 7 (SAGE-217): 12 Hours Postdose	0.1 score on a scale Standard Deviation 0.83	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 7 (SAGE-217): 14 Hours Postdose	0.4 score on a scale Standard Deviation 1.01	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 7 (SAGE-217): 16 Hours Postdose	0.4 score on a scale Standard Deviation 1.01	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 8 (Follow-up)	-0.1 score on a scale Standard Deviation 0.62	—	—
CFB in Stanford Sleepiness Scale (SSS) Score - Part A CFB at Day 14 (Follow-up)	-0.1 score on a scale Standard Deviation 0.59	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug (SAGE-217 or levodopa).

The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included "yes" or "no"' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with a specific plan. The C-SSRS SB items involved actual attempt, interrupted attempt, aborted attempt, preparatory acts or behavior, suicidal behavior and suicide. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item - Part A Suicidal Ideation: Pre-treatment	0 percentage of participants	—	—
Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item - Part A Suicidal Ideation: Post-treatment	0 percentage of participants	—	—
Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item - Part A Suicidal Behavior: Pre-treatment	0 percentage of participants	—	—
Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation or Suicidal Behavior Item - Part A Suicidal Behavior: Post-treatment	0 percentage of participants	—	—

PRIMARY outcome

Timeframe: Baseline, Days 1 to 6 (12 and 23 hours postdose), Day 7 (12 hours postdose), Day 14

Population: The efficacy population included all participants in the safety population who received at least one dose of study drug and had at least one postdose MDS-UPDRS evaluation.

The modified MDS-UPDRS included 4 scales, with various subscales. Each item was rated from 0 (normal) to 4 (severe). The scales were Part I: nonmotor experiences of daily living (13 items); Part II: motor experiences of daily living (13 items); Part III: motor examination (33 scores based on 18 items [several with right, left or other body distribution scores]); and Part IV: motor complications (6 items). The Part II/III tremor score was calculated as the sum of 5 individual tremor item scores from Part II and Part III. The total score range for Part II/III is 0 to 44. Lower scores represent less symptom severity and higher scores represent more symptom severity. Baseline is the last measurement taken before the first dose of study drug. A negative change from baseline indicates an improvement in symptom severity. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B Baseline	19.1 score on a scale Standard Deviation 3.75	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-5.4 score on a scale Standard Deviation 4.52	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 1 (SAGE-217): 23 Hours Postdose	-5.9 score on a scale Standard Deviation 5.15	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-6.5 score on a scale Standard Deviation 5.45	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 2 (SAGE-217): 23 Hours Postdose	-6.6 score on a scale Standard Deviation 4.60	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-6.0 score on a scale Standard Deviation 4.51	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 3 (SAGE-217): 23 Hours Postdose	-5.9 score on a scale Standard Deviation 5.39	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-8.0 score on a scale Standard Deviation 5.53	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 4 (SAGE-217): 23 Hours Postdose	-7.4 score on a scale Standard Deviation 5.02	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-7.4 score on a scale Standard Deviation 7.81	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 5 (SAGE-217): 23 Hours Postdose	-8.0 score on a scale Standard Deviation 5.71	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-5.2 score on a scale Standard Deviation 6.93	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 6 (SAGE-217): 23 Hours Postdose	-8.4 score on a scale Standard Deviation 5.02	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-7.7 score on a scale Standard Deviation 4.63	—	—
CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B CFB at Day 14 (Follow-up)	-3.7 score on a scale Standard Deviation 4.34	—	—

SECONDARY outcome

Timeframe: Days 1 to 7 (2, 4, 8, and 12 hours postdose), Day 8 and Day 14

Population: The efficacy population included all participants in the safety population who received at least one dose of study drug and had at least one postdose MDS-UPDRS evaluation. Number analyzed = Number of participants with data available at the specific time point.

Part III of the MDS-UPDRS assessed 18 motor categories, some of which included right and left measurements: speech, facial expression, kinetic tremor of hands, rest tremor amplitude, postural tremor of hands, rigidity of neck and 4 extremities, finger taps, hand movement, pronation/supination, toe tapping, constancy of rest tremor, leg agility, arising from chair, posture, gait, freezing of gait, postural stability, global spontaneity of movement. Part III total score was calculated as the sum of individual item scores from these categories. Each item was rated from 0 (normal) to 4 (severe). The total score range for Part III is 0 to 132. Lower scores indicate less symptom severity. The analysis was performed in participants included in Part A of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
MDS-UPDRS Part III Total Score - Part A Day 1 (L/C): 2 Hours Postdose	25.4 score on a scale Standard Deviation 9.34	—	—
MDS-UPDRS Part III Total Score - Part A Day 1 (L/C): 4 Hours Postdose	30.0 score on a scale Standard Deviation 10.53	—	—
MDS-UPDRS Part III Total Score - Part A Day 1 (L/C): 8 Hours Postdose	34.3 score on a scale Standard Deviation 10.83	—	—
MDS-UPDRS Part III Total Score - Part A Day 1 (L/C): 12 Hours Postdose	35.1 score on a scale Standard Deviation 9.71	—	—
MDS-UPDRS Part III Total Score - Part A Day 2 (L/C): 2 Hours Postdose	27.1 score on a scale Standard Deviation 9.15	—	—
MDS-UPDRS Part III Total Score - Part A Day 2 (L/C): 4 Hours Postdose	31.1 score on a scale Standard Deviation 9.65	—	—
MDS-UPDRS Part III Total Score - Part A Day 2 (L/C): 8 Hours Postdose	35.1 score on a scale Standard Deviation 11.37	—	—
MDS-UPDRS Part III Total Score - Part A Day 2 (L/C): 12 Hours Postdose	36.1 score on a scale Standard Deviation 11.07	—	—
MDS-UPDRS Part III Total Score - Part A Day 3 (L/C): 2 Hours Postdose	26.5 score on a scale Standard Deviation 10.95	—	—
MDS-UPDRS Part III Total Score - Part A Day 3 (L/C): 4 Hours Postdose	29.0 score on a scale Standard Deviation 10.95	—	—
MDS-UPDRS Part III Total Score - Part A Day 3 (L/C): 8 Hours Postdose	35.2 score on a scale Standard Deviation 10.76	—	—
MDS-UPDRS Part III Total Score - Part A Day 3 (L/C): 12 Hours Postdose	36.2 score on a scale Standard Deviation 11.29	—	—
MDS-UPDRS Part III Total Score - Part A Day 4 (SAGE-217): 2 Hours Postdose	35.7 score on a scale Standard Deviation 14.57	—	—
MDS-UPDRS Part III Total Score - Part A Day 4 (SAGE-217): 4 Hours Postdose	30.9 score on a scale Standard Deviation 12.84	—	—
MDS-UPDRS Part III Total Score - Part A Day 4 (SAGE-217):8 Hours Postdose	33.4 score on a scale Standard Deviation 11.65	—	—
MDS-UPDRS Part III Total Score - Part A Day 4 (SAGE-217): 12 Hours Postdose	33.3 score on a scale Standard Deviation 13.19	—	—
MDS-UPDRS Part III Total Score - Part A Day 5 (SAGE-217): 2 Hours Postdose	33.8 score on a scale Standard Deviation 12.76	—	—
MDS-UPDRS Part III Total Score - Part A Day 5 (SAGE-217): 4 Hours Postdose	32.4 score on a scale Standard Deviation 12.69	—	—
MDS-UPDRS Part III Total Score - Part A Day 5 (SAGE-217): 8 Hours Postdose	30.9 score on a scale Standard Deviation 12.02	—	—
MDS-UPDRS Part III Total Score - Part A Day 5 (SAGE-217): 12 Hours Postdose	33.0 score on a scale Standard Deviation 12.15	—	—
MDS-UPDRS Part III Total Score - Part A Day 6 (SAGE-217): 2 Hours Postdose	31.5 score on a scale Standard Deviation 11.97	—	—
MDS-UPDRS Part III Total Score - Part A Day 6 (SAGE-217): 4 Hours Postdose	31.8 score on a scale Standard Deviation 9.66	—	—
MDS-UPDRS Part III Total Score - Part A Day 6 (SAGE-217): 8 Hours Postdose	32.7 score on a scale Standard Deviation 12.81	—	—
MDS-UPDRS Part III Total Score - Part A Day 6 (SAGE-217): 12 Hours Postdose	34.5 score on a scale Standard Deviation 11.19	—	—
MDS-UPDRS Part III Total Score - Part A Day 7 (SAGE-217): 2 Hours Postdose	36.4 score on a scale Standard Deviation 12.55	—	—
MDS-UPDRS Part III Total Score - Part A Day 7 (SAGE-217): 4 Hours Postdose	35.8 score on a scale Standard Deviation 11.92	—	—
MDS-UPDRS Part III Total Score - Part A Day 7 (SAGE-217): 8 Hours Postdose	36.0 score on a scale Standard Deviation 11.73	—	—
MDS-UPDRS Part III Total Score - Part A Day 7 (SAGE-217): 12 Hours Postdose	35.6 score on a scale Standard Deviation 11.03	—	—
MDS-UPDRS Part III Total Score - Part A Day 8 (Follow-up)	35.4 score on a scale Standard Deviation 10.54	—	—
MDS-UPDRS Part III Total Score - Part A Day 14 (Follow-up)	30.2 score on a scale Standard Deviation 13.00	—	—

SECONDARY outcome

Timeframe: Baseline, Days 1 to 6 (12 and 23 hours postdose), Day 7 (12 hours postdose), Day 14

Population: The efficacy population included all participants in the safety population who received at least one dose of study drug and had at least one postdose MDS-UPDRS evaluation.

