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

• Sponsor: Sage Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03000569
• Collaborator: (none)
• Enrollment: 29
• Locations: 11
• Arms: 2
• Actual Duration (Months): 9.4
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study assesses the safety, tolerability, pharmacokinetics and efficacy of SAGE-217 in 29 participants with moderate to severe Parkinson's Disease.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Drug: SAGE-217; Drug: Levodopa; Drug: Antiparkinsonian Agent(s)	Phase 2

Detailed Description

Part A of the study is an open-label design with dosing of Levodopa for 3 days followed by SAGE-217 for 4 days.

Part B of the study is an open-label design with evening dosing of SAGE-217 for 7 days as an adjunct to antiparkinsonian agent(s).

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Two-Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of SAGE-217 in Subjects With Parkinson's Disease
• Actual Study Start Date: Nov 30, 2016
• Actual Primary Completion Date: Sep 11, 2017
• Actual Study Completion Date: Sep 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: SAGE-217; Drug: Levodopa; Levodopa (including carbidopa-levodopa) administered as antiparkinsonian agent(s).
Experimental: 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.	Drug: SAGE-217; Drug: Antiparkinsonian Agent(s); Antiparkinsonian agent(s) were administered as a clinical practice as standard of care, which includes levodopa (i.e. levodopa/carbidopa) or dopamine agonists or catechol-O-methyltransferase (COMT) inhibitors or monoamine oxidase (BMAO-B) inhibitors.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) - Part A [Day 1 to Day 14]

   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.

2. Percentage of Participants With TEAEs, Graded by Severity - Part A [Day 1 to Day 14]

   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.

3. Change From Baseline (CFB) in Basophils - Part A [Day 1 to Day 14]

   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.

4. CFB in Basophils to Leukocytes Ratio [Percentage (%)] - Part A [Day 1 to Day 14]

   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 (%).

5. CFB in Eosinophils - Part A [Day 1 to Day 14]

   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.

6. CFB in Eosinophils to Leukocytes Ratio (%) - Part A [Day 1 to Day 14]

   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 (%).

7. CFB in Erythrocytes - Part A [Day 1 to Day 14]

   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.

8. CFB in Hematocrit - Part A [Day 1 to Day 14]

   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.

9. CFB in Hemoglobin - Part A [Day 1 to Day 14]

   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.

10. CFB in Leukocytes - Part A [Day 1 to Day 14]

    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.

11. CFB in Lymphocytes - Part A [Day 1 to Day 14]

    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.

12. CFB in Lymphocytes to Leukocytes Ratio (%) - Part A [Day 1 to Day 14]

    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 (%).

13. CFB in Monocytes - Part A [Day 1 to Day 14]

    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.

14. CFB in Monocytes to Leukocytes Ratio (%) - Part A [Day 1 to Day 14]

    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 (%).

15. CFB in Neutrophils- Part A [Day 1 to Day 14]

    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.

16. CFB in Neutrophils to Leukocytes Ratio (%) - Part A [Day 1 to Day 14]

    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 (%).

17. CFB in Platelets - Part A [Day 1 to Day 14]

    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.

18. CFB in Reticulocytes - Part A [Day 1 to Day 14]

    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.

19. CFB in Reticulocytes to Erythrocytes Ratio (%) - Part A [Day 1 to Day 14]

    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 (%).

20. CFB in Activated Partial Thromboplastin Time - Part A [Day 1 to Day 14]

    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.

21. CFB in Prothrombin International Normalized Ratio - Part A [Day 1 to Day 14]

    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.

22. CFB in Prothrombin Time - Part A [Day 1 to Day 14]

    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.

23. CFB in Alanine Aminotransferase - Part A [Day 1 to Day 14]

    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.

24. CFB in Albumin - Part A [Day 1 to Day 14]

    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.

25. CFB in Alkaline Phosphatase - Part A [Day 1 to Day 14]

    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.

26. CFB in Aspartate Aminotransferase - Part A [Day 1 to Day 14]

    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.

27. CFB in Bicarbonate - Part A [Day 1 to Day 14]

    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.

28. CFB in Bilirubin - Part A [Day 1 to Day 14]

    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.

29. CFB in Calcium - Part A [Day 1 to Day 14]

    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.

30. CFB in Chloride - Part A [Day 1 to Day 14]

    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.

31. CFB in Creatinine - Part A [Day 1 to Day 14]

    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.

32. CFB in Lipase - Part A [Day 1 to Day 14]

    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.

33. CFB in Magnesium - Part A [Day 1 to Day 14]

    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.

34. CFB in Phosphate - Part A [Day 1 to Day 14]

    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.

35. CFB in Potassium - Part A [Day 1 to Day 14]

    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.

36. CFB in Protein - Part A [Day 1 to Day 14]

    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.

37. CFB in Sodium - Part A [Day 1 to Day 14]

    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.

38. CFB in Urate - Part A [Day 1 to Day 14]

    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.

39. CFB in Urea Nitrogen - Part A [Day 1 to Day 14]

    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.

40. CFB in Specific Gravity - Part A [Day 1 to Day 14]

    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.

41. CFB in pH - Part A [Day 1 to Day 14]

    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.

42. CFB in Temperature - Part A [Day 1 to Day 14]

    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.

43. CFB in Heart Rate - Part A [Day 1 to Day 14]

    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.

44. CFB in Respiratory Rate - Part A [Day 1 to Day 14]

    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.

45. CFB in Supine Systolic Blood Pressure - Part A [Day 1 to Day 14]

    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.

46. CFB in Standing Systolic Blood Pressure - Part A [Day 1 to Day 14]

    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.

47. CFB in Supine Diastolic Blood Pressure - Part A [Day 1 to Day 14]

    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.

48. CFB in Standing Diastolic Blood Pressure - Part A [Day 1 to Day 14]

    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.

49. CFB in Pulse Oximetry- Part A [Day 1 to Day 14]

    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.

50. CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A [Day 1 to Day 14]

    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.

51. CFB in Aggregate PR Interval - Part A [Day 1 to Day 14]

    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.

52. CFB in Aggregate RR Interval - Part A [Day 1 to Day 14]

    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.

53. CFB in Aggregate QT Interval - Part A [Day 1 to Day 14]

    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.

54. CFB in Aggregate QRS Duration - Part A [Day 1 to Day 14]

    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.

55. CFB in Aggregate QTcF Interval - Part A [Day 1 to Day 14]

    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.

56. CFB in Stanford Sleepiness Scale (SSS) Score - Part A [Day 1 to Day 14]

    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.

57. 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 [Day 1 to Day 14]

    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.

58. CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B [Baseline, Days 1 to 6 (12 and 23 hours postdose), Day 7 (12 hours postdose), Day 14]

    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.

Secondary Outcome Measures

1. MDS-UPDRS Part III Total Score - Part A [Days 1 to 7 (2, 4, 8, and 12 hours postdose), Day 8 and Day 14]

   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.

2. CFB in the MDS-UPDRS Part III Total Score - Part B [Baseline, Days 1 to 6 (12 and 23 hours postdose), Day 7 (12 hours postdose), Day 14]

   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.

3. CFB in the MDS-UPDRS Part I Total Score - Part B [Baseline, Day 7 (12 hours postdose), Day 14]

   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.

4. CFB in the MDS-UPDRS Part II Total Score - Part B [Baseline, Days 1 to 6 (12 and 23 hours postdose), Day 7 (12 hours postdose), Day 14]

   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.

5. CFB in the MDS-UPDRS Part I-IV Total Score - Part B [Baseline, Day 7 (12 hours postdose), Day 14]

   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.

6. Percentage of Participants With TEAEs - Part B [Day 1 to Day 14]

   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.

7. Percentage of Participants With TEAEs, Graded by Severity - Part B [Day 1 to Day 14]

   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.

8. CFB in Basophils - Part B [Day 1 to Day 14]

   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.

9. CFB in Basophils to Leukocytes Ratio (%) - Part B [Day 1 to Day 14]

   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 (%).

10. CFB in Eosinophils - Part B [Day 1 to Day 14]

    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.

11. CFB in Eosinophils to Leukocytes Ratio (%) - Part B [Day 1 to Day 14]

    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 (%).

12. CFB in Erythrocytes - Part B [Day 1 to Day 14]

    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.

13. CFB in Hematocrit - Part B [Day 1 to Day 14]

    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.

14. CFB in Hemoglobin - Part B [Day 1 to Day 14]

    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.

15. CFB in Leukocytes - Part B [Day 1 to Day 14]

    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.

16. CFB in Lymphocytes - Part B [Day 1 to Day 14]

    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.

17. CFB in Lymphocytes to Leukocytes Ratio (%) - Part B [Day 1 to Day 14]

    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 (%).

18. CFB in Monocytes - Part B [Day 1 to Day 14]

    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.

19. CFB in Monocytes to Leukocytes Ratio (%) - Part B [Day 1 to Day 14]

    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 (%).

20. CFB in Neutrophils - Part B [Day 1 to Day 14]

    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.

21. CFB in Neutrophils to Leukocytes Ratio (%) - Part B [Day 1 to Day 14]

    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 (%).

22. CFB in Platelets - Part B [Day 1 to Day 14]

    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.

23. CFB in Reticulocytes - Part B [Day 1 to Day 14]

    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.

24. CFB in Reticulocytes to Erythrocytes Ratio (%) - Part B [Day 1 to Day 14]

    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 (%).

25. CFB in Activated Partial Thromboplastin Time - Part B [Day 1 to Day 14]

    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.

26. CFB in Prothrombin International Normalized Ratio - Part B [Day 1 to Day 14]

    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.

27. CFB in Prothrombin Time - Part B [Day 1 to Day 14]

    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.

28. CFB in Alanine Aminotransferase - Part B [Day 1 to Day 14]

    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.

29. CFB in Albumin - Part B [Day 1 to Day 14]

    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.

30. CFB in Alkaline Phosphatase - Part B [Day 1 to Day 14]

    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.

31. CFB in Aspartate Aminotransferase - Part B [Day 1 to Day 14]

    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.

32. CFB in Bicarbonate - Part B [Day 1 to Day 14]

    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.

33. CFB in Bilirubin - Part B [Day 1 to Day 14]

    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.

34. CFB in Calcium - Part B [Day 1 to Day 14]

    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.

35. CFB in Chloride - Part B [Day 1 to Day 14]

    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.

36. CFB in Creatinine - Part B [Day 1 to Day 14]

    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.

37. CFB in Lipase - Part B [Day 1 to Day 14]

    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.

38. CFB in Magnesium - Part B [Day 1 to Day 14]

    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.

39. CFB in Phosphate - Part B [Day 1 to Day 14]

    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.

40. CFB in Potassium - Part B [Day 1 to Day 14]

    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.

41. CFB in Protein - Part B [Day 1 to Day 14]

    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.

42. CFB in Sodium - Part B [Day 1 to Day 14]

    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.

43. CFB in Urate - Part B [Day 1 to Day 14]

    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.

44. CFB in Urea Nitrogen - Part B [Day 1 to Day 14]

    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.

45. CFB in Specific Gravity - Part B [Day 1 to Day 14]

    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.

46. CFB in pH - Part B [Day 1 to Day 14]

    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.

47. CFB in Temperature - Part B [Day 1 to Day 14]

    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.

48. CFB in Heart Rate - Part B [Day 1 to Day 14]

    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.

49. CFB in Respiratory Rate - Part B [Day 1 to Day 14]

    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.

50. CFB in Supine Systolic Blood Pressure - Part B [Day 1 to Day 14]

    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.

51. CFB in Standing Systolic Blood Pressure - Part B [Day 1 to Day 14]

    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.

52. CFB in Supine Diastolic Blood Pressure - Part B [Day 1 to Day 14]

    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.

53. CFB in Standing Diastolic Blood Pressure - Part B [Day 1 to Day 14]

    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.

54. CFB in Pulse Oximetry - Part B [Day 1 to Day 14]

    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.

55. CFB in ECG Mean Heart Rate - Part B [Day 1 to Day 14]

    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.

56. CFB in Aggregate PR Interval - Part B [Day 1 to Day 14]

    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.

57. CFB in Aggregate RR Interval - Part B [Day 1 to Day 14]

    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.

58. CFB in Aggregate QT Interval - Part B [Day 1 to Day 14]

    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.

59. CFB in Aggregate QRS Duration - Part B [Day 1 to Day 14]

    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.

60. CFB in Aggregate QTcF Interval - Part B [Day 1 to Day 14]

    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.

61. Percentage of Participants With a Response of 'Yes' to Any C-SSRS Suicidal Ideation or Suicidal Behavior Item - Part B [Day 1 to Day 14]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant has a diagnosis of idiopathic Parkinson's Disease (Hoehn and Yahr Stage 2 or Stage 3) with a duration of less than 7 years prior to screening [Part A]

• Participant has a diagnosis of idiopathic Parkinson's Disease (Hoehn and Yahr Stage 1-4, assessed during the "on" period) [Part B]

• Participant is on a stable dose (at least 1 month prior to baseline visit) of an antiparkinsonian agent and is willing to remain on this dose for the duration of the study

Exclusion Criteria:

• Participant has early (Hoehn and Yahr Stage 1) or advanced (Hoehn and Yahr Stage 4 or Stage 5) Parkinson's Disease [Part A]

• Participant has advanced (Hoehn and Yahr Stage 5) Parkinson's Disease [Part B]

• Participant with presence of drug-induced parkinsonism, metabolic identified neurogenetic disorders, encephalitis, or other atypical Parkinsonian syndromes

• Participant with medical history of electroconvulsive therapy or stereotaxic brain surgery for Parkinson's Disease

• Participant with medical history of suicide attempt within 2 years of screening or current suicidal ideation

• Participant with medical history of impulse control disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sage Investigational Site	Panorama City	California	United States	91402
2	Sage Investigational Site	Jacksonville	Florida	United States	32216
3	Sage Investigational Site	Miami	Florida	United States	33135
4	Sage Investigational Site	Miami	Florida	United States	33143
5	Sage Investigational Site	Orlando	Florida	United States	32806
6	Sage Investigational Site	Winter Park	Florida	United States	32789
7	Sage Investigational Site	Atlanta	Georgia	United States	30331
8	Sage Investigational Site	Farmington Hills	Michigan	United States	48334
9	Sage Investigational Site	Berlin	New Jersey	United States	08009
10	Sage Investigational Site	Houston	Texas	United States	77058
11	Sage Investigational Site	Orem	Utah	United States	84058

Sponsors and Collaborators

• Sage Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 8, 2017
• Statistical Analysis Plan: Version 2 - Aug 2, 2017
• Statistical Analysis Plan: Version 1 - Feb 6, 2017

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT03000569
• Other Study ID Numbers: 217-PRK-201
• First Posted: Dec 22, 2016
• Last Update Posted: Jan 27, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sage Therapeutics: Parkinson's
• Additional relevant MeSH terms: Parkinson Disease; Levodopa; Antiparkinson Agents

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	15	14
COMPLETED	14	14
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217	Part B: Antiparkinsonian Agent(s) + SAGE-217	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	15	14	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.9 (6.59)	65.1 (7.76)	64.5 (7.17)
Sex: Female, Male (Count of Participants)
Female	7 46.7%	5 35.7%	12 41.4%
Male	8 53.3%	9 64.3%	17 58.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 13.3%	7 50%	9 31%
Not Hispanic or Latino	13 86.7%	7 50%	20 69%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 6.7%	1 7.1%	2 6.9%
White	14 93.3%	12 85.7%	26 89.7%
More than one race	0 0%	1 7.1%	1 3.4%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) - Part A
Description	An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. 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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3	Part A: SAGE-217 Day 4 to Day 7	Part A: Follow-up
Arm/Group Description	Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	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.	Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
Measure Participants	15	14	15
Number [percentage of participants]	26.7 178%	100 714.3%	13.3 45.9%

2. Primary Outcome

Title	Percentage of Participants With TEAEs, Graded by Severity - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3	Part A: SAGE-217 Day 4 to Day 7	Part A: Follow-up
Arm/Group Description	Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.	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.	Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.
Measure Participants	15	14	15
Mild	20.0 133.3%	0 0%	6.7 23.1%
Moderate	6.7 44.7%	85.7 612.1%	6.7 23.1%
Severe	0 0%	14.3 102.1%	0 0%

3. Primary Outcome

Title	Change From Baseline (CFB) in Basophils - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	0.06 (0.051)
CFB at Day 4 (SAGE-217)	-0.02 (0.043)
CFB at Day 6 (SAGE-217)	-0.01 (0.036)
CFB at Day 8 (Follow-up)	0.02 (0.038)
CFB at Day 14 (Follow-up)	-0.02 (0.041)

4. Primary Outcome

Title	CFB in Basophils to Leukocytes Ratio [Percentage (%)] - Part A
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	0.8 (0.41)
CFB at Day 4 (SAGE-217)	0.1 (0.66)
CFB at Day 6 (SAGE-217)	0.3 (0.61)
CFB at Day 8 (Follow-up)	0.0 (0.41)
CFB at Day 14 (Follow-up)	0.1 (0.35)

5. Primary Outcome

Title	CFB in Eosinophils - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	0.17 (0.098)
CFB at Day 4 (SAGE-217)	0.07 (0.083)
CFB at Day 6 (SAGE-217)	0.04 (0.051)
CFB at Day 8 (Follow-up)	0.02 (0.073)
CFB at Day 14 (Follow-up)	0.00 (0.053)

6. Primary Outcome

Title	CFB in Eosinophils to Leukocytes Ratio (%) - Part A
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	2.9 (1.58)
CFB at Day 4 (SAGE-217)	0.7 (1.59)
CFB at Day 6 (SAGE-217)	0.3 (0.83)
CFB at Day 8 (Follow-up)	0.0 (0.82)
CFB at Day 14 (Follow-up)	-0.3 (1.11)

7. Primary Outcome

Title	CFB in Erythrocytes - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	4.63 (0.475)
CFB at Day 4 (SAGE-217)	0.01 (0.266)
CFB at Day 6 (SAGE-217)	0.04 (0.224)
CFB at Day 8 (Follow-up)	0.02 (0.265)
CFB at Day 14 (Follow-up)	-0.09 (0.226)

8. Primary Outcome

Title	CFB in Hematocrit - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	0.434 (0.0444)
CFB at Day 4 (SAGE-217)	0.003 (0.0264)
CFB at Day 6 (SAGE-217)	0.004 (0.0247)
CFB at Day 8 (Follow-up)	-0.002 (0.0285)
CFB at Day 14 (Follow-up)	-0.013 (0.0222)

9. Primary Outcome

Title	CFB in Hemoglobin - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	142.0 (13.87)
CFB at Day 4 (SAGE-217)	0.1 (7.55)
CFB at Day 6 (SAGE-217)	1.7 (7.25)
CFB at Day 8 (Follow-up)	1.2 (8.14)
CFB at Day 14 (Follow-up)	-1.9 (5.82)

10. Primary Outcome

Title	CFB in Leukocytes - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	6.04 (1.139)
CFB at Day 4 (SAGE-217)	-0.24 (1.085)
CFB at Day 6 (SAGE-217)	0.15 (0.536)
CFB at Day 8 (Follow-up)	-0.09 (0.874)
CFB at Day 14 (Follow-up)	0.30 (0.941)

11. Primary Outcome

Title	CFB in Lymphocytes - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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..
Measure Participants	15
Baseline	1.70 (0.318)
CFB at Day 4 (SAGE-217)	-0.02 (0.289)
CFB at Day 6 (SAGE-217)	0.07 (0.352)
CFB at Day 8 (Follow-up)	0.02 (0.286)
CFB at Day 14 (Follow-up)	-0.17 (0.183)

12. Primary Outcome

Title	CFB in Lymphocytes to Leukocytes Ratio (%) - Part A
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	28.3 (4.68)
CFB at Day 4 (SAGE-217)	1.0 (4.72)
CFB at Day 6 (SAGE-217)	1.0 (5.55)
CFB at Day 8 (Follow-up)	0.9 (4.87)
CFB at Day 14 (Follow-up)	-3.9 (4.22)

13. Primary Outcome

Title	CFB in Monocytes - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	0.36 (0.112)
CFB at Day 4 (SAGE-217)	0.02 (0.125)
CFB at Day 6 (SAGE-217)	0.06 (0.076)
CFB at Day 8 (Follow-up)	0.02 (0.101)
CFB at Day 14 (Follow-up)	0.05 (0.064)

14. Primary Outcome

Title	CFB in Monocytes to Leukocytes Ratio (%) - Part A
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	6.1 (1.06)
CFB at Day 4 (SAGE-217)	0.2 (1.48)
CFB at Day 6 (SAGE-217)	0.6 (1.45)
CFB at Day 8 (Follow-up)	0.5 (1.33)
CFB at Day 14 (Follow-up)	0.3 (1.22)

15. Primary Outcome

Title	CFB in Neutrophils- Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	3.79 (0.861)
CFB at Day 4 (SAGE-217)	-0.27 (0.848)
CFB at Day 6 (SAGE-217)	-0.03 (0.599)
CFB at Day 8 (Follow-up)	-0.17 (0.680)
CFB at Day 14 (Follow-up)	0.44 (0.861)

16. Primary Outcome

Title	CFB in Neutrophils to Leukocytes Ratio (%) - Part A
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	62.5 (4.26)
CFB at Day 4 (SAGE-217)	-2.4 (4.94)
CFB at Day 6 (SAGE-217)	-2.4 (5.58)
CFB at Day 8 (Follow-up)	-2.2 (4.86)
CFB at Day 14 (Follow-up)	3.6 (4.64)

17. Primary Outcome

Title	CFB in Platelets - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	218.9 (62.00)
CFB at Day 4 (SAGE-217)	6.6 (27.07)
CFB at Day 6 (SAGE-217)	6.8 (33.01)
CFB at Day 8 (Follow-up)	7.8 (21.29)
CFB at Day 14 (Follow-up)	11.5 (36.42)

18. Primary Outcome

Title	CFB in Reticulocytes - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	64.6 (20.36)
CFB at Day 4 (SAGE-217)	-0.3 (17.87)
CFB at Day 6 (SAGE-217)	0.3 (19.21)
CFB at Day 8 (Follow-up)	0.2 (20.18)
CFB at Day 14 (Follow-up)	0.3 (14.10)

19. Primary Outcome

Title	CFB in Reticulocytes to Erythrocytes Ratio (%) - Part A
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	1.41 (0.442)
CFB at Day 4 (SAGE-217)	0.00 (0.349)
CFB at Day 6 (SAGE-217)	-0.03 (0.409)
CFB at Day 8 (Follow-up)	0.00 (0.424)
CFB at Day 14 (Follow-up)	0.03 (0.315)

20. Primary Outcome

Title	CFB in Activated Partial Thromboplastin Time - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	13
Baseline	24.80
CFB at Day 4 (SAGE-217)	0.20
CFB at Day 6 (SAGE-217)	-0.25
CFB at Day 8 (Follow-up)	-0.10
CFB at Day 14 (Follow-up)	-1.10

21. Primary Outcome

Title	CFB in Prothrombin International Normalized Ratio - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	13
Baseline	1.04 (0.065)
CFB at Day 4 (SAGE-217)	0.01 (0.108)
CFB at Day 6 (SAGE-217)	-0.03 (0.065)
CFB at Day 8 (Follow-up)	0.05 (0.243)
CFB at Day 14 (Follow-up)	0.01 (0.155)

22. Primary Outcome

Title	CFB in Prothrombin Time - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	13
Baseline	10.70
CFB at Day 4 (SAGE-217)	0.00
CFB at Day 6 (SAGE-217)	0.00
CFB at Day 8 (Follow-up)	0.10
CFB at Day 14 (Follow-up)	-0.10

23. Primary Outcome

Title	CFB in Alanine Aminotransferase - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	15.8 (8.12)
CFB at Day 4 (SAGE-217)	15.3 (11.61)
CFB at Day 6 (SAGE-217)	13.9 (11.87)
CFB at Day 8 (Follow-up)	7.2 (13.64)
CFB at Day 14 (Follow-up)	2.3 (9.24)

24. Primary Outcome

Title	CFB in Albumin - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	43.2 (1.70)
CFB at Day 4 (SAGE-217)	-1.2 (1.81)
CFB at Day 6 (SAGE-217)	-0.4 (2.59)
CFB at Day 8 (Follow-up)	-0.1 (2.21)
CFB at Day 14 (Follow-up)	-0.3 (2.35)

25. Primary Outcome

Title	CFB in Alkaline Phosphatase - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	80.6 (14.17)
CFB at Day 4 (SAGE-217)	-1.7 (9.34)
CFB at Day 6 (SAGE-217)	-2.4 (4.52)
CFB at Day 8 (Follow-up)	-0.5 (4.78)
CFB at Day 14 (Follow-up)	0.0 (8.06)

26. Primary Outcome

Title	CFB in Aspartate Aminotransferase - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	23.2 (7.24)
CFB at Day 4 (SAGE-217)	-0.4 (6.15)
CFB at Day 6 (SAGE-217)	-2.4 (4.93)
CFB at Day 8 (Follow-up)	-1.0 (5.25)
CFB at Day 14 (Follow-up)	1.8 (5.16)

27. Primary Outcome

Title	CFB in Bicarbonate - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	22.4 (2.50)
CFB at Day 4 (SAGE-217)	-0.9 (2.27)
CFB at Day 6 (SAGE-217)	0.3 (2.23)
CFB at Day 8 (Follow-up)	-0.1 (2.41)
CFB at Day 14 (Follow-up)	0.7 (2.26)

28. Primary Outcome

Title	CFB in Bilirubin - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	6.082 (3.8041)
CFB at Day 4 (SAGE-217)	-0.029 (3.4758)
CFB at Day 6 (SAGE-217)	0.949 (3.8554)
CFB at Day 8 (Follow-up)	1.545 (3.5965)
CFB at Day 14 (Follow-up)	0.543 (3.7159)

29. Primary Outcome

Title	CFB in Calcium - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	2.342 (0.0588)
CFB at Day 4 (SAGE-217)	-0.030 (0.0734)
CFB at Day 6 (SAGE-217)	0.007 (0.0779)
CFB at Day 8 (Follow-up)	-0.014 (0.0711)
CFB at Day 14 (Follow-up)	-0.015 (0.0842)

30. Primary Outcome

Title	CFB in Chloride - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	100.1 (2.33)
CFB at Day 4 (SAGE-217)	1.6 (1.91)
CFB at Day 6 (SAGE-217)	1.1 (2.30)
CFB at Day 8 (Follow-up)	0.5 (2.41)
CFB at Day 14 (Follow-up)	0.3 (1.83)

31. Primary Outcome

Title	CFB in Creatinine - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	73.254 (17.7960)
CFB at Day 4 (SAGE-217)	2.399 (8.6574)
CFB at Day 6 (SAGE-217)	4.104 (9.4424)
CFB at Day 8 (Follow-up)	4.420 (10.9866)
CFB at Day 14 (Follow-up)	0.118 (4.6761)

32. Primary Outcome

Title	CFB in Lipase - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	34.5 (10.16)
CFB at Day 4 (SAGE-217)	16.6 (22.15)
CFB at Day 6 (SAGE-217)	35.1 (77.58)
CFB at Day 8 (Follow-up)	73.3 (222.02)
CFB at Day 14 (Follow-up)	-1.6 (7.67)

33. Primary Outcome

Title	CFB in Magnesium - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	0.861 (0.0686)
CFB at Day 4 (SAGE-217)	-0.012 (0.0409)
CFB at Day 6 (SAGE-217)	0.000 (0.0457)
CFB at Day 8 (Follow-up)	0.015 (0.0617)
CFB at Day 14 (Follow-up)	0.016 (0.0618)

34. Primary Outcome

Title	CFB in Phosphate - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	1.098 (0.1189)
CFB at Day 4 (SAGE-217)	0.035 (0.1413)
CFB at Day 6 (SAGE-217)	0.076 (0.1645)
CFB at Day 8 (Follow-up)	0.083 (0.1513)
CFB at Day 14 (Follow-up)	-0.034 (0.1698)

35. Primary Outcome

Title	CFB in Potassium - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	4.53 (0.326)
CFB at Day 4 (SAGE-217)	-0.14 (0.323)
CFB at Day 6 (SAGE-217)	-0.08 (0.309)
CFB at Day 8 (Follow-up)	-0.15 (0.350)
CFB at Day 14 (Follow-up)	-0.08 (0.446)

36. Primary Outcome

Title	CFB in Protein - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	69.4 (3.07)
CFB at Day 4 (SAGE-217)	-2.3 (4.12)
CFB at Day 6 (SAGE-217)	-1.5 (3.86)
CFB at Day 8 (Follow-up)	-0.4 (3.65)
CFB at Day 14 (Follow-up)	-1.1 (4.33)

37. Primary Outcome

Title	CFB in Sodium - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	140.0 (1.73)
CFB at Day 4 (SAGE-217)	0.8 (2.15)
CFB at Day 6 (SAGE-217)	1.3 (1.86)
CFB at Day 8 (Follow-up)	0.7 (2.20)
CFB at Day 14 (Follow-up)	0.5 (1.85)

38. Primary Outcome

Title	CFB in Urate - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	0.337 (0.1000)
CFB at Day 4 (SAGE-217)	-0.005 (0.0713)
CFB at Day 6 (SAGE-217)	0.010 (0.0804)
CFB at Day 8 (Follow-up)	0.014 (0.0394)
CFB at Day 14 (Follow-up)	-0.014 (0.0649)

39. Primary Outcome

Title	CFB in Urea Nitrogen - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	5.831 (1.3672)
CFB at Day 4 (SAGE-217)	0.587 (1.4925)
CFB at Day 6 (SAGE-217)	0.816 (1.4715)
CFB at Day 8 (Follow-up)	0.663 (1.5521)
CFB at Day 14 (Follow-up)	-0.048 (1.3484)

40. Primary Outcome

Title	CFB in Specific Gravity - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	1.018 (0.0049)
CFB at Day 4 (SAGE-217)	-0.001 (0.0062)
CFB at Day 7 (SAGE-217)	0.000 (0.0039)
CFB at Day 14 (Follow-up)	0.002 (0.0059)

41. Primary Outcome

Title	CFB in pH - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	5.87 (0.915)
CFB at Day 4 (SAGE-217)	0.18 (0.973)
CFB at Day 7 (SAGE-217)	-0.11 (0.881)
CFB at Day 14 (Follow-up)	-0.07 (0.884)