Part III of the MDS-UPDRS assessed 18 motor categories, some of which included right and left measurements: speech, facial expression, kinetic tremor of hands, rest tremor amplitude, postural tremor of hands, rigidity of neck and 4 extremities, finger taps, hand movement, pronation/supination, toe tapping, constancy of rest tremor, leg agility, arising from chair, posture, gait, freezing of gait, postural stability, global spontaneity of movement. Part III total score was calculated as the sum of the individual item scores from these categories. Each item was rated from 0 (normal) to 4 (severe). The total score range for Part III is 0 to 132. Lower scores represent less symptom severity. A negative change from baseline indicates an improvement in symptom severity. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in the MDS-UPDRS Part III Total Score - Part B Baseline	52.4 score on a scale Standard Deviation 12.00	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-8.4 score on a scale Standard Deviation 8.74	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 1 (SAGE-217): 23 Hours Postdose	-10.8 score on a scale Standard Deviation 9.90	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-11.6 score on a scale Standard Deviation 12.83	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 2 (SAGE-217): 23 Hours Postdose	-13.5 score on a scale Standard Deviation 7.87	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-12.4 score on a scale Standard Deviation 10.51	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 3 (SAGE-217): 23 Hours Postdose	-10.9 score on a scale Standard Deviation 9.39	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-14.3 score on a scale Standard Deviation 12.25	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 4 (SAGE-217): 23 Hours Postdose	-14.8 score on a scale Standard Deviation 10.30	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-14.5 score on a scale Standard Deviation 15.52	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 5 (SAGE-217): 23 Hours Postdose	-18.1 score on a scale Standard Deviation 10.10	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-14.8 score on a scale Standard Deviation 11.81	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 6 (SAGE-217): 23 Hours Postdose	-19.5 score on a scale Standard Deviation 9.30	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-18.6 score on a scale Standard Deviation 9.51	—	—
CFB in the MDS-UPDRS Part III Total Score - Part B CFB at Day 14 (Follow-up)	-14.5 score on a scale Standard Deviation 10.54	—	—

SECONDARY outcome

Timeframe: Baseline, Day 7 (12 hours postdose), Day 14

Population: The efficacy population included all participants in the safety population who received at least one dose of study drug and had at least one postdose MDS-UPDRS evaluation.

Part I of the MDS-UPDRS assessed 13 nonmotor experiences of daily living categories. Part I total score was calculated as the sum of the individual item scores from these categories. The total score range for Part I is 0 to 52. Lower scores indicate less symptom severity. A negative change from baseline indicates an improvement in symptom severity. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in the MDS-UPDRS Part I Total Score - Part B Baseline	9.9 score on a scale Standard Deviation 6.33	—	—
CFB in the MDS-UPDRS Part I Total Score - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-4.7 score on a scale Standard Deviation 6.54	—	—
CFB in the MDS-UPDRS Part I Total Score - Part B CFB at Day 14 (Follow-up)	-3.9 score on a scale Standard Deviation 6.05	—	—

SECONDARY outcome

Timeframe: Baseline, Days 1 to 6 (12 and 23 hours postdose), Day 7 (12 hours postdose), Day 14

Population: The efficacy population included all participants in the safety population who received at least one dose of study drug and had at least one postdose MDS-UPDRS evaluation.

Part II of the MDS-UPDRS assessed 13 categories of motor experiences of daily living: speech, salivation and drooling, chewing and swallowing, eating tasks, dressing, hygiene, handwriting, doing hobbies and other activities, turning in bed, tremor, getting out of bed, car, or deep chair, walking and balance, and freezing. The Part II total score was calculated as the sum of the individual item scores from these categories. The total score range for Part II is 0 to 52. Lower scores indicate less symptom severity. A negative change from baseline indicates an improvement in symptom severity. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in the MDS-UPDRS Part II Total Score - Part B Baseline	15.1 score on a scale Standard Deviation 8.26	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-1.9 score on a scale Standard Deviation 3.46	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 1 (SAGE-217): 23 Hours Postdose	-1.7 score on a scale Standard Deviation 3.73	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-2.1 score on a scale Standard Deviation 5.17	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 2 (SAGE-217): 23 Hours Postdose	-2.2 score on a scale Standard Deviation 4.92	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-2.0 score on a scale Standard Deviation 5.48	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 3 (SAGE-217): 23 Hours Postdose	-3.1 score on a scale Standard Deviation 4.20	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-3.4 score on a scale Standard Deviation 6.33	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 4 (SAGE-217): 23 Hours Postdose	-2.4 score on a scale Standard Deviation 5.43	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-4.6 score on a scale Standard Deviation 5.71	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 5 (SAGE-217): 23 Hours Postdose	-2.9 score on a scale Standard Deviation 4.90	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-2.9 score on a scale Standard Deviation 5.05	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 6 (SAGE-217): 23 Hours Postdose	-3.9 score on a scale Standard Deviation 5.40	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-3.9 score on a scale Standard Deviation 4.34	—	—
CFB in the MDS-UPDRS Part II Total Score - Part B CFB at Day 14 (Follow-up)	-3.9 score on a scale Standard Deviation 5.02	—	—

SECONDARY outcome

Timeframe: Baseline, Day 7 (12 hours postdose), Day 14

Population: The efficacy population included all participants in the safety population who received at least one dose of study drug and had at least one postdose MDS-UPDRS evaluation.

The MDS-UPDRS assesses nonmotor experiences, motor experiences, motor skills, and motor complication categories. The MDS-UPDRS Part I-IV total score was calculated as the sum of the individual item scores from these categories. The total score range for Part I-IV is 0 to 260. Lower scores indicate less symptom severity. A negative change from baseline indicates an improvement in symptom severity. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in the MDS-UPDRS Part I-IV Total Score - Part B Baseline	84.6 score on a scale Standard Deviation 24.01	—	—
CFB in the MDS-UPDRS Part I-IV Total Score - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-30.0 score on a scale Standard Deviation 17.71	—	—
CFB in the MDS-UPDRS Part I-IV Total Score - Part B CFB at Day 14 (Follow-up)	-24.1 score on a scale Standard Deviation 20.75	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was as an AE that occurred after the first administration of study drug. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 n=14 Participants Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
Percentage of Participants With TEAEs - Part B	57.1 percentage of participants	0 percentage of participants	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Severity was assessed according to the following scale: mild (awareness of sign or symptom, but easily tolerated); moderate (discomfort sufficient to cause interference with normal activities); severe (incapacitating, with inability to perform normal activities). The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 n=14 Participants Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
Percentage of Participants With TEAEs, Graded by Severity - Part B Mild	42.9 percentage of participants	0 percentage of participants	—
Percentage of Participants With TEAEs, Graded by Severity - Part B Moderate	14.3 percentage of participants	0 percentage of participants	—
Percentage of Participants With TEAEs, Graded by Severity - Part B Severe	0 percentage of participants	0 percentage of participants	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Basophils - Part B Baseline	0.06 10^9 cells/L Standard Deviation 0.074	—	—
CFB in Basophils - Part B CFB at Dose 4 (SAGE-217): Predose	0.02 10^9 cells/L Standard Deviation 0.089	—	—
CFB in Basophils - Part B CFB at Dose 6 (SAGE-217): Predose	0.02 10^9 cells/L Standard Deviation 0.058	—	—
CFB in Basophils - Part B CFB at Day 8 (Follow-up)	-0.03 10^9 cells/L Standard Deviation 0.061	—	—
CFB in Basophils - Part B CFB at Day 14 (Follow-up)	0.00 10^9 cells/L Standard Deviation 0.055	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Basophils to Leukocytes Ratio (%) - Part B Baseline	1.0 percentage Standard Deviation 0.39	—	—
CFB in Basophils to Leukocytes Ratio (%) - Part B CFB at Dose 4 (SAGE-217): Predose	0.2 percentage Standard Deviation 0.97	—	—
CFB in Basophils to Leukocytes Ratio (%) - Part B CFB at Dose 6 (SAGE-217): Predose	0.1 percentage Standard Deviation 1.00	—	—
CFB in Basophils to Leukocytes Ratio (%) - Part B CFB at Day 8 (Follow-up)	-0.1 percentage Standard Deviation 0.47	—	—
CFB in Basophils to Leukocytes Ratio (%) - Part B CFB at Day 14 (Follow-up)	0.1 percentage Standard Deviation 0.73	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Eosinophils - Part B Baseline	0.12 10^9 cells/L Standard Deviation 0.058	—	—
CFB in Eosinophils - Part B CFB at Dose 4 (SAGE-217): Predose	0.05 10^9 cells/L Standard Deviation 0.065	—	—
CFB in Eosinophils - Part B CFB at Dose 6 (SAGE-217): Predose	0.03 10^9 cells/L Standard Deviation 0.083	—	—
CFB in Eosinophils - Part B CFB at Day 8 (Follow-up)	0.03 10^9 cells/L Standard Deviation 0.114	—	—
CFB in Eosinophils - Part B CFB at Day 14 (Follow-up)	-0.02 10^9 cells/L Standard Deviation 0.058	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Eosinophils to Leukocytes Ratio (%) - Part B Baseline	2.0 percentage Standard Deviation 1.04	—	—
CFB in Eosinophils to Leukocytes Ratio (%) - Part B CFB at Dose 4 (SAGE-217): Predose	0.7 percentage Standard Deviation 1.20	—	—
CFB in Eosinophils to Leukocytes Ratio (%) - Part B CFB at Dose 6 (SAGE-217): Predose	0.1 percentage Standard Deviation 0.95	—	—
CFB in Eosinophils to Leukocytes Ratio (%) - Part B CFB at Day 8 (Follow-up)	0.4 percentage Standard Deviation 2.06	—	—
CFB in Eosinophils to Leukocytes Ratio (%) - Part B CFB at Day 14 (Follow-up)	-0.4 percentage Standard Deviation 0.93	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Erythrocytes - Part B Baseline	4.65 10^12 cells/L Standard Deviation 0.335	—	—
CFB in Erythrocytes - Part B CFB at Dose 4 (SAGE-217): Predose	0.16 10^12 cells/L Standard Deviation 0.798	—	—
CFB in Erythrocytes - Part B CFB at Dose 6 (SAGE-217): Predose	-0.11 10^12 cells/L Standard Deviation 0.186	—	—
CFB in Erythrocytes - Part B CFB at Day 8 (Follow-up)	-0.02 10^12 cells/L Standard Deviation 0.208	—	—
CFB in Erythrocytes - Part B CFB at Day 14 (Follow-up)	-0.06 10^12 cells/L Standard Deviation 0.101	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Hematocrit - Part B Baseline	0.436 L/L Standard Deviation 0.0357	—	—
CFB in Hematocrit - Part B CFB at Dose 4 (SAGE-217): Predose	0.023 L/L Standard Deviation 0.0775	—	—
CFB in Hematocrit - Part B CFB at Dose 6 (SAGE-217): Predose	-0.011 L/L Standard Deviation 0.0182	—	—
CFB in Hematocrit - Part B CFB at Day 8 (Follow-up)	0.006 L/L Standard Deviation 0.0268	—	—
CFB in Hematocrit - Part B CFB at Day 14 (Follow-up)	-0.002 L/L Standard Deviation 0.0119	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Hemoglobin - Part B Baseline	140.1 g/L Standard Deviation 14.22	—	—
CFB in Hemoglobin - Part B CFB at Dose 4 (SAGE-217): Predose	4.9 g/L Standard Deviation 20.90	—	—
CFB in Hemoglobin - Part B CFB at Dose 6 (SAGE-217): Predose	-1.4 g/L Standard Deviation 5.32	—	—
CFB in Hemoglobin - Part B CFB at Day 8 (Follow-up)	1.8 g/L Standard Deviation 6.03	—	—
CFB in Hemoglobin - Part B CFB at Day 14 (Follow-up)	-0.7 g/L Standard Deviation 4.48	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Leukocytes - Part B Baseline	6.47 10^9 cells/L Standard Deviation 1.322	—	—
CFB in Leukocytes - Part B CFB at Dose 4 (SAGE-217): Predose	0.85 10^9 cells/L Standard Deviation 2.677	—	—
CFB in Leukocytes - Part B CFB at Dose 6 (SAGE-217): Predose	0.31 10^9 cells/L Standard Deviation 1.370	—	—
CFB in Leukocytes - Part B CFB at Day 8 (Follow-up)	-0.21 10^9 cells/L Standard Deviation 0.935	—	—
CFB in Leukocytes - Part B CFB at Day 14 (Follow-up)	0.29 10^9 cells/L Standard Deviation 1.287	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Lymphocytes - Part B Baseline	1.68 10^9 cells/L Standard Deviation 0.549	—	—
CFB in Lymphocytes - Part B CFB at Dose 4 (SAGE-217): Predose	0.44 10^9 cells/L Standard Deviation 0.857	—	—
CFB in Lymphocytes - Part B CFB at Dose 6 (SAGE-217): Predose	0.26 10^9 cells/L Standard Deviation 0.386	—	—
CFB in Lymphocytes - Part B CFB at Day 8 (Follow-up)	0.18 10^9 cells/L Standard Deviation 0.283	—	—
CFB in Lymphocytes - Part B CFB at Day 14 (Follow-up)	0.11 10^9 cells/L Standard Deviation 0.373	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Lymphocytes to Leukocytes Ratio (%) - Part B Baseline	26.0 percentage Standard Deviation 6.31	—	—
CFB in Lymphocytes to Leukocytes Ratio (%) - Part B CFB at Dose 4 (SAGE-217): Predose	2.5 percentage Standard Deviation 6.15	—	—
CFB in Lymphocytes to Leukocytes Ratio (%) - Part B CFB at Dose 6 (SAGE-217): Predose	2.6 percentage Standard Deviation 5.34	—	—
CFB in Lymphocytes to Leukocytes Ratio (%) - Part B CFB at Day 8 (Follow-up)	3.4 percentage Standard Deviation 5.57	—	—
CFB in Lymphocytes to Leukocytes Ratio (%) - Part B CFB at Day 14 (Follow-up)	0.6 percentage Standard Deviation 5.73	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Monocytes - Part B Baseline	0.40 10^9 cells/L Standard Deviation 0.096	—	—
CFB in Monocytes - Part B CFB at Dose 4 (SAGE-217): Predose	0.09 10^9 cells/L Standard Deviation 0.194	—	—
CFB in Monocytes - Part B CFB at Dose 6 (SAGE-217): Predose	0.03 10^9 cells/L Standard Deviation 0.083	—	—
CFB in Monocytes - Part B CFB at Day 8 (Follow-up)	0.03 10^9 cells/L Standard Deviation 0.133	—	—
CFB in Monocytes - Part B CFB at Day 14 (Follow-up)	0.01 10^9 cells/L Standard Deviation 0.110	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Monocytes to Leukocytes Ratio (%) - Part B Baseline	6.4 percentage Standard Deviation 1.55	—	—
CFB in Monocytes to Leukocytes Ratio (%) - Part B CFB at Dose 4 (SAGE-217): Predose	0.3 percentage Standard Deviation 1.68	—	—
CFB in Monocytes to Leukocytes Ratio (%) - Part B CFB at Dose 6 (SAGE-217): Predose	0.1 percentage Standard Deviation 1.49	—	—
CFB in Monocytes to Leukocytes Ratio (%) - Part B CFB at Day 8 (Follow-up)	0.4 percentage Standard Deviation 1.74	—	—
CFB in Monocytes to Leukocytes Ratio (%) - Part B CFB at Day 14 (Follow-up)	-0.1 percentage Standard Deviation 1.07	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Neutrophils - Part B Baseline	4.23 10^9 cells/L Standard Deviation 0.957	—	—
CFB in Neutrophils - Part B CFB at Dose 4 (SAGE-217): Predose	0.23 10^9 cells/L Standard Deviation 1.842	—	—
CFB in Neutrophils - Part B CFB at Dose 6 (SAGE-217): Predose	0.00 10^9 cells/L Standard Deviation 1.136	—	—
CFB in Neutrophils - Part B CFB at Day 8 (Follow-up)	-0.43 10^9 cells/L Standard Deviation 0.902	—	—
CFB in Neutrophils - Part B CFB at Day 14 (Follow-up)	0.16 10^9 cells/L Standard Deviation 1.153	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Neutrophils to Leukocytes Ratio (%) - Part B Baseline	65.3 percentage Standard Deviation 5.28	—	—
CFB in Neutrophils to Leukocytes Ratio (%) - Part B CFB at Dose 4 (SAGE-217): Predose	-4.2 percentage Standard Deviation 7.50	—	—
CFB in Neutrophils to Leukocytes Ratio (%) - Part B CFB at Dose 6 (SAGE-217): Predose	-3.0 percentage Standard Deviation 6.64	—	—
CFB in Neutrophils to Leukocytes Ratio (%) - Part B CFB at Day 8 (Follow-up)	-4.4 percentage Standard Deviation 6.69	—	—
CFB in Neutrophils to Leukocytes Ratio (%) - Part B CFB at Day 14 (Follow-up)	-0.4 percentage Standard Deviation 6.69	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Platelets - Part B Baseline	189.2 10^9 cells/L Standard Deviation 37.72	—	—
CFB in Platelets - Part B CFB at Dose 4 (SAGE-217): Predose	24.1 10^9 cells/L Standard Deviation 67.75	—	—
CFB in Platelets - Part B CFB at Dose 6 (SAGE-217): Predose	5.9 10^9 cells/L Standard Deviation 13.64	—	—
CFB in Platelets - Part B CFB at Day 8 (Follow-up)	0.8 10^9 cells/L Standard Deviation 20.01	—	—
CFB in Platelets - Part B CFB at Day 14 (Follow-up)	5.3 10^9 cells/L Standard Deviation 19.58	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Reticulocytes - Part B Baseline	59.3 10^9 cells/L Standard Deviation 19.27	—	—
CFB in Reticulocytes - Part B CFB at Dose 4 (SAGE-217): Predose	1.1 10^9 cells/L Standard Deviation 11.35	—	—
CFB in Reticulocytes - Part B CFB at Dose 6 (SAGE-217): Predose	5.1 10^9 cells/L Standard Deviation 19.61	—	—
CFB in Reticulocytes - Part B CFB at Day 8 (Follow-up)	2.4 10^9 cells/L Standard Deviation 15.55	—	—
CFB in Reticulocytes - Part B CFB at Day 14 (Follow-up)	5.1 10^9 cells/L Standard Deviation 20.99	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, reticulocytes and reticulocytes to erythrocytes ratio. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Reticulocytes to Erythrocytes Ratio (%) - Part B Baseline	1.28 percentage Standard Deviation 0.417	—	—
CFB in Reticulocytes to Erythrocytes Ratio (%) - Part B CFB at Dose 4 (SAGE-217): Predose	0.04 percentage Standard Deviation 0.250	—	—
CFB in Reticulocytes to Erythrocytes Ratio (%) - Part B CFB at Dose 6 (SAGE-217): Predose	0.13 percentage Standard Deviation 0.410	—	—
CFB in Reticulocytes to Erythrocytes Ratio (%) - Part B CFB at Day 8 (Follow-up)	0.05 percentage Standard Deviation 0.334	—	—