42. Primary Outcome

Title	CFB in Temperature - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	36.61 (0.228)
CFB at Day 1 (L/C): 1 Hour Postdose	-0.04 (0.180)
CFB at Day 1 (L/C): 2 Hours Postdose	-0.01 (0.205)
CFB at Day 1 (L/C): 3 Hours Postdose	-0.05 (0.236)
CFB at Day 1 (L/C): 4 Hours Postdose	-0.08 (0.227)
CFB at Day 1 (L/C): 6 Hours Postdose	-0.06 (0.285)
CFB at Day 1 (L/C): 8 Hours Postdose	0.00 (0.235)
CFB at Day 1 (L/C): 12 Hours Postdose	0.08 (0.412)
CFB at Day 1 (L/C): 14 Hours Postdose	0.00 (0.319)
CFB at Day 1 (L/C): 16 Hours Postdose	-0.01 (0.296)
CFB at Day 2 (L/C): Predose	-0.06 (0.346)
CFB at Day 2 (L/C): 1 Hour Postdose	-0.11 (0.316)
CFB at Day 2 (L/C): 2 Hours Postdose	-0.05 (0.348)
CFB at Day 2 (L/C): 3 Hours Postdose	-0.04 (0.323)
CFB at Day 2 (L/C): 4 Hours Postdose	-0.07 (0.279)
CFB at Day 2 (L/C): 6 Hours Postdose	-0.11 (0.274)
CFB at Day 2 (L/C): 8 Hours Postdose	-0.02 (0.283)
CFB at Day 2 (L/C): 12 Hours Postdose	0.06 (0.380)
CFB at Day 2 (L/C): 14 Hours Postdose	-0.05 (0.380)
CFB at Day 2 (L/C): 16 Hours Postdose	-0.06 (0.365)
CFB at Day 3 (L/C): Predose	0.09 (0.409)
CFB at Day 3 (L/C): 1 Hour Postdose	-0.09 (0.305)
CFB at Day 3 (L/C): 2 Hours Postdose	-0.10 (0.277)
CFB at Day 3 (L/C): 3 Hours Postdose	-0.10 (0.272)
CFB at Day 3 (L/C): 4 Hours Postdose	-0.03 (0.331)
CFB at Day 3 (L/C): 6 Hours Postdose	-0.06 (0.363)
CFB at Day 3 (L/C): 8 Hours Postdose	-0.04 (0.276)
CFB at Day 3 (L/C): 12 Hours Postdose	-0.05 (0.422)
CFB at Day 3 (L/C): 14 Hours Postdose	-0.01 (0.372)
CFB at Day 3 (L/C): 16 Hours Postdose	0.04 (0.176)
CFB at Day 4 (SAGE-217): Predose	0.02 (0.208)
CFB at Day 4 (SAGE-217): 1 Hour Postdose	0.01 (0.175)
CFB at Day 4 (SAGE-217): 2 Hours Postdose	0.08 (0.387)
CFB at Day 4 (SAGE-217): 3 Hours Postdose	-0.07 (0.236)
CFB at Day 4 (SAGE-217): 4 Hours Postdose	-0.11 (0.236)
CFB at Day 4 (SAGE-217): 6 Hours Postdose	0.03 (0.230)
CFB at Day 4 (SAGE-217): 8 Hours Postdose	-0.03 (0.336)
CFB at Day 4 (SAGE-217): 12 Hours Postdose	-0.02 (0.333)
CFB at Day 4 (SAGE-217): 14 Hours Postdose	0.12 (0.185)
CFB at Day 4 (SAGE-217): 16 Hours Postdose	0.07 (0.233)
CFB at Day 5 (SAGE-217): Predose	-0.05 (0.187)
CFB at Day 5 (SAGE-217): 1 Hour Postdose	-0.04 (0.287)
CFB at Day 5 (SAGE-217): 2 Hours Postdose	-0.16 (0.360)
CFB at Day 5 (SAGE-217): 3 Hours Postdose	-0.17 (0.272)
CFB at Day 5 (SAGE-217): 4 Hours Postdose	-0.02 (0.449)
CFB at Day 5 (SAGE-217): 6 Hours Postdose	-0.16 (0.310)
CFB at Day 5 (SAGE-217): 8 Hours Postdose	-0.07 (0.421)
CFB at Day 5 (SAGE-217): 12 Hours Postdose	-0.09 (0.400)
CFB at Day 5 (SAGE-217): 14 Hours Postdose	-0.07 (0.273)
CFB at Day 5 (SAGE-217): 16 Hours Postdose	-0.02 (0.383)
CFB at Day 6 (SAGE-217): Predose	-0.04 (0.359)
CFB at Day 6 (SAGE-217): 1 Hour Postdose	0.02 (0.306)
CFB at Day 6 (SAGE-217): 2 Hours Postdose	-0.08 (0.322)
CFB at Day 6 (SAGE-217): 3 Hours Postdose	-0.13 (0.322)
CFB at Day 6 (SAGE-217): 4 Hours Postdose	-0.12 (0.358)
CFB at Day 6 (SAGE-217): 6 Hours Postdose	-0.09 (0.260)
CFB at Day 6 (SAGE-217): 8 Hours Postdose	-0.08 (0.329)
CFB at Day 6 (SAGE-217): 12 Hours Postdose	-0.10 (0.697)
CFB at Day 6 (SAGE-217): 14 Hours Postdose	-0.04 (0.434)
CFB at Day 6 (SAGE-217): 16 Hours Postdose	0.06 (0.434)
CFB at Day 7 (SAGE-217): Predose	-0.13 (0.302)
CFB at Day 7 (SAGE-217): 1 Hour Postdose	-0.16 (0.282)
CFB at Day 7 (SAGE-217): 2 Hours Postdose	-0.16 (0.407)
CFB at Day 7 (SAGE-217): 3 Hours Postdose	-0.16 (0.310)
CFB at Day 7 (SAGE-217): 4 Hours Postdose	-0.11 (0.332)
CFB at Day 7 (SAGE-217): 6 Hours Postdose	-0.13 (0.252)
CFB at Day 7 (SAGE-217): 8 Hours Postdose	0.02 (0.208)
CFB at Day 7 (SAGE-217): 12 Hours Postdose	0.06 (0.145)
CFB at Day 7 (SAGE-217): 14 Hours Postdose	-0.01 (0.235)
CFB at Day 7 (SAGE-217): 16 Hours Postdose	-0.03 (0.363)
CFB at Day 8 (Follow-up)	0.4 (0.224)
CFB at Day 14 (Follow-up)	0.07 (0.301)

43. Primary Outcome

Title	CFB in Heart Rate - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	66.6 (11.83)
CFB at Day 1 (L/C): 1 Hour Postdose	2.1 (5.87)
CFB at Day 1 (L/C): 2 Hours Postdose	1.3 (6.76)
CFB at Day 1 (L/C): 3 Hours Postdose	-0.5 (5.87)
CFB at Day 1 (L/C): 4 Hours Postdose	-1.3 (6.63)
CFB at Day 1 (L/C): 6 Hours Postdose	0.8 (7.75)
CFB at Day 1 (L/C): 8 Hours Postdose	0.4 (7.55)
CFB at Day 1 (L/C): 12 Hours Postdose	5.5 (6.86)
CFB at Day 1 (L/C): 14 Hours Postdose	0.5 (7.18)
CFB at Day 1 (L/C): 16 Hours Postdose	1.4 (5.03)
CFB at Day 2 (L/C): Predose	-0.2 (6.80)
CFB at Day 2 (L/C): 1 Hour Postdose	2.1 (7.37)
CFB at Day 2 (L/C): 2 Hours Postdose	1.9 (8.10)
CFB at Day 2 (L/C): 3 Hours Postdose	-0.3 (10.71)
CFB at Day 2 (L/C): 4 Hours Postdose	-0.9 (5.23)
CFB at Day 2 (L/C): 6 Hours Postdose	2.1 (7.08)
CFB at Day 2 (L/C): 8 Hours Postdos	3.8 (7.81)
CFB at Day 2 (L/C): 12 Hours Postdose	3.9 (8.38)
CFB at Day 2 (L/C): 14 Hours Postdose	1.6 (7.29)
CFB at Day 2 (L/C): 16 Hours Postdose	1.2 (7.29)
CFB at Day 3 (L/C): Predose	-0.7 (9.29)
CFB at Day 3 (L/C): 1 Hour Postdose	4.7 (6.67)
CFB at Day 3 (L/C): 2 Hours Postdose	2.4 (9.46)
CFB at Day 3 (L/C): 3 Hours Postdose	1.2 (7.20)
CFB at Day 3 (L/C): 4 Hours Postdose	0.6 (6.30)
CFB at Day 3 (L/C): 6 Hours Postdose	1.7 (7.33)
CFB at Day 3 (L/C): 8 Hours Postdose	5.9 (5.43)
CFB at Day 3 (L/C): 12 Hours Postdose	2.6 (9.72)
CFB at Day 3 (L/C): 14 Hours Postdose	3.6 (8.63)
CFB at Day 3 (L/C): 16 Hours Postdose	3.9 (7.08)
CFB at Day 4 (SAGE-217): Predose	1.4 (5.21)
CFB at Day 4 (SAGE-217): 1 Hour Postdose	3.7 (6.43)
CFB at Day 4 (SAGE-217): 2 Hours Postdose	1.6 (8.97)
CFB at Day 4 (SAGE-217): 3 Hours Postdose	3.4 (10.38)
CFB at Day 4 (SAGE-217): 4 Hours Postdose	0.6 (6.27)
CFB at Day 4 (SAGE-217): 6 Hours Postdose	2.7 (8.72)
CFB at Day 4 (SAGE-217): 8 Hours Postdose	2.1 (7.97)
CFB at Day 4 (SAGE-217): 12 Hours Postdose	5.1 (9.70)
CFB at Day 4 (SAGE-217): 14 Hours Postdose	5.2 (6.64)
CFB at Day 4 (SAGE-217): 16 Hours Postdose	4.6 (7.37)
CFB at Day 5 (SAGE-217): Predose	1.5 (8.25)
CFB at Day 5 (SAGE-217): 1 Hour Postdose	3.8 (6.99)
CFB at Day 5 (SAGE-217): 2 Hours Postdose	4.4 (9.06)
CFB at Day 5 (SAGE-217): 3 Hours Postdose	3.4 (8.18)
CFB at Day 5 (SAGE-217): 4 Hours Postdose	1.3 (11.03)
CFB at Day 5 (SAGE-217): 6 Hours Postdose	7.6 (11.24)
CFB at Day 5 (SAGE-217): 8 Hours Postdose	4.2 (9.50)
CFB at Day 5 (SAGE-217): 12 Hours Postdose	8.4 (9.51)
CFB at Day 5 (SAGE-217): 14 Hours Postdose	6.6 (7.98)
CFB at Day 5 (SAGE-217): 16 Hours Postdose	3.7 (9.34)
CFB at Day 6 (SAGE-217): Predose	4.6 (7.58)
CFB at Day 6 (SAGE-217): 1 Hour Postdose	4.3 (6.53)
CFB at Day 6 (SAGE-217): 2 Hours Postdose	2.9 (7.86)
CFB at Day 6 (SAGE-217): 3 Hours Postdose	4.2 (7.51)
CFB at Day 6 (SAGE-217): 4 Hours Postdose	3.2 (10.09)
CFB at Day 6 (SAGE-217): 6 Hours Postdose	5.1 (10.07)
CFB at Day 6 (SAGE-217): 8 Hours Postdose	4.6 (11.00)
CFB at Day 6 (SAGE-217): 12 Hours Postdose	4.8 (10.87)
CFB at Day 6 (SAGE-217): 14 Hours Postdose	5.2 (9.51)
CFB at Day 6 (SAGE-217): 16 Hours Postdose	5.4 (10.87)
CFB at Day 7 (SAGE-217): Predose	8.4 (11.06)
CFB at Day 7 (SAGE-217): 1 Hour Postdose	6.0 (8.29)
CFB at Day 7 (SAGE-217): 2 Hours Postdose	5.3 (6.49)
CFB at Day 7 (SAGE-217): 3 Hours Postdose	3.9 (12.50)
CFB at Day 7 (SAGE-217): 4 Hours Postdose	4.4 (7.77)
CFB at Day 7 (SAGE-217): 6 Hours Postdose	6.0 (8.46)
CFB at Day 7 (SAGE-217): 8 Hours Postdose	4.8 (4.66)
CFB at Day 7 (SAGE-217): 12 Hours Postdose	9.5 (9.82)
CFB at Day 7 (SAGE-217): 14 Hours Postdose	6.7 (9.27)
CFB at Day 7 (SAGE-217): 16 Hours Postdose	5.6 (7.93)
CFB at Day 8 (Follow-up)	1.8 (6.52)
CFB at Day 14 (Follow-up)	4.1 (8.29)

44. Primary Outcome

Title	CFB in Respiratory Rate - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	15.9 (1.92)
CFB at Day 1 (L/C): 1 Hour Postdose	0.1 (1.46)
CFB at Day 1 (L/C): 2 Hours Postdose	0.1 (1.92)
CFB at Day 1 (L/C): 3 Hours Postdose	0.0 (1.69)
CFB at Day 1 (L/C): 4 Hours Postdose	0.2 (1.93)
CFB at Day 1 (L/C): 6 Hours Postdose	0.0 (1.69)
CFB at Day 1 (L/C): 8 Hours Postdose	1.0 (2.08)
CFB at Day 1 (L/C): 12 Hours Postdose	0.6 (1.99)
CFB at Day 1 (L/C): 14 Hours Postdose	0.1 (1.83)
CFB at Day 1 (L/C): 16 Hours Postdose	-0.2 (2.49)
CFB at Day 2 (L/C): Predose	-0.1 (1.59)
CFB at Day 2 (L/C): 1 Hour Postdose	0.1 (1.83)
CFB at Day 2 (L/C): 2 Hours Postdose	0.2 (1.48)
CFB at Day 2 (L/C): 3 Hours Postdose	0.0 (1.57)
CFB at Day 2 (L/C): 4 Hours Postdose	0.5 (1.70)
CFB at Day 2 (L/C): 6 Hours Postdose	0.4 (2.14)
CFB at Day 2 (L/C): 8 Hours Postdose	0.1 (2.32)
CFB at Day 2 (L/C): 12 Hours Postdose	0.3 (2.61)
CFB at Day 2 (L/C): 14 Hours Postdose	0.3 (2.92)
CFB at Day 2 (L/C): 16 Hours Postdose	0.1 (2.62)
CFB at Day 3 (L/C): Predose	-0.4 (1.99)
CFB at Day 3 (L/C): 1 Hour Postdose	0.4 (1.65)
CFB at Day 3 (L/C): 2 Hours Postdose	-0.1 (2.03)
CFB at Day 3 (L/C): 3 Hours Postdose	0.4 (2.13)
CFB at Day 3 (L/C): 4 Hours Postdose	0.1 (2.11)
CFB at Day 3 (L/C): 6 Hours Postdose	0.4 (1.87)
CFB at Day 3 (L/C): 8 Hours Postdose	0.2 (2.26)
CFB at Day 3 (L/C): 12 Hours Postdose	0.4 (1.65)
CFB at Day 3 (L/C): 14 Hours Postdose	0.2 (1.93)
CFB at Day 3 (L/C): 16 Hours Postdose	0.0 (2.74)
CFB at Day 4 (SAGE-217): Predose	0.9 (1.59)
CFB at Day 4 (SAGE-217): 1 Hour Postdose	-0.3 (2.69)
CFB at Day 4 (SAGE-217): 2 Hours Postdose	-0.4 (2.79)
CFB at Day 4 (SAGE-217): 3 Hours Postdose	0.3 (2.39)
CFB at Day 4 (SAGE-217): 4 Hours Postdose	-0.1 (1.66)
CFB at Day 4 (SAGE-217): 6 Hours Postdose	0.1 (1.21)
CFB at Day 4 (SAGE-217): 8 Hours Postdose	0.7 (1.68)
CFB at Day 4 (SAGE-217): 12 Hours Postdose	0.9 (1.86)
CFB at Day 4 (SAGE-217): 14 Hours Postdose	0.5 (1.70)
CFB at Day 4 (SAGE-217): 16 Hours Postdose	-0.3 (2.02)
CFB at Day 5 (SAGE-217): Predose	-0.1 (1.59)
CFB at Day 5 (SAGE-217): 1 Hour Postdose	-0.3 (2.20)
CFB at Day 5 (SAGE-217): 2 Hours Postdose	-0.4 (2.34)
CFB at Day 5 (SAGE-217): 3 Hours Postdose	-0.1 (1.77)
CFB at Day 5 (SAGE-217): 4 Hours Postdose	0.1 (1.86)
CFB at Day 5 (SAGE-217): 6 Hours Postdose	0.4 (2.27)
CFB at Day 5 (SAGE-217): 8 Hours Postdose	1.0 (1.92)
CFB at Day 5 (SAGE-217): 12 Hours Postdose	0.4 (1.95)
CFB at Day 5 (SAGE-217): 14 Hours Postdose	0.5 (1.95)
CFB at Day 5 (SAGE-217): 16 Hours Postdose	0.3 (2.05)
CFB at Day 6 (SAGE-217): Predose	-0.1 (1.38)
CFB at Day 6 (SAGE-217): 1 Hour Postdose	-0.6 (1.65)
CFB at Day 6 (SAGE-217): 2 Hours Postdose	-0.3 (1.38)
CFB at Day 6 (SAGE-217): 3 Hours Postdose	-0.1 (2.18)
CFB at Day 6 (SAGE-217): 4 Hours Postdose	-0.1 (1.79)
CFB at Day 6 (SAGE-217): 6 Hours Postdose	0.4 (2.21)
CFB at Day 6 (SAGE-217): 8 Hours Postdose	1.0 (1.92)
CFB at Day 6 (SAGE-217): 12 Hours Postdose	0.4 (2.82)
CFB at Day 6 (SAGE-217): 14 Hours Postdose	0.5 (2.10)
CFB at Day 6 (SAGE-217): 16 Hours Postdose	0.4 (2.31)
CFB at Day 7 (SAGE-217): Predose	0.0 (1.36)
CFB at Day 7 (SAGE-217): 1 Hour Postdose	0.1 (1.27)
CFB at Day 7 (SAGE-217): 2 Hours Postdose	0.9 (1.51)
CFB at Day 7 (SAGE-217): 3 Hours Postdose	0.1 (1.49)
CFB at Day 7 (SAGE-217): 4 Hours Postdose	0.1 (1.66)
CFB at Day 7 (SAGE-217): 6 Hours Postdose	0.6 (1.65)
CFB at Day 7 (SAGE-217): 8 Hours Postdose	0.4 (1.65)
CFB at Day 7 (SAGE-217): 12 Hours Postdose	1.4 (2.03)
CFB at Day 7 (SAGE-217): 14 Hours Postdose	0.4 (2.31)
CFB at Day 7 (SAGE-217): 16 Hours Postdose	0.7 (2.61)
CFB at Day 8 (Follow-up)	0.1 (1.29)
CFB at Day 14 (Follow-up)	0.9 (1.83)