CFB in Reticulocytes to Erythrocytes Ratio (%) - Part B CFB at Day 14 (Follow-up)	0.13 percentage Standard Deviation 0.486	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio and prothrombin time. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Activated Partial Thromboplastin Time - Part B Baseline	25.05 sec Interval 22.0 to 27.5	—	—
CFB in Activated Partial Thromboplastin Time - Part B CFB at Dose 4 (SAGE-217): Predose	-0.40 sec Interval -2.1 to 0.2	—	—
CFB in Activated Partial Thromboplastin Time - Part B CFB at Dose 6 (SAGE-217): Predose	-0.05 sec Interval -1.7 to 1.2	—	—
CFB in Activated Partial Thromboplastin Time - Part B CFB at Day 8 (Follow-up)	-0.30 sec Interval -1.6 to 0.5	—	—
CFB in Activated Partial Thromboplastin Time - Part B CFB at Day 14 (Follow-up)	-0.20 sec Interval -1.4 to 1.7	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio and prothrombin time. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Prothrombin International Normalized Ratio - Part B Baseline	0.98 ratio Standard Deviation 0.043	—	—
CFB in Prothrombin International Normalized Ratio - Part B CFB at Dose 4 (SAGE-217): Predose	-0.03 ratio Standard Deviation 0.045	—	—
CFB in Prothrombin International Normalized Ratio - Part B CFB at Dose 6 (SAGE-217): Predose	-0.01 ratio Standard Deviation 0.051	—	—
CFB in Prothrombin International Normalized Ratio - Part B CFB at Day 8 (Follow-up)	0.00 ratio Standard Deviation 0.041	—	—
CFB in Prothrombin International Normalized Ratio - Part B CFB at Day 14 (Follow-up)	0.01 ratio Standard Deviation 0.036	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio and prothrombin time. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Prothrombin Time - Part B Baseline	10.60 sec Interval 9.6 to 11.0	—	—
CFB in Prothrombin Time - Part B CFB at Dose 4 (SAGE-217): Predose	-0.20 sec Interval -0.8 to 0.6	—	—
CFB in Prothrombin Time - Part B CFB at Dose 6 (SAGE-217): Predose	-0.05 sec Interval -0.5 to 0.5	—	—
CFB in Prothrombin Time - Part B CFB at Day 8 (Follow-up)	-0.10 sec Interval -0.4 to 0.5	—	—
CFB in Prothrombin Time - Part B CFB at Day 14 (Follow-up)	0.10 sec Interval -0.3 to 0.6	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Alanine Aminotransferase - Part B Baseline	10.0 U/L Standard Deviation 6.66	—	—
CFB in Alanine Aminotransferase - Part B CFB at Dose 4 (SAGE-217): Predose	0.3 U/L Standard Deviation 3.17	—	—
CFB in Alanine Aminotransferase - Part B CFB at Dose 6 (SAGE-217): Predose	2.6 U/L Standard Deviation 5.42	—	—
CFB in Alanine Aminotransferase - Part B CFB at Day 8 (Follow-up)	1.9 U/L Standard Deviation 3.79	—	—
CFB in Alanine Aminotransferase - Part B CFB at Day 14 (Follow-up)	-0.2 U/L Standard Deviation 3.70	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Albumin - Part B Baseline	44.2 g/L Standard Deviation 2.75	—	—
CFB in Albumin - Part B CFB at Dose 4 (SAGE-217): Predose	-0.2 g/L Standard Deviation 1.40	—	—
CFB in Albumin - Part B CFB at Dose 6 (SAGE-217): Predose	-0.6 g/L Standard Deviation 1.65	—	—
CFB in Albumin - Part B CFB at Day 8 (Follow-up)	0.16 g/L Standard Deviation 1.45	—	—
CFB in Albumin - Part B CFB at Day 14 (Follow-up)	-0.1 g/L Standard Deviation 1.86	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Alkaline Phosphatase - Part B Baseline	84.0 U/L Standard Deviation 22.05	—	—
CFB in Alkaline Phosphatase - Part B CFB at Dose 4 (SAGE-217): Predose	1.4 U/L Standard Deviation 7.55	—	—
CFB in Alkaline Phosphatase - Part B CFB at Dose 6 (SAGE-217): Predose	2.1 U/L Standard Deviation 3.23	—	—
CFB in Alkaline Phosphatase - Part B CFB at Day 8 (Follow-up)	2.2 U/L Standard Deviation 8.85	—	—
CFB in Alkaline Phosphatase - Part B CFB at Day 14 (Follow-up)	-1.1 U/L Standard Deviation 8.69	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aspartate Aminotransferase - Part B Baseline	17.7 U/L Standard Deviation 10.59	—	—
CFB in Aspartate Aminotransferase - Part B CFB at Dose 4 (SAGE-217): Predose	-2.8 U/L Standard Deviation 10.63	—	—
CFB in Aspartate Aminotransferase - Part B CFB at Dose 6 (SAGE-217): Predose	-1.4 U/L Standard Deviation 10.93	—	—
CFB in Aspartate Aminotransferase - Part B CFB at Day 8 (Follow-up)	-0.4 U/L Standard Deviation 11.51	—	—
CFB in Aspartate Aminotransferase - Part B CFB at Day 14 (Follow-up)	-2.4 U/L Standard Deviation 10.12	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Bicarbonate - Part B Baseline	24.6 mmol/L Standard Deviation 1.74	—	—
CFB in Bicarbonate - Part B CFB at Dose 4 (SAGE-217): Predose	-1.2 mmol/L Standard Deviation 1.90	—	—
CFB in Bicarbonate - Part B CFB at Dose 6 (SAGE-217): Predose	-0.9 mmol/L Standard Deviation 2.06	—	—
CFB in Bicarbonate - Part B CFB at Day 8 (Follow-up)	-1.1 mmol/L Standard Deviation 2.23	—	—
CFB in Bicarbonate - Part B CFB at Day 14 (Follow-up)	-0.3 mmol/L Standard Deviation 1.77	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Bilirubin - Part B Baseline	8.306 umol/L Standard Deviation 2.4050	—	—
CFB in Bilirubin - Part B CFB at Dose 4 (SAGE-217): Predose	-2.993 umol/L Standard Deviation 2.4320	—	—
CFB in Bilirubin - Part B CFB at Dose 6 (SAGE-217): Predose	-2.795 umol/L Standard Deviation 2.0751	—	—
CFB in Bilirubin - Part B CFB at Day 8 (Follow-up)	-0.122 umol/L Standard Deviation 2.4611	—	—
CFB in Bilirubin - Part B CFB at Day 14 (Follow-up)	0.366 umol/L Standard Deviation 3.0129	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Calcium - Part B Baseline	2.340 mmol/L Standard Deviation 0.0796	—	—
CFB in Calcium - Part B CFB at Dose 4 (SAGE-217): Predose	0.006 mmol/L Standard Deviation 0.0859	—	—
CFB in Calcium - Part B CFB at Dose 6 (SAGE-217): Predose	0.002 mmol/L Standard Deviation 0.0599	—	—
CFB in Calcium - Part B CFB at Day 8 (Follow-up)	0.023 mmol/L Standard Deviation 0.0638	—	—
CFB in Calcium - Part B CFB at Day 14 (Follow-up)	-0.027 mmol/L Standard Deviation 0.0709	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Chloride - Part B Baseline	102.1 mmol/L Standard Deviation 2.03	—	—
CFB in Chloride - Part B CFB at Dose 4 (SAGE-217): Predose	0.1 mmol/L Standard Deviation 1.38	—	—
CFB in Chloride - Part B CFB at Dose 6 (SAGE-217): Predose	0.2 mmol/L Standard Deviation 1.53	—	—
CFB in Chloride - Part B CFB at Day 8 (Follow-up)	-0.5 mmol/L Standard Deviation 2.10	—	—
CFB in Chloride - Part B CFB at Day 14 (Follow-up)	-0.2 mmol/L Standard Deviation 2.36	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Creatinine - Part B Baseline	80.381 umol/L Standard Deviation 23.1753	—	—
CFB in Creatinine - Part B CFB at Dose 4 (SAGE-217): Predose	11.345 umol/L Standard Deviation 17.8035	—	—
CFB in Creatinine - Part B CFB at Dose 6 (SAGE-217): Predose	2.084 umol/L Standard Deviation 12.3449	—	—
CFB in Creatinine - Part B CFB at Day 8 (Follow-up)	-2.968 umol/L Standard Deviation 8.0917	—	—
CFB in Creatinine - Part B CFB at Day 14 (Follow-up)	-0.253 umol/L Standard Deviation 10.0339	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Lipase - Part B Baseline	37.2 U/L Standard Deviation 16.74	—	—
CFB in Lipase - Part B CFB at Dose 4 (SAGE-217): Predose	15.4 U/L Standard Deviation 9.64	—	—
CFB in Lipase - Part B CFB at Dose 6 (SAGE-217): Predose	19.4 U/L Standard Deviation 16.88	—	—
CFB in Lipase - Part B CFB at Day 8 (Follow-up)	4.3 U/L Standard Deviation 6.08	—	—
CFB in Lipase - Part B CFB at Day 14 (Follow-up)	1.6 U/L Standard Deviation 9.30	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Magnesium - Part B Baseline	0.873 mmol/L Standard Deviation 0.0489	—	—
CFB in Magnesium - Part B CFB at Dose 4 (SAGE-217): Predose	-0.014 mmol/L Standard Deviation 0.0536	—	—
CFB in Magnesium - Part B CFB at Dose 6 (SAGE-217): Predose	-0.009 mmol/L Standard Deviation 0.0401	—	—
CFB in Magnesium - Part B CFB at Day 8 (Follow-up)	0.018 mmol/L Standard Deviation 0.0448	—	—
CFB in Magnesium - Part B CFB at Day 14 (Follow-up)	-0.012 mmol/L Standard Deviation 0.0591	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Phosphate - Part B Baseline	1.091 mmol/L Standard Deviation 0.1489	—	—
CFB in Phosphate - Part B CFB at Dose 4 (SAGE-217): Predose	0.161 mmol/L Standard Deviation 0.1496	—	—
CFB in Phosphate - Part B CFB at Dose 6 (SAGE-217): Predose	0.180 mmol/L Standard Deviation 0.1386	—	—
CFB in Phosphate - Part B CFB at Day 8 (Follow-up)	0.042 mmol/L Standard Deviation 0.1775	—	—
CFB in Phosphate - Part B CFB at Day 14 (Follow-up)	0.009 mmol/L Standard Deviation 0.1939	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Potassium - Part B Baseline	4.57 mmol/L Standard Deviation 0.292	—	—
CFB in Potassium - Part B CFB at Dose 4 (SAGE-217): Predose	0.03 mmol/L Standard Deviation 0.319	—	—
CFB in Potassium - Part B CFB at Dose 6 (SAGE-217): Predose	-0.11 mmol/L Standard Deviation 0.264	—	—
CFB in Potassium - Part B CFB at Day 8 (Follow-up)	-0.11 mmol/L Standard Deviation 0.295	—	—
CFB in Potassium - Part B CFB at Day 14 (Follow-up)	-0.01 mmol/L Standard Deviation 0.268	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Protein - Part B Baseline	69.6 g/L Standard Deviation 5.40	—	—
CFB in Protein - Part B CFB at Dose 4 (SAGE-217): Predose	-0.8 g/L Standard Deviation 1.75	—	—
CFB in Protein - Part B CFB at Dose 6 (SAGE-217): Predose	-0.9 g/L Standard Deviation 3.00	—	—
CFB in Protein - Part B CFB at Day 8 (Follow-up)	0.9 g/L Standard Deviation 2.68	—	—
CFB in Protein - Part B CFB at Day 14 (Follow-up)	-0.1 g/L Standard Deviation 3.00	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Sodium - Part B Baseline	141.8 mmol/L Standard Deviation 1.97	—	—
CFB in Sodium - Part B CFB at Dose 4 (SAGE-217): Predose	0.1 mmol/L Standard Deviation 1.78	—	—
CFB in Sodium - Part B CFB at Dose 6 (SAGE-217): Predose	0.1 mmol/L Standard Deviation 1.46	—	—
CFB in Sodium - Part B CFB at Day 8 (Follow-up)	0.4 mmol/L Standard Deviation 2.21	—	—
CFB in Sodium - Part B CFB at Day 14 (Follow-up)	-0.1 mmol/L Standard Deviation 3.00	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Urate - Part B Baseline	0.291 mmol/L Standard Deviation 0.0748	—	—
CFB in Urate - Part B CFB at Dose 4 (SAGE-217): Predose	-0.001 mmol/L Standard Deviation 0.0252	—	—
CFB in Urate - Part B CFB at Dose 6 (SAGE-217): Predose	0.001 mmol/L Standard Deviation 0.0360	—	—
CFB in Urate - Part B CFB at Day 8 (Follow-up)	0.006 mmol/L Standard Deviation 0.0254	—	—
CFB in Urate - Part B CFB at Day 14 (Follow-up)	0.007 mmol/L Standard Deviation 0.0319	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Clinical chemistry measures included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, chloride, creatinine, lipase, magnesium, phosphate, potassium, protein, sodium, urate and urea nitrogen. Baseline is the last measurement taken before the first dose of the study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Urea Nitrogen - Part B Baseline	5.993 mmol/L Standard Deviation 1.7667	—	—
CFB in Urea Nitrogen - Part B CFB at Dose 4 (SAGE-217): Predose	2.142 mmol/L Standard Deviation 1.9554	—	—
CFB in Urea Nitrogen - Part B CFB at Dose 6 (SAGE-217): Predose	1.275 mmol/L Standard Deviation 1.7917	—	—
CFB in Urea Nitrogen - Part B CFB at Day 8 (Follow-up)	0.663 mmol/L Standard Deviation 1.9345	—	—
CFB in Urea Nitrogen - Part B CFB at Day 14 (Follow-up)	0.153 mmol/L Standard Deviation 1.2580	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Urinalysis measures included specific gravity and pH. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Specific Gravity - Part B Baseline	1.018 ratio Standard Deviation 0.0061	—	—
CFB in Specific Gravity - Part B CFB at Dose 4 (SAGE-217): Predose	0.003 ratio Standard Deviation 0.0038	—	—
CFB in Specific Gravity - Part B CFB at Dose 6 (SAGE-217): Predose	0.001 ratio Standard Deviation 0.0053	—	—
CFB in Specific Gravity - Part B CFB at Day 8 (Follow-up)	-0.004 ratio Standard Deviation 0.0077	—	—
CFB in Specific Gravity - Part B CFB at Day 14 (Follow-up)	0.000 ratio Standard Deviation 0.0063	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug. Number analyzed = Number of participants with data available at the specific time point.

Urinalysis measures included specific gravity and pH. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in pH - Part B Baseline	6.11 pH Standard Deviation 0.924	—	—
CFB in pH - Part B CFB at Dose 4 (SAGE-217): Predose	-0.18 pH Standard Deviation 1.103	—	—
CFB in pH - Part B CFB at Dose 6 (SAGE-217): Predose	-0.32 pH Standard Deviation 1.085	—	—
CFB in pH - Part B CFB at Day 8 (Follow-up)	0.39 pH Standard Deviation 0.984	—	—
CFB in pH - Part B CFB at Day 14 (Follow-up)	-0.12 pH Standard Deviation 0.820	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Temperature - Part B Baseline	36.56 degrees C Standard Deviation 0.306	—	—
CFB in Temperature - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-0.10 degrees C Standard Deviation 0.199	—	—
CFB in Temperature - Part B CFB at Dose 1 (SAGE-217): 2 Hours Postdose	0.01 degrees C Standard Deviation 0.316	—	—
CFB in Temperature - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-0.19 degrees C Standard Deviation 0.316	—	—
CFB in Temperature - Part B CFB at Dose 2 (SAGE-217): Predose	-0.23 degrees C Standard Deviation 0.370	—	—
CFB in Temperature - Part B CFB at Dose 2 (SAGE-217): 1 Hour Postdose	-0.15 degrees C Standard Deviation 0.375	—	—
CFB in Temperature - Part B CFB at Dose 2 (SAGE-217): 2 Hours Postdose	-0.03 degrees C Standard Deviation 0.310	—	—
CFB in Temperature - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-0.09 degrees C Standard Deviation 0.380	—	—
CFB in Temperature - Part B CFB at Dose 3 (SAGE-217): Predose	-0.06 degrees C Standard Deviation 0.485	—	—
CFB in Temperature - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.11 degrees C Standard Deviation 0.327	—	—
CFB in Temperature - Part B CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-0.15 degrees C Standard Deviation 0.282	—	—
CFB in Temperature - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-0.06 degrees C Standard Deviation 0.386	—	—
CFB in Temperature - Part B CFB at Dose 4 (SAGE-217): Predose	-0.10 degrees C Standard Deviation 0.451	—	—
CFB in Temperature - Part B CFB at Dose 4 (SAGE-217): 1 Hour Postdose	0.01 degrees C Standard Deviation 0.408	—	—
CFB in Temperature - Part B CFB at Dose 4 (SAGE-217): 2 Hours Postdose	-0.09 degrees C Standard Deviation 0.358	—	—
CFB in Temperature - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-0.12 degrees C Standard Deviation 0.336	—	—
CFB in Temperature - Part B CFB at Dose 5 (SAGE-217): Predose	-0.08 degrees C Standard Deviation 0.418	—	—
CFB in Temperature - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-0.08 degrees C Standard Deviation 0.423	—	—
CFB in Temperature - Part B CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-0.09 degrees C Standard Deviation 0.562	—	—
CFB in Temperature - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-0.09 degrees C Standard Deviation 0.512	—	—
CFB in Temperature - Part B CFB at Dose 6 (SAGE-217): Predose	0.01 degrees C Standard Deviation 0.240	—	—
CFB in Temperature - Part B CFB at Dose 6 (SAGE-217): 1 Hour Postdose	0.05 degrees C Standard Deviation 0.266	—	—
CFB in Temperature - Part B CFB at Dose 6 (SAGE-217): 2 Hours Postdose	-0.05 degrees C Standard Deviation 0.289	—	—
CFB in Temperature - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-0.07 degrees C Standard Deviation 0.363	—	—
CFB in Temperature - Part B CFB at Dose 7 (SAGE-217): Predose	-0.07 degrees C Standard Deviation 0.477	—	—
CFB in Temperature - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-0.10 degrees C Standard Deviation 0.348	—	—
CFB in Temperature - Part B CFB at Dose 7 (SAGE-217): 2 Hours Postdose	-0.08 degrees C Standard Deviation 0.352	—	—
CFB in Temperature - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-0.10 degrees C Standard Deviation 0.415	—	—
CFB in Temperature - Part B CFB at Day 14 (Follow-up)	-0.01 degrees C Standard Deviation 0.291	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Heart Rate - Part B Baseline	72.9 beats/min Standard Deviation 9.25	—	—
CFB in Heart Rate - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	0.1 beats/min Standard Deviation 7.82	—	—
CFB in Heart Rate - Part B CFB at Dose 1 (SAGE-217): 2 Hours Postdose	0.1 beats/min Standard Deviation 7.78	—	—
CFB in Heart Rate - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-3.6 beats/min Standard Deviation 15.35	—	—
CFB in Heart Rate - Part B CFB at Dose 2 (SAGE-217): Predose	-1.6 beats/min Standard Deviation 7.14	—	—
CFB in Heart Rate - Part B CFB at Dose 2 (SAGE-217): 1 Hour Postdose	0.4 beats/min Standard Deviation 12.44	—	—
CFB in Heart Rate - Part B CFB at Dose 2 (SAGE-217): 2 Hours Postdose	2.5 beats/min Standard Deviation 11.94	—	—
CFB in Heart Rate - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-3.0 beats/min Standard Deviation 11.08	—	—
CFB in Heart Rate - Part B CFB at Dose 3 (SAGE-217): Predose	0.3 beats/min Standard Deviation 9.02	—	—
CFB in Heart Rate - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.1 beats/min Standard Deviation 7.67	—	—
CFB in Heart Rate - Part B CFB at Dose 3 (SAGE-217): 2 Hours Postdose	3.1 beats/min Standard Deviation 7.95	—	—
CFB in Heart Rate - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-0.1 beats/min Standard Deviation 10.36	—	—
CFB in Heart Rate - Part B CFB at Dose 4 (SAGE-217): Predose	2.5 beats/min Standard Deviation 8.16	—	—
CFB in Heart Rate - Part B CFB at Dose 4 (SAGE-217): 1 Hour Postdose	1.4 beats/min Standard Deviation 9.41	—	—
CFB in Heart Rate - Part B CFB at Dose 4 (SAGE-217): 2 Hours Postdose	1.4 beats/min Standard Deviation 8.31	—	—
CFB in Heart Rate - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-1.6 beats/min Standard Deviation 9.65	—	—
CFB in Heart Rate - Part B CFB at Dose 5 (SAGE-217): Predose	2.5 beats/min Standard Deviation 8.97	—	—
CFB in Heart Rate - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	1.9 beats/min Standard Deviation 10.61	—	—
CFB in Heart Rate - Part B CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-0.4 beats/min Standard Deviation 9.08	—	—
CFB in Heart Rate - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-4.1 beats/min Standard Deviation 9.12	—	—
CFB in Heart Rate - Part B CFB at Dose 6 (SAGE-217): Predose	2.1 beats/min Standard Deviation 8.61	—	—
CFB in Heart Rate - Part B CFB at Dose 6 (SAGE-217): 1 Hour Postdose	1.6 beats/min Standard Deviation 7.08	—	—
CFB in Heart Rate - Part B CFB at Dose 6 (SAGE-217): 2 Hours Postdose	1.2 beats/min Standard Deviation 6.13	—	—
CFB in Heart Rate - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	2.4 beats/min Standard Deviation 11.29	—	—
CFB in Heart Rate - Part B CFB at Dose 7 (SAGE-217): Predose	-1.7 beats/min Standard Deviation 8.42	—	—
CFB in Heart Rate - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-1.7 beats/min Standard Deviation 8.76	—	—
CFB in Heart Rate - Part B CFB at Dose 7 (SAGE-217): 2 Hours Postdose	0.9 beats/min Standard Deviation 8.93	—	—
CFB in Heart Rate - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-1.3 beats/min Standard Deviation 6.83	—	—
CFB in Heart Rate - Part B CFB at Day 14 (Follow-up)	-5.0 beats/min Standard Deviation 8.34	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Respiratory Rate - Part B Baseline	15.6 breaths/min Standard Deviation 1.91	—	—
CFB in Respiratory Rate - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	0.6 breaths/min Standard Deviation 1.99	—	—
CFB in Respiratory Rate - Part B CFB at Dose 1 (SAGE-217): 2 Hours Postdose	0.6 breaths/min Standard Deviation 1.98	—	—
CFB in Respiratory Rate - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.8 breaths/min Standard Deviation 1.31	—	—
CFB in Respiratory Rate - Part B CFB at Dose 2 (SAGE-217): Predose	-0.9 breaths/min Standard Deviation 2.07	—	—
CFB in Respiratory Rate - Part B CFB at Dose 2 (SAGE-217): 1 Hour Postdose	-0.9 breaths/min Standard Deviation 2.09	—	—
CFB in Respiratory Rate - Part B CFB at Dose 2 (SAGE-217): 2 Hours Postdose	0.4 breaths/min Standard Deviation 1.50	—	—
CFB in Respiratory Rate - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	0.8 breaths/min Standard Deviation 1.58	—	—
CFB in Respiratory Rate - Part B CFB at Dose 3 (SAGE-217): Predose	0.5 breaths/min Standard Deviation 1.79	—	—
CFB in Respiratory Rate - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.4 breaths/min Standard Deviation 1.74	—	—
CFB in Respiratory Rate - Part B CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-0.6 breaths/min Standard Deviation 2.03	—	—
CFB in Respiratory Rate - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	0.6 breaths/min Standard Deviation 1.50	—	—
CFB in Respiratory Rate - Part B CFB at Dose 4 (SAGE-217): Predose	-0.2 breaths/min Standard Deviation 2.36	—	—
CFB in Respiratory Rate - Part B CFB at Dose 4 (SAGE-217): 1 Hour Postdose	-0.4 breaths/min Standard Deviation 1.55	—	—
CFB in Respiratory Rate - Part B CFB at Dose 4 (SAGE-217): 2 Hours Postdose	-0.3 breaths/min Standard Deviation 1.86	—	—
CFB in Respiratory Rate - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	1.4 breaths/min Standard Deviation 1.87	—	—
CFB in Respiratory Rate - Part B CFB at Dose 5 (SAGE-217): Predose	0.4 breaths/min Standard Deviation 1.45	—	—
CFB in Respiratory Rate - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	1.4 breaths/min Standard Deviation 1.98	—	—
CFB in Respiratory Rate - Part B CFB at Dose 5 (SAGE-217): 2 Hours Postdose	0.6 breaths/min Standard Deviation 2.38	—	—
CFB in Respiratory Rate - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	0.4 breaths/min Standard Deviation 1.79	—	—
CFB in Respiratory Rate - Part B CFB at Dose 6 (SAGE-217): Predose	0.4 breaths/min Standard Deviation 1.74	—	—
CFB in Respiratory Rate - Part B CFB at Dose 6 (SAGE-217): 1 Hour Postdose	-0.1 breaths/min Standard Deviation 1.64	—	—
CFB in Respiratory Rate - Part B CFB at Dose 6 (SAGE-217): 2 Hours Postdose	0.5 breaths/min Standard Deviation 1.99	—	—
CFB in Respiratory Rate - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	0.4 breaths/min Standard Deviation 1.78	—	—
CFB in Respiratory Rate - Part B CFB at Dose 7 (SAGE-217): Predose	-1.1 breaths/min Standard Deviation 2.02	—	—
CFB in Respiratory Rate - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	1.6 breaths/min Standard Deviation 1.39	—	—
CFB in Respiratory Rate - Part B CFB at Dose 7 (SAGE-217): 2 Hours Postdose	-0.7 breaths/min Standard Deviation 2.40	—	—
CFB in Respiratory Rate - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	0.6 breaths/min Standard Deviation 1.65	—	—
CFB in Respiratory Rate - Part B CFB at Day 14 (Follow-up)	0.3 breaths/min Standard Deviation 1.90	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Supine Systolic Blood Pressure - Part B Baseline	131.7 mmHg Standard Deviation 16.50	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-1.7 mmHg Standard Deviation 9.15	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 2 Hours Postdose	-1.4 mmHg Standard Deviation 7.60	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.3 mmHg Standard Deviation 13.81	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): Predose	-3.3 mmHg Standard Deviation 18.20	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 1 Hour Postdose	2.9 mmHg Standard Deviation 14.61	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 2 Hours Postdose	0.1 mmHg Standard Deviation 16.11	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	6.1 mmHg Standard Deviation 18.57	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): Predose	-1.2 mmHg Standard Deviation 12.35	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.1 mmHg Standard Deviation 10.64	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-1.6 mmHg Standard Deviation 13.21	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-1.1 mmHg Standard Deviation 22.03	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): Predose	-1.4 mmHg Standard Deviation 16.26	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 1 Hour Postdose	-1.1 mmHg Standard Deviation 14.22	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 2 Hours Postdose	-4.3 mmHg Standard Deviation 14.21	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	1.2 mmHg Standard Deviation 18.07	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): Predose	-5.7 mmHg Standard Deviation 14.67	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-4.0 mmHg Standard Deviation 15.54	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-3.6 mmHg Standard Deviation 18.79	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	2.3 mmHg Standard Deviation 11.82	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): Predose	-10.9 mmHg Standard Deviation 17.18	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 1 Hour Postdose	-6.5 mmHg Standard Deviation 18.68	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 2 Hours Postdose	-2.8 mmHg Standard Deviation 18.48	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-4.1 mmHg Standard Deviation 15.90	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): Predose	-1.7 mmHg Standard Deviation 12.63	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	2.4 mmHg Standard Deviation 12.33	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 2 Hours Postdose	2.5 mmHg Standard Deviation 11.94	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-1.2 mmHg Standard Deviation 13.98	—	—
CFB in Supine Systolic Blood Pressure - Part B CFB at Day 14 (Follow-up)	3.4 mmHg Standard Deviation 15.55	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Standing Systolic Blood Pressure - Part B Baseline	127.8 mmHg Standard Deviation 14.89	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-2.9 mmHg Standard Deviation 10.51	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 2 Hours Postdose	-2.4 mmHg Standard Deviation 8.41	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.6 mmHg Standard Deviation 7.68	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): Predose	-3.4 mmHg Standard Deviation 15.96	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 1 Hour Postdose	-1.5 mmHg Standard Deviation 14.03	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 2 Hours Postdose	1.7 mmHg Standard Deviation 15.49	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-0.8 mmHg Standard Deviation 13.50	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): Predose	-4.2 mmHg Standard Deviation 11.77	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.8 mmHg Standard Deviation 11.56	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-4.4 mmHg Standard Deviation 11.21	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	0.0 mmHg Standard Deviation 17.29	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): Predose	-4.5 mmHg Standard Deviation 12.68	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 1 Hour Postdose	-4.1 mmHg Standard Deviation 18.50	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 2 Hours Postdose	-5.5 mmHg Standard Deviation 11.25	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-3.8 mmHg Standard Deviation 13.38	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): Predose	-7.5 mmHg Standard Deviation 8.26	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-3.9 mmHg Standard Deviation 12.07	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-5.6 mmHg Standard Deviation 14.59	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-2.3 mmHg Standard Deviation 10.01	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): Predose	-9.4 mmHg Standard Deviation 8.80	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 1 Hour Postdose	-6.6 mmHg Standard Deviation 11.05	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 2 Hours Postdose	-4.7 mmHg Standard Deviation 10.25	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-8.6 mmHg Standard Deviation 11.05	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): Predose	-1.2 mmHg Standard Deviation 9.01	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	1.4 mmHg Standard Deviation 10.60	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 2 Hours Postdose	3.5 mmHg Standard Deviation 13.18	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-7.5 mmHg Standard Deviation 12.79	—	—
CFB in Standing Systolic Blood Pressure - Part B CFB at Day 14 (Follow-up)	0.7 mmHg Standard Deviation 14.50	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Supine Diastolic Blood Pressure - Part B Baseline	78.2 mmHg Standard Deviation 7.49	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	0.7 mmHg Standard Deviation 7.13	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 2 Hours Postdose	1.6 mmHg Standard Deviation 7.20	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.6 mmHg Standard Deviation 7.23	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): Predose	-0.1 mmHg Standard Deviation 10.00	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 1 Hour Postdose	1.9 mmHg Standard Deviation 9.23	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 2 Hours Postdose	-0.5 mmHg Standard Deviation 9.75	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	1.9 mmHg Standard Deviation 9.07	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): Predose	0.1 mmHg Standard Deviation 8.54	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-1.4 mmHg Standard Deviation 7.39	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-0.9 mmHg Standard Deviation 12.21	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	0.6 mmHg Standard Deviation 11.15	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): Predose	-0.3 mmHg Standard Deviation 9.24	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 1 Hour Postdose	1.5 mmHg Standard Deviation 8.29	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 2 Hours Postdose	0.3 mmHg Standard Deviation 8.18	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	0.4 mmHg Standard Deviation 9.76	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): Predose	-1.1 mmHg Standard Deviation 9.05	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-0.7 mmHg Standard Deviation 9.92	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-0.6 mmHg Standard Deviation 9.44	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-0.6 mmHg Standard Deviation 9.00	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): Predose	-2.4 mmHg Standard Deviation 9.24	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 1 Hour Postdose	1.1 mmHg Standard Deviation 9.49	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 2 Hours Postdose	0.6 mmHg Standard Deviation 9.15	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	1.9 mmHg Standard Deviation 9.74	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): Predose	-0.6 mmHg Standard Deviation 9.16	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	1.8 mmHg Standard Deviation 10.50	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 2 Hours Postdose	0.2 mmHg Standard Deviation 8.50	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	0.4 mmHg Standard Deviation 8.93	—	—
CFB in Supine Diastolic Blood Pressure - Part B CFB at Day 14 (Follow-up)	0.3 mmHg Standard Deviation 8.30	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Standing Diastolic Blood Pressure - Part B Baseline	81.9 mmHg Standard Deviation 6.99	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-2.0 mmHg Standard Deviation 6.04	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 2 Hours Postdose	-2.4 mmHg Standard Deviation 6.32	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-1.6 mmHg Standard Deviation 7.17	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): Predose	-3.9 mmHg Standard Deviation 7.18	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 1 Hour Postdose	-2.4 mmHg Standard Deviation 5.11	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 2 Hours Postdose	-1.5 mmHg Standard Deviation 7.69	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-1.9 mmHg Standard Deviation 8.64	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): Predose	-3.9 mmHg Standard Deviation 8.60	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-1.4 mmHg Standard Deviation 9.08	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-1.1 mmHg Standard Deviation 7.44	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-2.4 mmHg Standard Deviation 7.79	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): Predose	-2.4 mmHg Standard Deviation 7.53	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 1 Hour Postdose	-4.1 mmHg Standard Deviation 9.77	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 2 Hours Postdose	-2.9 mmHg Standard Deviation 8.69	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-2.8 mmHg Standard Deviation 9.18	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): Predose	-5.5 mmHg Standard Deviation 8.93	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-1.4 mmHg Standard Deviation 7.91	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-3.1 mmHg Standard Deviation 8.51	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	0.0 mmHg Standard Deviation 10.03	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): Predose	-4.0 mmHg Standard Deviation 7.74	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 1 Hour Postdose	-1.6 mmHg Standard Deviation 8.35	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 2 Hours Postdose	-2.0 mmHg Standard Deviation 7.65	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-2.1 mmHg Standard Deviation 8.27	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): Predose	-1.7 mmHg Standard Deviation 9.21	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-0.2 mmHg Standard Deviation 8.86	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 2 Hours Postdose	0.6 mmHg Standard Deviation 8.14	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-2.7 mmHg Standard Deviation 8.59	—	—
CFB in Standing Diastolic Blood Pressure - Part B CFB at Day 14 (Follow-up)	-1.1 mmHg Standard Deviation 9.21	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