45. Primary Outcome

Title	CFB in Supine Systolic Blood Pressure - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	124.5 (11.61)
CFB at Day 1 (L/C): 1 Hour Postdose	-6.7 (10.81)
CFB at Day 1 (L/C): 2 Hours Postdose	-7.1 (11.49)
CFB at Day 1 (L/C): 3 Hours Postdose	-1.5 (10.37)
CFB at Day 1 (L/C): 4 Hours Postdose	-4.7 (9.44)
CFB at Day 1 (L/C): 6 Hours Postdose	-4.5 (9.63)
CFB at Day 1 (L/C): 8 Hours Postdose	2.4 (13.32)
CFB at Day 1 (L/C): 12 Hours Postdose	3.4 (13.21)
CFB at Day 1 (L/C): 14 Hours Postdose	-3.0 (12.51)
CFB at Day 1 (L/C): 16 Hours Postdose	-3.9 (11.99)
CFB at Day 2 (L/C): Predose	-0.4 (11.14)
CFB at Day 2 (L/C): 1 Hour Postdose	-7.3 (11.59)
CFB at Day 2 (L/C): 2 Hours Postdose	-4.4 (9.99)
CFB at Day 2 (L/C): 3 Hours Postdose	-0.8 (10.86)
CFB at Day 2 (L/C): 4 Hours Postdose	-1.1 (10.43)
CFB at Day 2 (L/C): 6 Hours Postdose	-1.6 (10.95)
CFB at Day 2 (L/C): 8 Hours Postdose	3.2 (15.35)
CFB at Day 2 (L/C): 12 Hours Postdose	5.9 (8.00)
CFB at Day 2 (L/C): 14 Hours Postdose	3.4 (9.53)
CFB at Day 2 (L/C): 16 Hours Postdose	0.9 (10.40)
CFB at Day 3 (L/C): Predose	1.2 (8.61)
CFB at Day 3 (L/C): 1 Hour Postdose	-2.5 (10.30)
CFB at Day 3 (L/C): 2 Hours Postdose	-7.4 (14.70)
CFB at Day 3 (L/C): 3 Hours Postdose	-3.1 (12.69)
CFB at Day 3 (L/C): 4 Hours Postdose	-3.7 (14.12)
CFB at Day 3 (L/C): 6 Hours Postdose	-3.1 (12.51)
CFB at Day 3 (L/C): 8 Hours Postdose	-1.3 (12.75)
CFB at Day 3 (L/C): 12 Hours Postdose	3.3 (13.30)
CFB at Day 3 (L/C): 14 Hours Postdose	3.6 (16.21)
CFB at Day 3 (L/C): 16 Hours Postdose	-3.3 (10.73)
CFB at Day 4 (SAGE-217): Predose	3.5 (10.17)
CFB at Day 4 (SAGE-217): 1 Hour Postdose	-4.8 (9.75)
CFB at Day 4 (SAGE-217): 2 Hours Postdose	-6.6 (10.80)
CFB at Day 4 (SAGE-217): 3 Hours Postdose	2.3 (15.97)
CFB at Day 4 (SAGE-217): 4 Hours Postdose	-1.6 (8.84)
CFB at Day 4 (SAGE-217): 6 Hours Postdose	-3.9 (10.46)
CFB at Day 4 (SAGE-217): 8 Hours Postdose	2.2 (10.94)
CFB at Day 4 (SAGE-217): 12 Hours Postdose	3.1 (9.60)
CFB at Day 4 (SAGE-217): 14 Hours Postdose	-3.1 (14.15)
CFB at Day 4 (SAGE-217): 16 Hours Postdose	-2.6 (10.83)
CFB at Day 5 (SAGE-217): Predose	0.1 (11.43)
CFB at Day 5 (SAGE-217): 1 Hour Postdose	-8.6 (9.68)
CFB at Day 5 (SAGE-217): 2 Hours Postdose	-8.1 (11.67)
CFB at Day 5 (SAGE-217): 3 Hours Postdose	-5.8 (10.14)
CFB at Day 5 (SAGE-217): 4 Hours Postdose	-0.4 (9.23)
CFB at Day 5 (SAGE-217): 6 Hours Postdose	-2.9 (11.14)
CFB at Day 5 (SAGE-217): 8 Hours Postdose	-3.8 (10.15)
CFB at Day 5 (SAGE-217): 12 Hours Postdose	1.3 (11.68)
CFB at Day 5 (SAGE-217): 14 Hours Postdose	1.7 (15.46)
CFB at Day 5 (SAGE-217): 16 Hours Postdose	0.6 (14.19)
CFB at Day 6 (SAGE-217): Predose	-5.9 (11.67)
CFB at Day 6 (SAGE-217): 1 Hour Postdose	-8.6 (11.95)
CFB at Day 6 (SAGE-217): 2 Hours Postdose	-3.8 (13.03)
CFB at Day 6 (SAGE-217): 3 Hours Postdose	-4.1 (15.47)
CFB at Day 6 (SAGE-217): 4 Hours Postdose	-5.6 (13.00)
CFB at Day 6 (SAGE-217): 6 Hours Postdose	-4.4 (10.23)
CFB at Day 6 (SAGE-217): 8 Hours Postdose	-0.1 (12.46)
CFB at Day 6 (SAGE-217): 12 Hours Postdose	-0.1 (12.41)
CFB at Day 6 (SAGE-217): 14 Hours Postdose	2.5 (10.39)
CFB at Day 6 (SAGE-217): 16 Hours Postdose	1.8 (13.45)
CFB at Day 7 (SAGE-217): Predose	1.9 (19.64)
CFB at Day 7 (SAGE-217): 1 Hour Postdose	-5.9 (12.93)
CFB at Day 7 (SAGE-217): 2 Hours Postdose	-5.4 (18.93)
CFB at Day 7 (SAGE-217): 3 Hours Postdose	-2.8 (13.22)
CFB at Day 7 (SAGE-217): 4 Hours Postdose	-5.1 (17.35)
CFB at Day 7 (SAGE-217): 6 Hours Postdose	-3.9 (14.81)
CFB at Day 7 (SAGE-217): 8 Hours Postdose	-3.1 (10.38)
CFB at Day 7 (SAGE-217): 12 Hours Postdose	2.9 (13.23)
CFB at Day 7 (SAGE-217): 14 Hours Postdose	-0.6 (14.07)
CFB at Day 7 (SAGE-217): 16 Hours Postdose	-0.2 (18.75)
CFB at Day 8 (Follow-up)	1.7 (7.79)
CFB at Day 14 (Follow-up)	2.7 (9.50)

46. Primary Outcome

Title	CFB in Standing Systolic Blood Pressure - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	124.1 (12.38)
CFB at Day 1 (L/C): 1 Hour Postdose	-3.1 (9.98)
CFB at Day 1 (L/C): 2 Hours Postdose	-4.7 (10.00)
CFB at Day 1 (L/C): 3 Hours Postdose	-2.9 (11.45)
CFB at Day 1 (L/C): 4 Hours Postdose	0.0 (11.78)
CFB at Day 1 (L/C): 6 Hours Postdose	2.7 (13.34)
CFB at Day 1 (L/C): 8 Hours Postdose	4.3 (10.22)
CFB at Day 1 (L/C): 12 Hours Postdose	7.6 (17.85)
CFB at Day 1 (L/C): 14 Hours Postdose	2.9 (10.18)
CFB at Day 1 (L/C): 16 Hours Postdose	-2.7 (9.51)
CFB at Day 2 (L/C): Predose	1.0 (11.09)
CFB at Day 2 (L/C): 1 Hour Postdose	-2.9 (10.57)
CFB at Day 2 (L/C): 2 Hours Postdose	-3.4 (11.56)
CFB at Day 2 (L/C): 3 Hours Postdose	-5.1 (9.86)
CFB at Day 2 (L/C): 4 Hours Postdose	0.0 (10.12)
CFB at Day 2 (L/C): 6 Hours Postdose	-3.4 (8.50)
CFB at Day 2 (L/C): 8 Hours Postdose	-0.6 (10.20)
CFB at Day 2 (L/C): 12 Hours Postdose	5.6 (16.97)
CFB at Day 2 (L/C): 14 Hours Postdose	2.0 (11.08)
CFB at Day 2 (L/C): 16 Hours Postdose	-4.4 (10.14)
CFB at Day 3 (L/C): Predose	-1.4 (7.84)
CFB at Day 3 (L/C): 1 Hour Postdose	-4.2 (8.17)
CFB at Day 3 (L/C): 2 Hours Postdose	-4.9 (11.83)
CFB at Day 3 (L/C): 3 Hours Postdose	-4.4 (13.07)
CFB at Day 3 (L/C): 4 Hours Postdose	-6.2 (13.13)
CFB at Day 3 (L/C): 6 Hours Postdose	-3.2 (9.35)
CFB at Day 3 (L/C): 8 Hours Postdose	-3.2 (10.83)
CFB at Day 3 (L/C): 12 Hours Postdose	1.8 (14.56)
CFB at Day 3 (L/C): 14 Hours Postdose	0.0 (15.65)
CFB at Day 3 (L/C): 16 Hours Postdose	2.2 (11.98)
CFB at Day 4 (SAGE-217): Predose	3.3 (13.32)
CFB at Day 4 (SAGE-217): 1 Hour Postdose	-1.5 (14.74)
CFB at Day 4 (SAGE-217): 2 Hours Postdose	-4.6 (10.60)
CFB at Day 4 (SAGE-217): 3 Hours Postdose	-0.5 (11.77)
CFB at Day 4 (SAGE-217): 4 Hours Postdose	-5.7 (10.04)
CFB at Day 4 (SAGE-217): 6 Hours Postdose	-2.3 (8.50)
CFB at Day 4 (SAGE-217): 8 Hours Postdose	0.9 (9.16)
CFB at Day 4 (SAGE-217): 12 Hours Postdose	3.3 (12.72)
CFB at Day 4 (SAGE-217): 14 Hours Postdose	0.0 (10.09)
CFB at Day 4 (SAGE-217): 16 Hours Postdose	-1.3 (10.07)
CFB at Day 5 (SAGE-217): Predose	-0.6 (9.61)
CFB at Day 5 (SAGE-217): 1 Hour Postdose	-9.8 (12.60)
CFB at Day 5 (SAGE-217): 2 Hours Postdose	-8.3 (10.52)
CFB at Day 5 (SAGE-217): 3 Hours Postdose	-3.8 (14.81)
CFB at Day 5 (SAGE-217): 4 Hours Postdose	-2.4 (9.82)
CFB at Day 5 (SAGE-217): 6 Hours Postdose	-2.1 (12.05)
CFB at Day 5 (SAGE-217): 8 Hours Postdose	-3.3 (10.16)
CFB at Day 5 (SAGE-217): 12 Hours Postdose	1.4 (12.51)
CFB at Day 5 (SAGE-217): 14 Hours Postdose	2.3 (17.97)
CFB at Day 5 (SAGE-217): 16 Hours Postdose	0.8 (15.37)
CFB at Day 6 (SAGE-217): Predose	-3.3 (12.00)
CFB at Day 6 (SAGE-217): 1 Hour Postdose	-6.4 (10.89)
CFB at Day 6 (SAGE-217): 2 Hours Postdose	-5.5 (9.34)
CFB at Day 6 (SAGE-217): 3 Hours Postdose	-3.5 (10.36)
CFB at Day 6 (SAGE-217): 4 Hours Postdose	-2.8 (8.55)
CFB at Day 6 (SAGE-217): 6 Hours Postdose	1.6 (9.45)
CFB at Day 6 (SAGE-217): 8 Hours Postdose	-2.7 (12.79)
CFB at Day 6 (SAGE-217): 12 Hours Postdose	-2.9 (12.13)
CFB at Day 6 (SAGE-217): 14 Hours Postdose	2.5 (13.57)
CFB at Day 6 (SAGE-217): 16 Hours Postdose	0.6 (19.21)
CFB at Day 7 (SAGE-217): Predose	-0.2 (12.25)
CFB at Day 7 (SAGE-217): 1 Hour Postdose	-4.0 (13.06)
CFB at Day 7 (SAGE-217): 2 Hours Postdose	-4.7 (13.19)
CFB at Day 7 (SAGE-217): 3 Hours Postdose	-6.0 (9.27)
CFB at Day 7 (SAGE-217): 4 Hours Postdose	-5.9 (13.96)
CFB at Day 7 (SAGE-217): 6 Hours Postdose	-2.4 (13.65)
CFB at Day 7 (SAGE-217): 8 Hours Postdose	2.1 (10.80)
CFB at Day 7 (SAGE-217): 12 Hours Postdose	4.6 (14.54)
CFB at Day 7 (SAGE-217): 14 Hours Postdose	3.7 (13.23)
CFB at Day 7 (SAGE-217): 16 Hours Postdose	0.5 (11.95)
CFB at Day 8 (Follow-up)	7.6 (9.90)
CFB at Day 14 (Follow-up)	3.6 (13.14)