Vital sign measures included temperature, heart rate, respiratory rate, supine systolic blood pressure, standing systolic blood pressure, supine diastolic blood pressure, standing diastolic blood pressure and pulse oximetry. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Pulse Oximetry - Part B Baseline	96.9 percentage Standard Deviation 1.51	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-0.6 percentage Standard Deviation 1.60	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 1 (SAGE-217): 2 Hours Postdose	0.0 percentage Standard Deviation 2.08	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.4 percentage Standard Deviation 1.86	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 2 (SAGE-217): Predose	-0.3 percentage Standard Deviation 1.77	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 2 (SAGE-217): 1 Hour Postdose	0.1 percentage Standard Deviation 1.64	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 2 (SAGE-217): 2 Hours Postdose	0.1 percentage Standard Deviation 1.73	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 2 (SAGE-217): 12 Hours Postdose	0.3 percentage Standard Deviation 1.38	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 3 (SAGE-217): Predose	0.1 percentage Standard Deviation 1.51	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	0.3 percentage Standard Deviation 2.02	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-0.5 percentage Standard Deviation 1.87	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	0.0 percentage Standard Deviation 2.15	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 4 (SAGE-217): Predose	-0.6 percentage Standard Deviation 1.69	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 4 (SAGE-217): 1 Hour Postdose	0.6 percentage Standard Deviation 1.01	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 4 (SAGE-217): 2 Hours Postdose	0.1 percentage Standard Deviation 1.46	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-0.3 percentage Standard Deviation 2.09	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 5 (SAGE-217): Predose	0.5 percentage Standard Deviation 1.34	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	0.6 percentage Standard Deviation 1.91	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 5 (SAGE-217): 2 Hours Postdose	0.0 percentage Standard Deviation 1.66	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	0.4 percentage Standard Deviation 1.55	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 6 (SAGE-217): Predose	-0.2 percentage Standard Deviation 1.63	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 6 (SAGE-217): 1 Hour Postdose	0.1 percentage Standard Deviation 1.33	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 6 (SAGE-217): 2 Hours Postdose	0.1 percentage Standard Deviation 1.33	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 6 (SAGE-217): 12 Hours Postdose	0.3 percentage Standard Deviation 1.64	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 7 (SAGE-217): Predose	0.2 percentage Standard Deviation 1.25	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-0.4 percentage Standard Deviation 1.65	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 7 (SAGE-217): 2 Hours Postdose	0.0 percentage Standard Deviation 1.71	—	—
CFB in Pulse Oximetry - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	0.1 percentage Standard Deviation 1.79	—	—
CFB in Pulse Oximetry - Part B CFB at Day 14 (Follow-up)	0.5 percentage Standard Deviation 1.91	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in ECG Mean Heart Rate - Part B Baseline	71.4 beats/min Standard Deviation 10.24	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	0.1 beats/min Standard Deviation 5.55	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-6.6 beats/min Standard Deviation 7.81	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 3 (SAGE-217): Predose	0.2 beats/min Standard Deviation 6.19	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.3 beats/min Standard Deviation 5.03	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-1.6 beats/min Standard Deviation 9.88	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 5 (SAGE-217): Predose	2.2 beats/min Standard Deviation 6.28	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	1.8 beats/min Standard Deviation 7.82	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-2.4 beats/min Standard Deviation 9.39	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 7 (SAGE-217): Predose	0.2 beats/min Standard Deviation 6.81	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-0.7 beats/min Standard Deviation 6.97	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	1.4 beats/min Standard Deviation 6.35	—	—
CFB in ECG Mean Heart Rate - Part B CFB at Day 14 (Follow-up)	-6.1 beats/min Standard Deviation 8.57	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aggregate PR Interval - Part B Baseline	174.0 msec Interval 141.0 to 203.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	2.5 msec Interval -20.0 to 96.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.0 msec Interval -24.0 to 17.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 3 (SAGE-217): Predose	-2.0 msec Interval -29.0 to 8.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-1.5 msec Interval -33.0 to 8.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	3.5 msec Interval -27.0 to 20.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 5 (SAGE-217): Predose	1.5 msec Interval -28.0 to 46.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	2.0 msec Interval -19.0 to 12.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-1.5 msec Interval -22.0 to 22.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 7 (SAGE-217): Predose	-2.0 msec Interval -17.0 to 18.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	0.0 msec Interval -36.0 to 10.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-1.5 msec Interval -26.0 to 27.0	—	—
CFB in Aggregate PR Interval - Part B CFB at Day 14 (Follow-up)	-2.5 msec Interval -31.0 to 7.0	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aggregate RR Interval - Part B Baseline	823.0 msec Interval 683.0 to 1239.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-19.0 msec Interval -93.0 to 142.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	67.5 msec Interval -68.0 to 366.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 3 (SAGE-217): Predose	-32.5 msec Interval -85.0 to 141.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-10.0 msec Interval -140.0 to 143.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	7.0 msec Interval -164.0 to 231.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 5 (SAGE-217): Predose	-23.5 msec Interval -132.0 to 99.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-24.5 msec Interval -148.0 to 96.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	50.0 msec Interval -185.0 to 304.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 7 (SAGE-217): Predose	-16.0 msec Interval -80.0 to 212.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-26.0 msec Interval -76.0 to 180.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	16.5 msec Interval -148.0 to 74.0	—	—
CFB in Aggregate RR Interval - Part B CFB at Day 14 (Follow-up)	66.0 msec Interval -76.0 to 397.0	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aggregate QT Interval - Part B Baseline	374.0 msec Interval 361.0 to 442.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	3.5 msec Interval -41.0 to 36.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	10.0 msec Interval -20.0 to 70.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 3 (SAGE-217): Predose	2.0 msec Interval -21.0 to 32.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	3.5 msec Interval -34.0 to 31.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	0.0 msec Interval -52.0 to 31.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 5 (SAGE-217): Predose	-1.0 msec Interval -35.0 to 17.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-5.5 msec Interval -37.0 to 25.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	11.0 msec Interval -45.0 to 41.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 7 (SAGE-217): Predose	-5.0 msec Interval -23.0 to 21.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	3.5 msec Interval -32.0 to 32.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	2.5 msec Interval -30.0 to 21.0	—	—
CFB in Aggregate QT Interval - Part B CFB at Day 14 (Follow-up)	14.0 msec Interval -19.0 to 57.0	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aggregate QRS Duration - Part B Baseline	99.5 msec Interval 76.0 to 153.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	0.0 msec Interval -9.0 to 12.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-1.0 msec Interval -8.0 to 16.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 3 (SAGE-217): Predose	-1.5 msec Interval -11.0 to 9.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	0.0 msec Interval -12.0 to 10.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-0.5 msec Interval -14.0 to 6.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 5 (SAGE-217): Predose	-1.5 msec Interval -10.0 to 16.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	1.5 msec Interval -5.0 to 11.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-3.5 msec Interval -12.0 to 6.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 7 (SAGE-217): Predose	-0.5 msec Interval -5.0 to 238.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-1.0 msec Interval -10.0 to 6.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-1.0 msec Interval -11.0 to 6.0	—	—
CFB in Aggregate QRS Duration - Part B CFB at Day 14 (Follow-up)	0.5 msec Interval -11.0 to 11.0	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

ECG measures included ECG mean heart rate, aggregate PR interval, aggregate RR interval, aggregate QT interval, aggregate QRS duration and aggregate QTcF interval. Baseline is the last measurement taken before the first dose of study drug. Doses 1 to 7 were given on Days 1 to 7, respectively. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
CFB in Aggregate QTcF Interval - Part B Baseline	407.0 msec Interval 384.0 to 432.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 1 (SAGE-217): 1 Hour Postdose	3.0 msec Interval -35.0 to 54.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-2.5 msec Interval -34.0 to 60.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 3 (SAGE-217): Predose	0.0 msec Interval -11.0 to 28.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 3 (SAGE-217): 1 Hour Postdose	0.5 msec Interval -18.0 to 29.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-1.5 msec Interval -37.0 to 12.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 5 (SAGE-217): Predose	1.0 msec Interval -19.0 to 19.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 5 (SAGE-217): 1 Hour Postdose	0.0 msec Interval -19.0 to 22.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 5 (SAGE-217): 12 Hours Postdose	5.5 msec Interval -27.0 to 17.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 7 (SAGE-217): Predose	-1.0 msec Interval -16.0 to 29.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-2.0 msec Interval -25.0 to 20.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Dose 7 (SAGE-217): 12 Hours Postdose	2.0 msec Interval -11.0 to 17.0	—	—
CFB in Aggregate QTcF Interval - Part B CFB at Day 14 (Follow-up)	0.5 msec Interval -10.0 to 21.0	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 14