47. Primary Outcome

Title	CFB in Supine Diastolic Blood Pressure - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	77.3 (7.19)
CFB at Day 1 (L/C): 1 Hour Postdose	-5.3 (6.02)
CFB at Day 1 (L/C): 2 Hours Postdose	-4.7 (5.92)
CFB at Day 1 (L/C): 3 Hours Postdose	-3.2 (6.66)
CFB at Day 1 (L/C): 4 Hours Postdose	-3.1 (5.26)
CFB at Day 1 (L/C): 6 Hours Postdose	-3.9 (9.91)
CFB at Day 1 (L/C): 8 Hours Postdose	-0.4 (9.04)
CFB at Day 1 (L/C): 12 Hours Postdose	-0.1 (7.89)
CFB at Day 1 (L/C): 14 Hours Postdose	-3.6 (8.94)
CFB at Day 1 (L/C): 16 Hours Postdose	-5.0 (10.34)
CFB at Day 2 (L/C): Predose	0.7 (7.10)
CFB at Day 2 (L/C): 1 Hour Postdose	-4.8 (9.49)
CFB at Day 2 (L/C): 2 Hours Postdose	-3.4 (9.90)
CFB at Day 2 (L/C): 3 Hours Postdose	-2.2 (11.37)
CFB at Day 2 (L/C): 4 Hours Postdose	-2.5 (7.78)
CFB at Day 2 (L/C): 6 Hours Postdose	-1.4 (10.09)
CFB at Day 2 (L/C): 8 Hours Postdose	-1.4 (10.47)
CFB at Day 2 (L/C): 12 Hours Postdose	0.9 (7.57)
CFB at Day 2 (L/C): 14 Hours Postdose	-1.9 (8.08)
CFB at Day 2 (L/C): 16 Hours Postdose	-3.4 (7.13)
CFB at Day 3 (L/C): Predose	-0.8 (7.29)
CFB at Day 3 (L/C): 1 Hour Postdose	-5.1 (8.51)
CFB at Day 3 (L/C): 2 Hours Postdose	-3.1 (8.11)
CFB at Day 3 (L/C): 3 Hours Postdose	-4.3 (9.77)
CFB at Day 3 (L/C): 4 Hours Postdose	-5.9 (13.63)
CFB at Day 3 (L/C): 6 Hours Postdose	-4.1 (8.77)
CFB at Day 3 (L/C): 8 Hours Postdose	-3.9 (9.90)
CFB at Day 3 (L/C): 12 Hours Postdose	-1.0 (8.32)
CFB at Day 3 (L/C): 14 Hours Postdose	-0.9 (7.80)
CFB at Day 3 (L/C): 16 Hours Postdose	-2.5 (8.69)
CFB at Day 4 (SAGE-217): Predose	1.8 (7.82)
CFB at Day 4 (SAGE-217): 1 Hour Postdose	-1.9 (6.72)
CFB at Day 4 (SAGE-217): 2 Hours Postdose	-3.6 (6.48)
CFB at Day 4 (SAGE-217): 3 Hours Postdose	1.5 (8.19)
CFB at Day 4 (SAGE-217): 4 Hours Postdose	-0.8 (8.01)
CFB at Day 4 (SAGE-217): 6 Hours Postdose	-3.6 (8.75)
CFB at Day 4 (SAGE-217): 8 Hours Postdose	-1.7 (7.08)
CFB at Day 4 (SAGE-217): 12 Hours Postdose	0.0 (6.93)
CFB at Day 4 (SAGE-217): 14 Hours Postdose	-3.6 (8.84)
CFB at Day 4 (SAGE-217): 16 Hours Postdose	-4.0 (7.05)
CFB at Day 5 (SAGE-217): Predose	-2.1 (8.43)
CFB at Day 5 (SAGE-217): 1 Hour Postdose	-5.4 (7.72)
CFB at Day 5 (SAGE-217): 2 Hours Postdose	-2.4 (6.17)
CFB at Day 5 (SAGE-217): 3 Hours Postdose	-3.1 (6.62)
CFB at Day 5 (SAGE-217): 4 Hours Postdose	-3.3 (6.93)
CFB at Day 5 (SAGE-217): 6 Hours Postdose	-2.4 (8.22)
CFB at Day 5 (SAGE-217): 8 Hours Postdose	-3.4 (7.00)
CFB at Day 5 (SAGE-217): 12 Hours Postdose	-4.0 (9.17)
CFB at Day 5 (SAGE-217): 14 Hours Postdose	-4.3 (7.84)
CFB at Day 5 (SAGE-217): 16 Hours Postdose	-2.2 (10.02)
CFB at Day 6 (SAGE-217): Predose	-3.6 (7.59)
CFB at Day 6 (SAGE-217): 1 Hour Postdose	-3.7 (9.72)
CFB at Day 6 (SAGE-217): 2 Hours Postdose	-2.7 (9.31)
CFB at Day 6 (SAGE-217): 3 Hours Postdose	-1.8 (8.99)
CFB at Day 6 (SAGE-217): 4 Hours Postdose	-1.8 (11.37)
CFB at Day 6 (SAGE-217): 6 Hours Postdose	-3.9 (8.09)
CFB at Day 6 (SAGE-217): 8 Hours Postdose	-1.7 (8.06)
CFB at Day 6 (SAGE-217): 12 Hours Postdose	-1.0 (9.17)
CFB at Day 6 (SAGE-217): 14 Hours Postdose	0.8 (7.71)
CFB at Day 6 (SAGE-217): 16 Hours Postdose	-3.6 (10.30)
CFB at Day 7 (SAGE-217): Predose	-1.9 (6.75)
CFB at Day 7 (SAGE-217): 1 Hour Postdose	-5.1 (7.79)
CFB at Day 7 (SAGE-217): 2 Hours Postdose	-3.5 (9.61)
CFB at Day 7 (SAGE-217): 3 Hours Postdose	-2.7 (10.46)
CFB at Day 7 (SAGE-217): 4 Hours Postdose	-4.5 (9.40)
CFB at Day 7 (SAGE-217): 6 Hours Postdose	-4.8 (8.58)
CFB at Day 7 (SAGE-217): 8 Hours Postdose	-2.2 (10.02)
CFB at Day 7 (SAGE-217): 12 Hours Postdose	-1.0 (8.58)
CFB at Day 7 (SAGE-217): 14 Hours Postdose	-3.5 (10.65)
CFB at Day 7 (SAGE-217): 16 Hours Postdose	-4.2 (9.66)
CFB at Day 8 (Follow-up)	-3.8 (8.05)
CFB at Day 14 (Follow-up)	-2.2 (7.22)

48. Primary Outcome

Title	CFB in Standing Diastolic Blood Pressure - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	76.7 (10.57)
CFB at Day 1 (L/C): 1 Hour Postdose	0.4 (8.71)
CFB at Day 1 (L/C): 2 Hours Postdose	-2.9 (7.26)
CFB at Day 1 (L/C): 3 Hours Postdose	0.7 (7.92)
CFB at Day 1 (L/C): 4 Hours Postdose	2.3 (5.57)
CFB at Day 1 (L/C): 6 Hours Postdose	0.9 (10.54)
CFB at Day 1 (L/C): 8 Hours Postdose	3.1 (7.16)
CFB at Day 1 (L/C): 12 Hours Postdose	2.6 (7.04)
CFB at Day 1 (L/C): 14 Hours Postdose	1.3 (7.65)
CFB at Day 1 (L/C): 16 Hours Postdose	1.6 (7.19)
CFB at Day 2 (L/C): Predose	4.0 (8.41)
CFB at Day 2 (L/C): 1 Hour Postdose	1.6 (7.89)
CFB at Day 2 (L/C): 2 Hours Postdose	1.1 (12.25)
CFB at Day 2 (L/C): 3 Hours Postdose	1.1 (8.53)
CFB at Day 2 (L/C): 4 Hours Postdose	3.8 (10.08)
CFB at Day 2 (L/C): 6 Hours Postdose	0.3 (12.55)
CFB at Day 2 (L/C): 8 Hours Postdose	1.6 (10.91)
CFB at Day 2 (L/C): 12 Hours Postdose	4.3 (6.80)
CFB at Day 2 (L/C): 14 Hours Postdose	3.7 (5.99)
CFB at Day 2 (L/C): 16 Hours Postdose	0.1 (5.34)
CFB at Day 3 (L/C): Predose	4.4 (7.82)
CFB at Day 3 (L/C): 1 Hour Postdose	-1.1 (9.44)
CFB at Day 3 (L/C): 2 Hours Postdose	-0.9 (6.98)
CFB at Day 3 (L/C): 3 Hours Postdose	-1.7 (12.74)
CFB at Day 3 (L/C): 4 Hours Postdose	-0.7 (11.23)
CFB at Day 3 (L/C): 6 Hours Postdose	-0.6 (9.94)
CFB at Day 3 (L/C): 8 Hours Postdose	-1.0 (11.90)
CFB at Day 3 (L/C): 12 Hours Postdose	0.6 (7.43)
CFB at Day 3 (L/C): 14 Hours Postdose	1.8 (9.57)
CFB at Day 3 (L/C): 16 Hours Postdose	3.8 (10.98)
CFB at Day 4 (SAGE-217): Predose	4.6 (9.11)
CFB at Day 4 (SAGE-217): 1 Hour Postdose	1.8 (8.09)
CFB at Day 4 (SAGE-217): 2 Hours Postdose	2.4 (6.86)
CFB at Day 4 (SAGE-217): 3 Hours Postdose	5.6 (7.50)
CFB at Day 4 (SAGE-217): 4 Hours Postdose	3.7 (7.90)
CFB at Day 4 (SAGE-217): 6 Hours Postdose	0.3 (8.17)
CFB at Day 4 (SAGE-217): 8 Hours Postdose	1.9 (7.88)
CFB at Day 4 (SAGE-217): 12 Hours Postdose	4.8 (11.13)
CFB at Day 4 (SAGE-217): 14 Hours Postdose	1.9 (10.41)
CFB at Day 4 (SAGE-217): 16 Hours Postdose	2.8 (9.24)
CFB at Day 5 (SAGE-217): Predose	2.6 (5.84)
CFB at Day 5 (SAGE-217): 1 Hour Postdose	-2.5 (5.99)
CFB at Day 5 (SAGE-217): 2 Hours Postdose	-0.8 (6.66)
CFB at Day 5 (SAGE-217): 3 Hours Postdose	3.8 (6.44)
CFB at Day 5 (SAGE-217): 4 Hours Postdose	2.7 (6.34)
CFB at Day 5 (SAGE-217): 6 Hours Postdose	1.6 (6.21)
CFB at Day 5 (SAGE-217): 8 Hours Postdose	0.1 (8.02)
CFB at Day 5 (SAGE-217): 12 Hours Postdose	0.2 (9.27)
CFB at Day 5 (SAGE-217): 14 Hours Postdose	0.4 (9.18)
CFB at Day 5 (SAGE-217): 16 Hours Postdose	0.8 (9.71)
CFB at Day 6 (SAGE-217): Predose	-0.4 (8.56)
CFB at Day 6 (SAGE-217): 1 Hour Postdose	0.9 (7.45)
CFB at Day 6 (SAGE-217): 2 Hours Postdose	0.8 (7.10)
CFB at Day 6 (SAGE-217): 3 Hours Postdose	2.0 (10.43)
CFB at Day 6 (SAGE-217): 4 Hours Postdose	1.2 (8.84)
CFB at Day 6 (SAGE-217): 6 Hours Postdose	1.6 (7.06)
CFB at Day 6 (SAGE-217): 8 Hours Postdose	2.3 (9.25)
CFB at Day 6 (SAGE-217): 12 Hours Postdose	0.7 (9.63)
CFB at Day 6 (SAGE-217): 14 Hours Postdose	3.1 (8.10)
CFB at Day 6 (SAGE-217): 16 Hours Postdose	2.8 (11.44)
CFB at Day 7 (SAGE-217): Predose	2.4 (8.24)
CFB at Day 7 (SAGE-217): 1 Hour Postdose	0.3 (8.72)
CFB at Day 7 (SAGE-217): 2 Hours Postdose	-2.0 (7.54)
CFB at Day 7 (SAGE-217): 3 Hours Postdose	-0.2 (6.47)
CFB at Day 7 (SAGE-217): 4 Hours Postdose	-1.4 (9.98)
CFB at Day 7 (SAGE-217): 6 Hours Postdose	-0.9 (7.85)
CFB at Day 7 (SAGE-217): 8 Hours Postdose	2.7 (6.91)
CFB at Day 7 (SAGE-217): 12 Hours Postdose	2.0 (10.58)
CFB at Day 7 (SAGE-217): 14 Hours Postdose	2.9 (11.34)
CFB at Day 7 (SAGE-217): 16 Hours Postdose	1.1 (9.31)
CFB at Day 8 (Follow-up)	2.1 (7.47)
CFB at Day 14 (Follow-up)	1.5 (8.06)

49. Primary Outcome

Title	CFB in Pulse Oximetry- Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	96.9 (2.22)
CFB at Day 1 (L/C): 1 Hour Postdose	-0.3 (1.03)
CFB at Day 1 (L/C): 2 Hours Postdose	0.2 (1.42)
CFB at Day 1 (L/C): 3 Hours Postdose	0.2 (1.90)
CFB at Day 1 (L/C): 4 Hours Postdose	0.1 (2.02)
CFB at Day 1 (L/C): 6 Hours Postdose	-0.2 (1.42)
CFB at Day 1 (L/C): 8 Hours Postdose	-0.1 (1.23)
CFB at Day 1 (L/C): 12 Hours Postdose	-0.1 (1.46)
CFB at Day 1 (L/C): 14 Hours Postdose	-0.4 (1.08)
CFB at Day 1 (L/C): 16 Hours Postdose	-0.7 (2.64)
CFB at Day 2 (L/C): Predose	-0.6 (1.50)
CFB at Day 2 (L/C): 1 Hour Postdose	-0.4 (2.02)
CFB at Day 2 (L/C): 2 Hours Postdose	-0.4 (1.83)
CFB at Day 2 (L/C): 3 Hours Postdose	-0.2 (0.97)
CFB at Day 2 (L/C): 4 Hours Postdose	-0.7 (2.02)
CFB at Day 2 (L/C): 6 Hours Postdose	-0.5 (2.38)
CFB at Day 2 (L/C): 8 Hours Postdose	0.4 (1.91)
CFB at Day 2 (L/C): 12 Hours Postdose	-0.1 (1.17)
CFB at Day 2 (L/C): 14 Hours Postdose	-0.6 (1.28)
CFB at Day 2 (L/C): 16 Hours Postdose	-0.2 (1.31)
CFB at Day 3 (L/C): Predose	-0.5 (1.79)
CFB at Day 3 (L/C): 1 Hour Postdose	-1.1 (1.86)
CFB at Day 3 (L/C): 2 Hours Postdose	-0.4 (1.70)
CFB at Day 3 (L/C): 3 Hours Postdose	-0.3 (1.44)
CFB at Day 3 (L/C): 4 Hours Postdose	-0.1 (1.33)
CFB at Day 3 (L/C): 6 Hours Postdose	0.3 (1.59)
CFB at Day 3 (L/C): 8 Hours Postdose	-0.1 (1.90)
CFB at Day 3 (L/C): 12 Hours Postdose	0.0 (1.36)
CFB at Day 3 (L/C): 14 Hours Postdose	0.4 (1.28)
CFB at Day 3 (L/C): 16 Hours Postdose	-0.2 (1.63)
CFB at Day 4 (SAGE-217): Predose	0.0 (0.96)
CFB at Day 4 (SAGE-217): 1 Hour Postdose	-1.6 (3.69)
CFB at Day 4 (SAGE-217): 2 Hours Postdose	-0.7 (2.73)
CFB at Day 4 (SAGE-217): 3 Hours Postdose	-0.1 (1.82)
CFB at Day 4 (SAGE-217): 4 Hours Postdose	-0.4 (1.09)
CFB at Day 4 (SAGE-217): 6 Hours Postdose	-0.4 (1.87)
CFB at Day 4 (SAGE-217): 8 Hours Postdose	-0.4 (1.28)
CFB at Day 4 (SAGE-217): 12 Hours Postdose	-0.1 (1.29)
CFB at Day 4 (SAGE-217): 14 Hours Postdose	-0.2 (1.42)
CFB at Day 4 (SAGE-217): 16 Hours Postdose	-0.3 (1.68)
CFB at Day 5 (SAGE-217): Predose	0.2 (1.76)
CFB at Day 5 (SAGE-217): 1 Hour Postdose	-1.3 (2.61)
CFB at Day 5 (SAGE-217): 2 Hours Postdose	-1.2 (2.72)
CFB at Day 5 (SAGE-217): 3 Hours Postdose	0.1 (1.82)
CFB at Day 5 (SAGE-217): 4 Hours Postdose	0.0 (1.36)
CFB at Day 5 (SAGE-217): 6 Hours Postdose	-0.2 (1.72)
CFB at Day 5 (SAGE-217): 8 Hours Postdose	-0.1 (1.73)
CFB at Day 5 (SAGE-217): 12 Hours Postdose	-0.4 (2.56)
CFB at Day 5 (SAGE-217): 14 Hours Postdose	-0.6 (2.34)
CFB at Day 5 (SAGE-217): 16 Hours Postdose	-1.1 (2.87)
CFB at Day 6 (SAGE-217): Predose	-0.5 (1.61)
CFB at Day 6 (SAGE-217): 1 Hour Postdose	-1.1 (1.59)
CFB at Day 6 (SAGE-217): 2 Hours Postdose	0.1 (2.37)
CFB at Day 6 (SAGE-217): 3 Hours Postdose	-0.9 (2.03)
CFB at Day 6 (SAGE-217): 4 Hours Postdose	-0.4 (2.34)
CFB at Day 6 (SAGE-217): 6 Hours Postdose	0.1 (2.09)
CFB at Day 6 (SAGE-217): 8 Hours Postdose	0.0 (1.52)
CFB at Day 6 (SAGE-217): 12 Hours Postdose	0.0 (1.84)
CFB at Day 6 (SAGE-217): 14 Hours Postdose	-0.4 (1.79)
CFB at Day 6 (SAGE-217): 16 Hours Postdose	0.1 (2.27)
CFB at Day 7 (SAGE-217): Predose	0.3 (1.38)
CFB at Day 7 (SAGE-217): 1 Hour Postdose	-1.4 (2.28)
CFB at Day 7 (SAGE-217): 2 Hours Postdose	-0.4 (2.92)
CFB at Day 7 (SAGE-217): 3 Hours Postdose	-0.5 (2.50)
CFB at Day 7 (SAGE-217): 4 Hours Postdose	0.4 (1.45)
CFB at Day 7 (SAGE-217): 6 Hours Postdose	0.3 (0.99)
CFB at Day 7 (SAGE-217): 8 Hours Postdose	0.3 (1.33)
CFB at Day 7 (SAGE-217): 12 Hours Postdose	0.3 (1.94)
CFB at Day 7 (SAGE-217): 14 Hours Postdose	0.3 (1.59)
CFB at Day 7 (SAGE-217): 16 Hours Postdose	0.2 (1.76)
CFB at Day 8 (Follow-up)	0.3 (1.27)
CFB at Day 14 (Follow-up)	0.5 (1.77)