Population: The safety population included all participants who were administered study drug.

The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included "yes" or "no"' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with a specific plan. The C-SSRS SB items involved actual attempt, interrupted attempt, aborted attempt, preparatory acts or behavior, suicidal behavior and suicide. The analysis was performed in participants included in Part B of the study.

Outcome measures

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=14 Participants Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
Percentage of Participants With a Response of 'Yes' to Any C-SSRS Suicidal Ideation or Suicidal Behavior Item - Part B Suicidal Ideation: Wish to be Dead: Pre-treatment	14.3 percentage of participants	—	—
Percentage of Participants With a Response of 'Yes' to Any C-SSRS Suicidal Ideation or Suicidal Behavior Item - Part B Suicidal Ideation: Wish to be Dead: Post-treatment	0 percentage of participants	—	—
Percentage of Participants With a Response of 'Yes' to Any C-SSRS Suicidal Ideation or Suicidal Behavior Item - Part B Suicidal Behavior: Pre-treatment	0 percentage of participants	—	—
Percentage of Participants With a Response of 'Yes' to Any C-SSRS Suicidal Ideation or Suicidal Behavior Item - Part B Suicidal Behavior: Post-treatment	0 percentage of participants	—	—

Adverse Events

Part A: Antiparkinsonian Agent(s) Day 1 to Day 3

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part A: SAGE-217 Day 4 to Day 7

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Part A: Follow-up

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part B: SAGE-217 Dose 1 to Dose 7

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Part B: Follow-up

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3 n=15 participants at risk Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	Part A: SAGE-217 Day 4 to Day 7 n=14 participants at risk Participants received SAGE-217 at a dose of 30 mg per day, oral solution, for Days 4 to 7 in the morning with food. If the initial dose was not tolerated, doses could be reduced to 10 or 20 mg per day.	Part A: Follow-up n=15 participants at risk Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.	Part B: SAGE-217 Dose 1 to Dose 7 n=14 participants at risk Participants on a stable dose of antiparkinsonian agent(s) received SAGE-217, up to 30 mg per day, capsules, for Days 1 to 7 in the evening with food.	Part B: Follow-up n=14 participants at risk Participants received antiparkinsonian agent(s) at normally prescribed dosing schedule for Days 8 to 14.
Nervous system disorders Sedation	6.7% 1/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	71.4% 10/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	14.3% 2/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Somnolence	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	42.9% 6/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	14.3% 2/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Dizziness	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	28.6% 4/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	14.3% 2/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Myoclonus	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	21.4% 3/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Headache	6.7% 1/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Amnesia	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Cognitive Disorder	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Dyskinesia	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Migraine	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Migraine with Aura	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Tremor	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Nervous system disorders Parkinson's Disease	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Gastrointestinal disorders Nausea	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	21.4% 3/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Gastrointestinal disorders Abdominal Distension	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Gastrointestinal disorders Diarrhoea	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	6.7% 1/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Gastrointestinal disorders Dyspepsia	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Gastrointestinal disorders Faeces soft	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Gastrointestinal disorders Flatulence	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Gastrointestinal disorders Haematochezia	6.7% 1/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Gastrointestinal disorders Vomiting	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	6.7% 1/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Gastrointestinal disorders Salivary Hypersecretion	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
General disorders Feeling drunk	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	28.6% 4/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Vascular disorders Orthostatic Hypotension	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	14.3% 2/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Vascular disorders Hypotension	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Eye disorders Photophobia	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Investigations Lipase Increased	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	6.7% 1/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Musculoskeletal and connective tissue disorders Pain in Extremity	6.7% 1/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Musculoskeletal and connective tissue disorders Limb Discomfort	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Psychiatric disorders Panic Attack	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Psychiatric disorders Anxiety	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Psychiatric disorders Confusional State	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.
Skin and subcutaneous tissue disorders Dermatitis Contact	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	7.1% 1/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/15 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.	0.00% 0/14 • Part A: Up to 14 days; Part B: Up to 14 days The safety population included all participants who were administered study drug \[SAGE-217 or levodopa (Part A); or SAGE-217 or antiparkinsonian agent(s) (Part B)\]. Number of participants at risk is number of participants in the safety population that remained in the study during each period.

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 non-commercial 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