50. Primary Outcome

Title	CFB in Electrocardiogram (ECG) Mean Heart Rate - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	64.7 (11.85)
CFB at Day 3 (L/C): Predose	-0.5 (6.77)
CFB at Day 4 (SAGE-217): Predose	1.3 (6.78)
CFB at Day 4 (SAGE-217): 1 Hour Postdose	6.9 (7.65)
CFB at Day 4 (SAGE-217): 12 Hours Postdose	7.1 (8.89)
CFB at Day 5 (SAGE-217): Predose	2.5 (5.53)
CFB at Day 5 (SAGE-217): 1 Hour Postdose	8.2 (5.31)
CFB at Day 5 (SAGE-217): 12 Hours Postdose	9.0 (10.71)
CFB at Day 6 (SAGE-217): Predose	3.7 (4.50)
CFB at Day 6 (SAGE-217): 1 Hour Postdose	5.9 (7.11)
Day 6 (SAGE-217): 12 Hours Postdose	8.5 (5.37)
CFB at Day 7 (SAGE-217): Predose	5.9 (8.76)
CFB at Day 7 (SAGE-217): 1 Hour Postdose	6.2 (6.03)
CFB at Day 7 (SAGE-217): 12 Hours Postdose	10.7 (6.78)
CFB at Day 8 (Follow-up)	0.9 (4.17)
CFB at Day 14 (Follow-up)	4.7 (9.32)

51. Primary Outcome

Title	CFB in Aggregate PR Interval - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	158.0
CFB at Day 3 (L/C): Predose	2.0
CFB at Day 4 (SAGE-217): Predose	-2.0
CFB at Day 4 (SAGE-217): 1 Hour Postdose	-2.0
CFB at Day 4 (SAGE-217): 12 Hours Postdose	-8.0
CFB at Day 5 (SAGE-217): Predose	-1.0
CFB at Day 5 (SAGE-217): 1 Hour Postdose	-6.0
CFB at Day 5 (SAGE-217): 12 Hours Postdose	-1.0
CFB at Day 6 (SAGE-217): Predose	-3.0
CFB at Day 6 (SAGE-217): 1 Hour Postdose	-5.0
Day 6 (SAGE-217): 12 Hours Postdose	-1.5
CFB at Day 7 (SAGE-217): Predose	-1.0
CFB at Day 7 (SAGE-217): 1 Hour Postdose	-2.5
CFB at Day 7 (SAGE-217): 12 Hours Postdose	-2.0
CFB at Day 8 (Follow-up)	-2.5
CFB at Day 14 (Follow-up)	-8.0

52. Primary Outcome

Title	CFB in Aggregate RR Interval - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	950.0
CFB at Day 3 (L/C): Predose	-32.5
CFB at Day 4 (SAGE-217): Predose	-43.5
CFB at Day 4 (SAGE-217): 1 Hour Postdose	-99.0
CFB at Day 4 (SAGE-217): 12 Hours Postdose	-98.5
CFB at Day 5 (SAGE-217): Predose	-56.0
CFB at Day 5 (SAGE-217): 1 Hour Postdose	-102.0
CFB at Day 5 (SAGE-217): 12 Hours Postdose	-133.0
CFB at Day 6 (SAGE-217): Predose	-65.0
CFB at Day 6 (SAGE-217): 1 Hour Postdose	-63.0
Day 6 (SAGE-217): 12 Hours Postdose	-113.5
CFB at Day 7 (SAGE-217): Predose	-76.5
CFB at Day 7 (SAGE-217): 1 Hour Postdose	-104.5
CFB at Day 7 (SAGE-217): 12 Hours Postdose	-120.0
CFB at Day 8 (Follow-up)	-10.0
CFB at Day 14 (Follow-up)	-86.0

53. Primary Outcome

Title	CFB in Aggregate QT Interval - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	406.0
CFB at Day 3 (L/C): Predose	-4.0
CFB at Day 4 (SAGE-217): Predose	-4.5
CFB at Day 4 (SAGE-217): 1 Hour Postdose	-9.0
CFB at Day 4 (SAGE-217): 12 Hours Postdose	-15.5
CFB at Day 5 (SAGE-217): Predose	-8.5
CFB at Day 5 (SAGE-217): 1 Hour Postdose	-12.0
CFB at Day 5 (SAGE-217): 12 Hours Postdose	-22.0
CFB at Day 6 (SAGE-217): Predose	-4.5
CFB at Day 6 (SAGE-217): 1 Hour Postdose	-9.0
Day 6 (SAGE-217): 12 Hours Postdose	-13.0
CFB at Day 7 (SAGE-217): Predose	-12.5
CFB at Day 7 (SAGE-217): 1 Hour Postdose	-13.0
CFB at Day 7 (SAGE-217): 12 Hours Postdose	-23.0
CFB at Day 8 (Follow-up)	0.0
CFB at Day 14 (Follow-up)	-16.0

54. Primary Outcome

Title	CFB in Aggregate QRS Duration - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	88.0
CFB at Day 3 (L/C): Predose	-1.0
CFB at Day 4 (SAGE-217): Predose	0.0
CFB at Day 4 (SAGE-217): 1 Hour Postdose	2.0
CFB at Day 4 (SAGE-217): 12 Hours Postdose	0.0
CFB at Day 5 (SAGE-217): Predose	-2.0
CFB at Day 5 (SAGE-217): 1 Hour Postdose	0.0
CFB at Day 5 (SAGE-217): 12 Hours Postdose	-1.0
CFB at Day 6 (SAGE-217): Predose	-2.0
CFB at Day 6 (SAGE-217): 1 Hour Postdose	-0.5
Day 6 (SAGE-217): 12 Hours Postdose	0.0
CFB at Day 7 (SAGE-217): Predose	-2.0
CFB at Day 7 (SAGE-217): 1 Hour Postdose	0.0
CFB at Day 7 (SAGE-217): 12 Hours Postdose	-1.5
CFB at Day 8 (Follow-up)	-1.0
CFB at Day 14 (Follow-up)	3.0

55. Primary Outcome

Title	CFB in Aggregate QTcF Interval - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	419.0
CFB at Day 3 (L/C): Predose	-1.0
CFB at Day 4 (SAGE-217): Predose	2.0
CFB at Day 4 (SAGE-217): 1 Hour Postdose	-0.5
CFB at Day 4 (SAGE-217): 12 Hours Postdose	6.5
CFB at Day 5 (SAGE-217): Predose	-3.0
CFB at Day 5 (SAGE-217): 1 Hour Postdose	2.0
CFB at Day 5 (SAGE-217): 12 Hours Postdose	-7.0
CFB at Day 6 (SAGE-217): Predose	4.5
CFB at Day 6 (SAGE-217): 1 Hour Postdose	0.5
Day 6 (SAGE-217): 12 hours postdose	-2.5
CFB at Day 7 (SAGE-217): Predose	2.0
CFB at Day 7 (SAGE-217): 1 Hour Postdose	0.0
CFB at Day 7 (SAGE-217): 12 Hours Postdose	-2.5
CFB at Day 8 (Follow-up)	-0.5
CFB at Day 14 (Follow-up)	-7.0

56. Primary Outcome

Title	CFB in Stanford Sleepiness Scale (SSS) Score - Part A
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Baseline	1.2 (0.56)
CFB at Day 1 (L/C): 1 Hour Postdose	-0.1 (0.26)
CFB at Day 1 (L/C): 2 Hours Postdose	-0.1 (0.26)
CFB at Day 1 (L/C): 3 Hours Postdose	-0.1 (0.52)
CFB at Day 1 (L/C): 4 Hours Postdose	0.0 (0.65)
CFB at Day 1 (L/C): 6 Hours Postdose	0.0 (0.76)
CFB at Day 1 (L/C): 8 Hours Postdose	0.4 (1.39)
CFB at Day 1 (L/C): 12 Hours Postdose	0.2 (0.58)
CFB at Day 1 (L/C): 14 Hours Postdose	0.6 (0.90)
CFB at Day 1 (L/C): 16 Hours Postdose	1.0 (0.85)
CFB at Day 2 (L/C): Predose	0.4 (0.74)
CFB at Day 2 (L/C): 1 Hour Postdose	0.3 (0.73)
CFB at Day 2 (L/C): 2 Hours Postdose	0.2 (0.58)
CFB at Day 2 (L/C): 3 Hours Postdose	0.5 (1.22)
CFB at Day 2 (L/C): 4 Hours Postdose	0.3 (0.91)
CFB at Day 2 (L/C): 6 Hours Postdose	0.5 (1.20)
CFB at Day 2 (L/C): 8 Hours Postdose	0.4 (0.96)
CFB at Day 2 (L/C): 12 Hours Postdose	0.3 (0.47)
CFB at Day 2 (L/C): 14 Hours Postdose	0.6 (0.94)
CFB at Day 2 (L/C): 16 Hours Postdose	0.7 (0.75)
CFB at Day 3 (L/C): Predose	0.3 (0.91)
CFB at Day 3 (L/C): 1 Hour Postdose	0.0 (0.68)
CFB at Day 3 (L/C): 2 Hours Postdose	0.3 (0.91)
CFB at Day 3 (L/C): 3 Hours Postdose	0.3 (1.07)
CFB at Day 3 (L/C): 4 Hours Postdose	0.4 (1.15)
CFB at Day 3 (L/C): 6 Hours Postdose	0.2 (0.90)
CFB at Day 3 (L/C): 8 Hours Postdose	0.3 (0.85)
CFB at Day 3 (L/C): 12 Hours Postdose	0.4 (1.01)
CFB at Day 3 (L/C): 14 Hours Postdose	1.0 (1.18)
CFB at Day 3 (L/C): 16 Hours Postdose	0.7 (0.79)
CFB at Day 4 (SAGE-217): Predose	0.3 (0.61)
CFB at Day 4 (SAGE-217): 1 Hour Postdose	3.2 (2.28)
CFB at Day 4 (SAGE-217): 2 Hours Postdose	2.6 (2.03)
CFB at Day 4 (SAGE-217): 3 Hours Postdose	2.0 (1.57)
CFB at Day 4 (SAGE-217): 4 Hours Postdose	1.2 (1.63)
CFB at Day 4 (SAGE-217): 6 Hours Postdose	0.4 (1.01)
CFB at Day 4 (SAGE-217): 8 Hours Postdose	0.2 (0.93)
CFB at Day 4 (SAGE-217): 12 Hours Postdose	0.2 (0.43)
CFB at Day 4 (SAGE-217): 14 Hours Postdose	0.2 (0.43)
CFB at Day 4 (SAGE-217): 16 Hours Postdose	1.0 (0.82)
CFB at Day 5 (SAGE-217): Predose	0.3 (0.47)
CFB at Day 5 (SAGE-217): 1 Hour Postdose	3.8 (1.79)
CFB at Day 5 (SAGE-217): 2 Hours Postdose	1.8 (1.68)
CFB at Day 5 (SAGE-217): 3 Hours Postdose	1.1 (1.38)
CFB at Day 5 (SAGE-217): 4 Hours Postdose	0.8 (1.42)
CFB at Day 5 (SAGE-217): 6 Hours Postdose	0.6 (0.96)
CFB at Day 5 (SAGE-217): 8 Hours Postdose	0.1 (0.47)
CFB at Day 5 (SAGE-217): 12 Hours Postdose	0.2 (0.43)
CFB at Day 5 (SAGE-217): 14 Hours Postdose	0.4 (0.94)
CFB at Day 5 (SAGE-217): 16 Hours Postdose	0.8 (1.07)
CFB at Day 6 (SAGE-217): Predose	0.1 (0.73)
CFB at Day 6 (SAGE-217): 1 Hour Postdose	2.6 (1.74)
CFB at Day 6 (SAGE-217): 2 Hours Postdose	1.8 (1.85)
CFB at Day 6 (SAGE-217): 3 Hours Postdose	1.6 (2.21)
CFB at Day 6 (SAGE-217): 4 Hours Postdose	1.1 (1.94)
CFB at Day 6 (SAGE-217): 6 Hours Postdose	0.8 (1.30)
CFB at Day 6 (SAGE-217): 8 Hours Postdose	0.3 (0.91)
CFB at Day 6 (SAGE-217): 12 Hours Postdose	0.2 (0.89)
CFB at Day 6 (SAGE-217): 14 Hours Postdose	0.4 (0.74)
CFB at Day 6 (SAGE-217): 16 Hours Postdose	0.9 (1.19)
CFB at Day 7 (SAGE-217): Predose	0.2 (0.58)
CFB at Day 7 (SAGE-217): 1 hour postdose	2.0 (1.66)
CFB at Day 7 (SAGE-217): 2 Hours Postdose	1.3 (1.38)
CFB at Day 7 (SAGE-217): 3 Hours Postdose	0.7 (1.14)
CFB at Day 7 (SAGE-217): 4 Hours Postdose	0.7 (1.33)
CFB at Day 7 (SAGE-217): 6 Hours Postdose	0.1 (0.86)
CFB at Day 7 (SAGE-217): 8 Hours Postdose	0.2 (0.97)
CFB at Day 7 (SAGE-217): 12 Hours Postdose	0.1 (0.83)
CFB at Day 7 (SAGE-217): 14 Hours Postdose	0.4 (1.01)
CFB at Day 7 (SAGE-217): 16 Hours Postdose	0.4 (1.01)
CFB at Day 8 (Follow-up)	-0.1 (0.62)
CFB at Day 14 (Follow-up)	-0.1 (0.59)

57. Primary Outcome

Title	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
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Suicidal Ideation: Pre-treatment	0 0%
Suicidal Ideation: Post-treatment	0 0%
Suicidal Behavior: Pre-treatment	0 0%
Suicidal Behavior: Post-treatment	0 0%

58. Primary Outcome

Title	CFB in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Score - Part B
Description	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.
Time Frame	Baseline, Days 1 to 6 (12 and 23 hours postdose), Day 7 (12 hours postdose), Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	19.1 (3.75)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-5.4 (4.52)
CFB at Dose 1 (SAGE-217): 23 Hours Postdose	-5.9 (5.15)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-6.5 (5.45)
CFB at Dose 2 (SAGE-217): 23 Hours Postdose	-6.6 (4.60)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-6.0 (4.51)
CFB at Dose 3 (SAGE-217): 23 Hours Postdose	-5.9 (5.39)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-8.0 (5.53)
CFB at Dose 4 (SAGE-217): 23 Hours Postdose	-7.4 (5.02)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-7.4 (7.81)
CFB at Dose 5 (SAGE-217): 23 Hours Postdose	-8.0 (5.71)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-5.2 (6.93)
CFB at Dose 6 (SAGE-217): 23 Hours Postdose	-8.4 (5.02)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-7.7 (4.63)
CFB at Day 14 (Follow-up)	-3.7 (4.34)

59. Secondary Outcome

Title	MDS-UPDRS Part III Total Score - Part A
Description	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.
Time Frame	Days 1 to 7 (2, 4, 8, and 12 hours postdose), Day 8 and Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Antiparkinsonian Agent(s) Followed by SAGE-217
Arm/Group Description	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.
Measure Participants	15
Day 1 (L/C): 2 Hours Postdose	25.4 (9.34)
Day 1 (L/C): 4 Hours Postdose	30.0 (10.53)
Day 1 (L/C): 8 Hours Postdose	34.3 (10.83)
Day 1 (L/C): 12 Hours Postdose	35.1 (9.71)
Day 2 (L/C): 2 Hours Postdose	27.1 (9.15)
Day 2 (L/C): 4 Hours Postdose	31.1 (9.65)
Day 2 (L/C): 8 Hours Postdose	35.1 (11.37)
Day 2 (L/C): 12 Hours Postdose	36.1 (11.07)
Day 3 (L/C): 2 Hours Postdose	26.5 (10.95)
Day 3 (L/C): 4 Hours Postdose	29.0 (10.95)
Day 3 (L/C): 8 Hours Postdose	35.2 (10.76)
Day 3 (L/C): 12 Hours Postdose	36.2 (11.29)
Day 4 (SAGE-217): 2 Hours Postdose	35.7 (14.57)
Day 4 (SAGE-217): 4 Hours Postdose	30.9 (12.84)
Day 4 (SAGE-217):8 Hours Postdose	33.4 (11.65)
Day 4 (SAGE-217): 12 Hours Postdose	33.3 (13.19)
Day 5 (SAGE-217): 2 Hours Postdose	33.8 (12.76)
Day 5 (SAGE-217): 4 Hours Postdose	32.4 (12.69)
Day 5 (SAGE-217): 8 Hours Postdose	30.9 (12.02)
Day 5 (SAGE-217): 12 Hours Postdose	33.0 (12.15)
Day 6 (SAGE-217): 2 Hours Postdose	31.5 (11.97)
Day 6 (SAGE-217): 4 Hours Postdose	31.8 (9.66)
Day 6 (SAGE-217): 8 Hours Postdose	32.7 (12.81)
Day 6 (SAGE-217): 12 Hours Postdose	34.5 (11.19)
Day 7 (SAGE-217): 2 Hours Postdose	36.4 (12.55)
Day 7 (SAGE-217): 4 Hours Postdose	35.8 (11.92)
Day 7 (SAGE-217): 8 Hours Postdose	36.0 (11.73)
Day 7 (SAGE-217): 12 Hours Postdose	35.6 (11.03)
Day 8 (Follow-up)	35.4 (10.54)
Day 14 (Follow-up)	30.2 (13.00)

60. Secondary Outcome

Title	CFB in the MDS-UPDRS Part III Total Score - Part B
Description	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.
Time Frame	Baseline, Days 1 to 6 (12 and 23 hours postdose), Day 7 (12 hours postdose), Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	52.4 (12.00)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-8.4 (8.74)
CFB at Dose 1 (SAGE-217): 23 Hours Postdose	-10.8 (9.90)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-11.6 (12.83)
CFB at Dose 2 (SAGE-217): 23 Hours Postdose	-13.5 (7.87)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-12.4 (10.51)
CFB at Dose 3 (SAGE-217): 23 Hours Postdose	-10.9 (9.39)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-14.3 (12.25)
CFB at Dose 4 (SAGE-217): 23 Hours Postdose	-14.8 (10.30)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-14.5 (15.52)
CFB at Dose 5 (SAGE-217): 23 Hours Postdose	-18.1 (10.10)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-14.8 (11.81)
CFB at Dose 6 (SAGE-217): 23 Hours Postdose	-19.5 (9.30)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-18.6 (9.51)
CFB at Day 14 (Follow-up)	-14.5 (10.54)

61. Secondary Outcome

Title	CFB in the MDS-UPDRS Part I Total Score - Part B
Description	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.
Time Frame	Baseline, Day 7 (12 hours postdose), Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	9.9 (6.33)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-4.7 (6.54)
CFB at Day 14 (Follow-up)	-3.9 (6.05)

62. Secondary Outcome

Title	CFB in the MDS-UPDRS Part II Total Score - Part B
Description	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.
Time Frame	Baseline, Days 1 to 6 (12 and 23 hours postdose), Day 7 (12 hours postdose), Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	15.1 (8.26)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-1.9 (3.46)
CFB at Dose 1 (SAGE-217): 23 Hours Postdose	-1.7 (3.73)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-2.1 (5.17)
CFB at Dose 2 (SAGE-217): 23 Hours Postdose	-2.2 (4.92)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-2.0 (5.48)
CFB at Dose 3 (SAGE-217): 23 Hours Postdose	-3.1 (4.20)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-3.4 (6.33)
CFB at Dose 4 (SAGE-217): 23 Hours Postdose	-2.4 (5.43)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-4.6 (5.71)
CFB at Dose 5 (SAGE-217): 23 Hours Postdose	-2.9 (4.90)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-2.9 (5.05)
CFB at Dose 6 (SAGE-217): 23 Hours Postdose	-3.9 (5.40)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-3.9 (4.34)
CFB at Day 14 (Follow-up)	-3.9 (5.02)

63. Secondary Outcome

Title	CFB in the MDS-UPDRS Part I-IV Total Score - Part B
Description	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.
Time Frame	Baseline, Day 7 (12 hours postdose), Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	84.6 (24.01)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-30.0 (17.71)
CFB at Day 14 (Follow-up)	-24.1 (20.75)

64. Secondary Outcome

Title	Percentage of Participants With TEAEs - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217	Part B: Follow-up
Arm/Group Description	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.	Participants received antiparkinsonian agent(s) at normally prescribed dosing schedule for Days 8 to 14.
Measure Participants	14	14
Number [percentage of participants]	57.1 380.7%	0 0%

65. Secondary Outcome

Title	Percentage of Participants With TEAEs, Graded by Severity - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217	Part B: Follow-up
Arm/Group Description	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.	Participants received antiparkinsonian agent(s) at normally prescribed dosing schedule for Days 8 to 14.
Measure Participants	14	14
Mild	42.9 286%	0 0%
Moderate	14.3 95.3%	0 0%
Severe	0 0%	0 0%

66. Secondary Outcome

Title	CFB in Basophils - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	0.06 (0.074)
CFB at Dose 4 (SAGE-217): Predose	0.02 (0.089)
CFB at Dose 6 (SAGE-217): Predose	0.02 (0.058)
CFB at Day 8 (Follow-up)	-0.03 (0.061)
CFB at Day 14 (Follow-up)	0.00 (0.055)

67. Secondary Outcome

Title	CFB in Basophils to Leukocytes Ratio (%) - Part B
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	1.0 (0.39)
CFB at Dose 4 (SAGE-217): Predose	0.2 (0.97)
CFB at Dose 6 (SAGE-217): Predose	0.1 (1.00)
CFB at Day 8 (Follow-up)	-0.1 (0.47)
CFB at Day 14 (Follow-up)	0.1 (0.73)

68. Secondary Outcome

Title	CFB in Eosinophils - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	0.12 (0.058)
CFB at Dose 4 (SAGE-217): Predose	0.05 (0.065)
CFB at Dose 6 (SAGE-217): Predose	0.03 (0.083)
CFB at Day 8 (Follow-up)	0.03 (0.114)
CFB at Day 14 (Follow-up)	-0.02 (0.058)

69. Secondary Outcome

Title	CFB in Eosinophils to Leukocytes Ratio (%) - Part B
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	2.0 (1.04)
CFB at Dose 4 (SAGE-217): Predose	0.7 (1.20)
CFB at Dose 6 (SAGE-217): Predose	0.1 (0.95)
CFB at Day 8 (Follow-up)	0.4 (2.06)
CFB at Day 14 (Follow-up)	-0.4 (0.93)

70. Secondary Outcome

Title	CFB in Erythrocytes - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	4.65 (0.335)
CFB at Dose 4 (SAGE-217): Predose	0.16 (0.798)
CFB at Dose 6 (SAGE-217): Predose	-0.11 (0.186)
CFB at Day 8 (Follow-up)	-0.02 (0.208)
CFB at Day 14 (Follow-up)	-0.06 (0.101)

71. Secondary Outcome

Title	CFB in Hematocrit - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	0.436 (0.0357)
CFB at Dose 4 (SAGE-217): Predose	0.023 (0.0775)
CFB at Dose 6 (SAGE-217): Predose	-0.011 (0.0182)
CFB at Day 8 (Follow-up)	0.006 (0.0268)
CFB at Day 14 (Follow-up)	-0.002 (0.0119)

72. Secondary Outcome

Title	CFB in Hemoglobin - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	140.1 (14.22)
CFB at Dose 4 (SAGE-217): Predose	4.9 (20.90)
CFB at Dose 6 (SAGE-217): Predose	-1.4 (5.32)
CFB at Day 8 (Follow-up)	1.8 (6.03)
CFB at Day 14 (Follow-up)	-0.7 (4.48)

73. Secondary Outcome

Title	CFB in Leukocytes - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	6.47 (1.322)
CFB at Dose 4 (SAGE-217): Predose	0.85 (2.677)
CFB at Dose 6 (SAGE-217): Predose	0.31 (1.370)
CFB at Day 8 (Follow-up)	-0.21 (0.935)
CFB at Day 14 (Follow-up)	0.29 (1.287)

74. Secondary Outcome

Title	CFB in Lymphocytes - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	1.68 (0.549)
CFB at Dose 4 (SAGE-217): Predose	0.44 (0.857)
CFB at Dose 6 (SAGE-217): Predose	0.26 (0.386)
CFB at Day 8 (Follow-up)	0.18 (0.283)
CFB at Day 14 (Follow-up)	0.11 (0.373)

75. Secondary Outcome

Title	CFB in Lymphocytes to Leukocytes Ratio (%) - Part B
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	26.0 (6.31)
CFB at Dose 4 (SAGE-217): Predose	2.5 (6.15)
CFB at Dose 6 (SAGE-217): Predose	2.6 (5.34)
CFB at Day 8 (Follow-up)	3.4 (5.57)
CFB at Day 14 (Follow-up)	0.6 (5.73)

76. Secondary Outcome

Title	CFB in Monocytes - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	0.40 (0.096)
CFB at Dose 4 (SAGE-217): Predose	0.09 (0.194)
CFB at Dose 6 (SAGE-217): Predose	0.03 (0.083)
CFB at Day 8 (Follow-up)	0.03 (0.133)
CFB at Day 14 (Follow-up)	0.01 (0.110)

77. Secondary Outcome

Title	CFB in Monocytes to Leukocytes Ratio (%) - Part B
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	6.4 (1.55)
CFB at Dose 4 (SAGE-217): Predose	0.3 (1.68)
CFB at Dose 6 (SAGE-217): Predose	0.1 (1.49)
CFB at Day 8 (Follow-up)	0.4 (1.74)
CFB at Day 14 (Follow-up)	-0.1 (1.07)

78. Secondary Outcome

Title	CFB in Neutrophils - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	4.23 (0.957)
CFB at Dose 4 (SAGE-217): Predose	0.23 (1.842)
CFB at Dose 6 (SAGE-217): Predose	0.00 (1.136)
CFB at Day 8 (Follow-up)	-0.43 (0.902)
CFB at Day 14 (Follow-up)	0.16 (1.153)

79. Secondary Outcome

Title	CFB in Neutrophils to Leukocytes Ratio (%) - Part B
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	65.3 (5.28)
CFB at Dose 4 (SAGE-217): Predose	-4.2 (7.50)
CFB at Dose 6 (SAGE-217): Predose	-3.0 (6.64)
CFB at Day 8 (Follow-up)	-4.4 (6.69)
CFB at Day 14 (Follow-up)	-0.4 (6.69)

80. Secondary Outcome

Title	CFB in Platelets - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	189.2 (37.72)
CFB at Dose 4 (SAGE-217): Predose	24.1 (67.75)
CFB at Dose 6 (SAGE-217): Predose	5.9 (13.64)
CFB at Day 8 (Follow-up)	0.8 (20.01)
CFB at Day 14 (Follow-up)	5.3 (19.58)

81. Secondary Outcome

Title	CFB in Reticulocytes - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	59.3 (19.27)
CFB at Dose 4 (SAGE-217): Predose	1.1 (11.35)
CFB at Dose 6 (SAGE-217): Predose	5.1 (19.61)
CFB at Day 8 (Follow-up)	2.4 (15.55)
CFB at Day 14 (Follow-up)	5.1 (20.99)

82. Secondary Outcome

Title	CFB in Reticulocytes to Erythrocytes Ratio (%) - Part B
Description	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 (%).
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	1.28 (0.417)
CFB at Dose 4 (SAGE-217): Predose	0.04 (0.250)
CFB at Dose 6 (SAGE-217): Predose	0.13 (0.410)
CFB at Day 8 (Follow-up)	0.05 (0.334)
CFB at Day 14 (Follow-up)	0.13 (0.486)

83. Secondary Outcome

Title	CFB in Activated Partial Thromboplastin Time - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	25.05
CFB at Dose 4 (SAGE-217): Predose	-0.40
CFB at Dose 6 (SAGE-217): Predose	-0.05
CFB at Day 8 (Follow-up)	-0.30
CFB at Day 14 (Follow-up)	-0.20

84. Secondary Outcome

Title	CFB in Prothrombin International Normalized Ratio - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	0.98 (0.043)
CFB at Dose 4 (SAGE-217): Predose	-0.03 (0.045)
CFB at Dose 6 (SAGE-217): Predose	-0.01 (0.051)
CFB at Day 8 (Follow-up)	0.00 (0.041)
CFB at Day 14 (Follow-up)	0.01 (0.036)

85. Secondary Outcome

Title	CFB in Prothrombin Time - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	10.60
CFB at Dose 4 (SAGE-217): Predose	-0.20
CFB at Dose 6 (SAGE-217): Predose	-0.05
CFB at Day 8 (Follow-up)	-0.10
CFB at Day 14 (Follow-up)	0.10

86. Secondary Outcome

Title	CFB in Alanine Aminotransferase - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	10.0 (6.66)
CFB at Dose 4 (SAGE-217): Predose	0.3 (3.17)
CFB at Dose 6 (SAGE-217): Predose	2.6 (5.42)
CFB at Day 8 (Follow-up)	1.9 (3.79)
CFB at Day 14 (Follow-up)	-0.2 (3.70)

87. Secondary Outcome

Title	CFB in Albumin - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	44.2 (2.75)
CFB at Dose 4 (SAGE-217): Predose	-0.2 (1.40)
CFB at Dose 6 (SAGE-217): Predose	-0.6 (1.65)
CFB at Day 8 (Follow-up)	0.16 (1.45)
CFB at Day 14 (Follow-up)	-0.1 (1.86)

88. Secondary Outcome

Title	CFB in Alkaline Phosphatase - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	84.0 (22.05)
CFB at Dose 4 (SAGE-217): Predose	1.4 (7.55)
CFB at Dose 6 (SAGE-217): Predose	2.1 (3.23)
CFB at Day 8 (Follow-up)	2.2 (8.85)
CFB at Day 14 (Follow-up)	-1.1 (8.69)

89. Secondary Outcome

Title	CFB in Aspartate Aminotransferase - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	17.7 (10.59)
CFB at Dose 4 (SAGE-217): Predose	-2.8 (10.63)
CFB at Dose 6 (SAGE-217): Predose	-1.4 (10.93)
CFB at Day 8 (Follow-up)	-0.4 (11.51)
CFB at Day 14 (Follow-up)	-2.4 (10.12)

90. Secondary Outcome

Title	CFB in Bicarbonate - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	24.6 (1.74)
CFB at Dose 4 (SAGE-217): Predose	-1.2 (1.90)
CFB at Dose 6 (SAGE-217): Predose	-0.9 (2.06)
CFB at Day 8 (Follow-up)	-1.1 (2.23)
CFB at Day 14 (Follow-up)	-0.3 (1.77)

91. Secondary Outcome

Title	CFB in Bilirubin - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	8.306 (2.4050)
CFB at Dose 4 (SAGE-217): Predose	-2.993 (2.4320)
CFB at Dose 6 (SAGE-217): Predose	-2.795 (2.0751)
CFB at Day 8 (Follow-up)	-0.122 (2.4611)
CFB at Day 14 (Follow-up)	0.366 (3.0129)

92. Secondary Outcome

Title	CFB in Calcium - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	2.340 (0.0796)
CFB at Dose 4 (SAGE-217): Predose	0.006 (0.0859)
CFB at Dose 6 (SAGE-217): Predose	0.002 (0.0599)
CFB at Day 8 (Follow-up)	0.023 (0.0638)
CFB at Day 14 (Follow-up)	-0.027 (0.0709)

93. Secondary Outcome

Title	CFB in Chloride - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	102.1 (2.03)
CFB at Dose 4 (SAGE-217): Predose	0.1 (1.38)
CFB at Dose 6 (SAGE-217): Predose	0.2 (1.53)
CFB at Day 8 (Follow-up)	-0.5 (2.10)
CFB at Day 14 (Follow-up)	-0.2 (2.36)

94. Secondary Outcome

Title	CFB in Creatinine - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	80.381 (23.1753)
CFB at Dose 4 (SAGE-217): Predose	11.345 (17.8035)
CFB at Dose 6 (SAGE-217): Predose	2.084 (12.3449)
CFB at Day 8 (Follow-up)	-2.968 (8.0917)
CFB at Day 14 (Follow-up)	-0.253 (10.0339)

95. Secondary Outcome

Title	CFB in Lipase - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	37.2 (16.74)
CFB at Dose 4 (SAGE-217): Predose	15.4 (9.64)
CFB at Dose 6 (SAGE-217): Predose	19.4 (16.88)
CFB at Day 8 (Follow-up)	4.3 (6.08)
CFB at Day 14 (Follow-up)	1.6 (9.30)

96. Secondary Outcome

Title	CFB in Magnesium - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	0.873 (0.0489)
CFB at Dose 4 (SAGE-217): Predose	-0.014 (0.0536)
CFB at Dose 6 (SAGE-217): Predose	-0.009 (0.0401)
CFB at Day 8 (Follow-up)	0.018 (0.0448)
CFB at Day 14 (Follow-up)	-0.012 (0.0591)

97. Secondary Outcome

Title	CFB in Phosphate - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	1.091 (0.1489)
CFB at Dose 4 (SAGE-217): Predose	0.161 (0.1496)
CFB at Dose 6 (SAGE-217): Predose	0.180 (0.1386)
CFB at Day 8 (Follow-up)	0.042 (0.1775)
CFB at Day 14 (Follow-up)	0.009 (0.1939)

98. Secondary Outcome

Title	CFB in Potassium - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	4.57 (0.292)
CFB at Dose 4 (SAGE-217): Predose	0.03 (0.319)
CFB at Dose 6 (SAGE-217): Predose	-0.11 (0.264)
CFB at Day 8 (Follow-up)	-0.11 (0.295)
CFB at Day 14 (Follow-up)	-0.01 (0.268)

99. Secondary Outcome

Title	CFB in Protein - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	69.6 (5.40)
CFB at Dose 4 (SAGE-217): Predose	-0.8 (1.75)
CFB at Dose 6 (SAGE-217): Predose	-0.9 (3.00)
CFB at Day 8 (Follow-up)	0.9 (2.68)
CFB at Day 14 (Follow-up)	-0.1 (3.00)

100. Secondary Outcome

Title	CFB in Sodium - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	141.8 (1.97)
CFB at Dose 4 (SAGE-217): Predose	0.1 (1.78)
CFB at Dose 6 (SAGE-217): Predose	0.1 (1.46)
CFB at Day 8 (Follow-up)	0.4 (2.21)
CFB at Day 14 (Follow-up)	-0.1 (3.00)

101. Secondary Outcome

Title	CFB in Urate - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	0.291 (0.0748)
CFB at Dose 4 (SAGE-217): Predose	-0.001 (0.0252)
CFB at Dose 6 (SAGE-217): Predose	0.001 (0.0360)
CFB at Day 8 (Follow-up)	0.006 (0.0254)
CFB at Day 14 (Follow-up)	0.007 (0.0319)

102. Secondary Outcome

Title	CFB in Urea Nitrogen - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	5.993 (1.7667)
CFB at Dose 4 (SAGE-217): Predose	2.142 (1.9554)
CFB at Dose 6 (SAGE-217): Predose	1.275 (1.7917)
CFB at Day 8 (Follow-up)	0.663 (1.9345)
CFB at Day 14 (Follow-up)	0.153 (1.2580)

103. Secondary Outcome

Title	CFB in Specific Gravity - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	1.018 (0.0061)
CFB at Dose 4 (SAGE-217): Predose	0.003 (0.0038)
CFB at Dose 6 (SAGE-217): Predose	0.001 (0.0053)
CFB at Day 8 (Follow-up)	-0.004 (0.0077)
CFB at Day 14 (Follow-up)	0.000 (0.0063)

104. Secondary Outcome

Title	CFB in pH - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	6.11 (0.924)
CFB at Dose 4 (SAGE-217): Predose	-0.18 (1.103)
CFB at Dose 6 (SAGE-217): Predose	-0.32 (1.085)
CFB at Day 8 (Follow-up)	0.39 (0.984)
CFB at Day 14 (Follow-up)	-0.12 (0.820)

105. Secondary Outcome

Title	CFB in Temperature - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	36.56 (0.306)
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-0.10 (0.199)
CFB at Dose 1 (SAGE-217): 2 Hours Postdose	0.01 (0.316)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-0.19 (0.316)
CFB at Dose 2 (SAGE-217): Predose	-0.23 (0.370)
CFB at Dose 2 (SAGE-217): 1 Hour Postdose	-0.15 (0.375)
CFB at Dose 2 (SAGE-217): 2 Hours Postdose	-0.03 (0.310)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-0.09 (0.380)
CFB at Dose 3 (SAGE-217): Predose	-0.06 (0.485)
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.11 (0.327)
CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-0.15 (0.282)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-0.06 (0.386)
CFB at Dose 4 (SAGE-217): Predose	-0.10 (0.451)
CFB at Dose 4 (SAGE-217): 1 Hour Postdose	0.01 (0.408)
CFB at Dose 4 (SAGE-217): 2 Hours Postdose	-0.09 (0.358)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-0.12 (0.336)
CFB at Dose 5 (SAGE-217): Predose	-0.08 (0.418)
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-0.08 (0.423)
CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-0.09 (0.562)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-0.09 (0.512)
CFB at Dose 6 (SAGE-217): Predose	0.01 (0.240)
CFB at Dose 6 (SAGE-217): 1 Hour Postdose	0.05 (0.266)
CFB at Dose 6 (SAGE-217): 2 Hours Postdose	-0.05 (0.289)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-0.07 (0.363)
CFB at Dose 7 (SAGE-217): Predose	-0.07 (0.477)
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-0.10 (0.348)
CFB at Dose 7 (SAGE-217): 2 Hours Postdose	-0.08 (0.352)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-0.10 (0.415)
CFB at Day 14 (Follow-up)	-0.01 (0.291)

106. Secondary Outcome

Title	CFB in Heart Rate - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	72.9 (9.25)
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	0.1 (7.82)
CFB at Dose 1 (SAGE-217): 2 Hours Postdose	0.1 (7.78)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-3.6 (15.35)
CFB at Dose 2 (SAGE-217): Predose	-1.6 (7.14)
CFB at Dose 2 (SAGE-217): 1 Hour Postdose	0.4 (12.44)
CFB at Dose 2 (SAGE-217): 2 Hours Postdose	2.5 (11.94)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-3.0 (11.08)
CFB at Dose 3 (SAGE-217): Predose	0.3 (9.02)
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.1 (7.67)
CFB at Dose 3 (SAGE-217): 2 Hours Postdose	3.1 (7.95)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-0.1 (10.36)
CFB at Dose 4 (SAGE-217): Predose	2.5 (8.16)
CFB at Dose 4 (SAGE-217): 1 Hour Postdose	1.4 (9.41)
CFB at Dose 4 (SAGE-217): 2 Hours Postdose	1.4 (8.31)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-1.6 (9.65)
CFB at Dose 5 (SAGE-217): Predose	2.5 (8.97)
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	1.9 (10.61)
CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-0.4 (9.08)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-4.1 (9.12)
CFB at Dose 6 (SAGE-217): Predose	2.1 (8.61)
CFB at Dose 6 (SAGE-217): 1 Hour Postdose	1.6 (7.08)
CFB at Dose 6 (SAGE-217): 2 Hours Postdose	1.2 (6.13)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	2.4 (11.29)
CFB at Dose 7 (SAGE-217): Predose	-1.7 (8.42)
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-1.7 (8.76)
CFB at Dose 7 (SAGE-217): 2 Hours Postdose	0.9 (8.93)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-1.3 (6.83)
CFB at Day 14 (Follow-up)	-5.0 (8.34)

107. Secondary Outcome

Title	CFB in Respiratory Rate - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	15.6 (1.91)
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	0.6 (1.99)
CFB at Dose 1 (SAGE-217): 2 Hours Postdose	0.6 (1.98)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.8 (1.31)
CFB at Dose 2 (SAGE-217): Predose	-0.9 (2.07)
CFB at Dose 2 (SAGE-217): 1 Hour Postdose	-0.9 (2.09)
CFB at Dose 2 (SAGE-217): 2 Hours Postdose	0.4 (1.50)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	0.8 (1.58)
CFB at Dose 3 (SAGE-217): Predose	0.5 (1.79)
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.4 (1.74)
CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-0.6 (2.03)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	0.6 (1.50)
CFB at Dose 4 (SAGE-217): Predose	-0.2 (2.36)
CFB at Dose 4 (SAGE-217): 1 Hour Postdose	-0.4 (1.55)
CFB at Dose 4 (SAGE-217): 2 Hours Postdose	-0.3 (1.86)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	1.4 (1.87)
CFB at Dose 5 (SAGE-217): Predose	0.4 (1.45)
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	1.4 (1.98)
CFB at Dose 5 (SAGE-217): 2 Hours Postdose	0.6 (2.38)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	0.4 (1.79)
CFB at Dose 6 (SAGE-217): Predose	0.4 (1.74)
CFB at Dose 6 (SAGE-217): 1 Hour Postdose	-0.1 (1.64)
CFB at Dose 6 (SAGE-217): 2 Hours Postdose	0.5 (1.99)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	0.4 (1.78)
CFB at Dose 7 (SAGE-217): Predose	-1.1 (2.02)
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	1.6 (1.39)
CFB at Dose 7 (SAGE-217): 2 Hours Postdose	-0.7 (2.40)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	0.6 (1.65)
CFB at Day 14 (Follow-up)	0.3 (1.90)

108. Secondary Outcome

Title	CFB in Supine Systolic Blood Pressure - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	131.7 (16.50)
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-1.7 (9.15)
CFB at Dose 1 (SAGE-217): 2 Hours Postdose	-1.4 (7.60)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.3 (13.81)
CFB at Dose 2 (SAGE-217): Predose	-3.3 (18.20)
CFB at Dose 2 (SAGE-217): 1 Hour Postdose	2.9 (14.61)
CFB at Dose 2 (SAGE-217): 2 Hours Postdose	0.1 (16.11)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	6.1 (18.57)
CFB at Dose 3 (SAGE-217): Predose	-1.2 (12.35)
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.1 (10.64)
CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-1.6 (13.21)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-1.1 (22.03)
CFB at Dose 4 (SAGE-217): Predose	-1.4 (16.26)
CFB at Dose 4 (SAGE-217): 1 Hour Postdose	-1.1 (14.22)
CFB at Dose 4 (SAGE-217): 2 Hours Postdose	-4.3 (14.21)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	1.2 (18.07)
CFB at Dose 5 (SAGE-217): Predose	-5.7 (14.67)
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-4.0 (15.54)
CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-3.6 (18.79)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	2.3 (11.82)
CFB at Dose 6 (SAGE-217): Predose	-10.9 (17.18)
CFB at Dose 6 (SAGE-217): 1 Hour Postdose	-6.5 (18.68)
CFB at Dose 6 (SAGE-217): 2 Hours Postdose	-2.8 (18.48)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-4.1 (15.90)
CFB at Dose 7 (SAGE-217): Predose	-1.7 (12.63)
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	2.4 (12.33)
CFB at Dose 7 (SAGE-217): 2 Hours Postdose	2.5 (11.94)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-1.2 (13.98)
CFB at Day 14 (Follow-up)	3.4 (15.55)

109. Secondary Outcome

Title	CFB in Standing Systolic Blood Pressure - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	127.8 (14.89)
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-2.9 (10.51)
CFB at Dose 1 (SAGE-217): 2 Hours Postdose	-2.4 (8.41)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.6 (7.68)
CFB at Dose 2 (SAGE-217): Predose	-3.4 (15.96)
CFB at Dose 2 (SAGE-217): 1 Hour Postdose	-1.5 (14.03)
CFB at Dose 2 (SAGE-217): 2 Hours Postdose	1.7 (15.49)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-0.8 (13.50)
CFB at Dose 3 (SAGE-217): Predose	-4.2 (11.77)
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.8 (11.56)
CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-4.4 (11.21)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	0.0 (17.29)
CFB at Dose 4 (SAGE-217): Predose	-4.5 (12.68)
CFB at Dose 4 (SAGE-217): 1 Hour Postdose	-4.1 (18.50)
CFB at Dose 4 (SAGE-217): 2 Hours Postdose	-5.5 (11.25)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-3.8 (13.38)
CFB at Dose 5 (SAGE-217): Predose	-7.5 (8.26)
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-3.9 (12.07)
CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-5.6 (14.59)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-2.3 (10.01)
CFB at Dose 6 (SAGE-217): Predose	-9.4 (8.80)
CFB at Dose 6 (SAGE-217): 1 Hour Postdose	-6.6 (11.05)
CFB at Dose 6 (SAGE-217): 2 Hours Postdose	-4.7 (10.25)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-8.6 (11.05)
CFB at Dose 7 (SAGE-217): Predose	-1.2 (9.01)
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	1.4 (10.60)
CFB at Dose 7 (SAGE-217): 2 Hours Postdose	3.5 (13.18)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-7.5 (12.79)
CFB at Day 14 (Follow-up)	0.7 (14.50)

110. Secondary Outcome

Title	CFB in Supine Diastolic Blood Pressure - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	78.2 (7.49)
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	0.7 (7.13)
CFB at Dose 1 (SAGE-217): 2 Hours Postdose	1.6 (7.20)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.6 (7.23)
CFB at Dose 2 (SAGE-217): Predose	-0.1 (10.00)
CFB at Dose 2 (SAGE-217): 1 Hour Postdose	1.9 (9.23)
CFB at Dose 2 (SAGE-217): 2 Hours Postdose	-0.5 (9.75)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	1.9 (9.07)
CFB at Dose 3 (SAGE-217): Predose	0.1 (8.54)
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-1.4 (7.39)
CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-0.9 (12.21)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	0.6 (11.15)
CFB at Dose 4 (SAGE-217): Predose	-0.3 (9.24)
CFB at Dose 4 (SAGE-217): 1 Hour Postdose	1.5 (8.29)
CFB at Dose 4 (SAGE-217): 2 Hours Postdose	0.3 (8.18)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	0.4 (9.76)
CFB at Dose 5 (SAGE-217): Predose	-1.1 (9.05)
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-0.7 (9.92)
CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-0.6 (9.44)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-0.6 (9.00)
CFB at Dose 6 (SAGE-217): Predose	-2.4 (9.24)
CFB at Dose 6 (SAGE-217): 1 Hour Postdose	1.1 (9.49)
CFB at Dose 6 (SAGE-217): 2 Hours Postdose	0.6 (9.15)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	1.9 (9.74)
CFB at Dose 7 (SAGE-217): Predose	-0.6 (9.16)
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	1.8 (10.50)
CFB at Dose 7 (SAGE-217): 2 Hours Postdose	0.2 (8.50)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	0.4 (8.93)
CFB at Day 14 (Follow-up)	0.3 (8.30)

111. Secondary Outcome

Title	CFB in Standing Diastolic Blood Pressure - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	81.9 (6.99)
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-2.0 (6.04)
CFB at Dose 1 (SAGE-217): 2 Hours Postdose	-2.4 (6.32)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-1.6 (7.17)
CFB at Dose 2 (SAGE-217): Predose	-3.9 (7.18)
CFB at Dose 2 (SAGE-217): 1 Hour Postdose	-2.4 (5.11)
CFB at Dose 2 (SAGE-217): 2 Hours Postdose	-1.5 (7.69)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	-1.9 (8.64)
CFB at Dose 3 (SAGE-217): Predose	-3.9 (8.60)
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-1.4 (9.08)
CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-1.1 (7.44)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-2.4 (7.79)
CFB at Dose 4 (SAGE-217): Predose	-2.4 (7.53)
CFB at Dose 4 (SAGE-217): 1 Hour Postdose	-4.1 (9.77)
CFB at Dose 4 (SAGE-217): 2 Hours Postdose	-2.9 (8.69)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-2.8 (9.18)
CFB at Dose 5 (SAGE-217): Predose	-5.5 (8.93)
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-1.4 (7.91)
CFB at Dose 5 (SAGE-217): 2 Hours Postdose	-3.1 (8.51)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	0.0 (10.03)
CFB at Dose 6 (SAGE-217): Predose	-4.0 (7.74)
CFB at Dose 6 (SAGE-217): 1 Hour Postdose	-1.6 (8.35)
CFB at Dose 6 (SAGE-217): 2 Hours Postdose	-2.0 (7.65)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	-2.1 (8.27)
CFB at Dose 7 (SAGE-217): Predose	-1.7 (9.21)
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-0.2 (8.86)
CFB at Dose 7 (SAGE-217): 2 Hours Postdose	0.6 (8.14)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-2.7 (8.59)
CFB at Day 14 (Follow-up)	-1.1 (9.21)

112. Secondary Outcome

Title	CFB in Pulse Oximetry - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	96.9 (1.51)
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-0.6 (1.60)
CFB at Dose 1 (SAGE-217): 2 Hours Postdose	0.0 (2.08)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.4 (1.86)
CFB at Dose 2 (SAGE-217): Predose	-0.3 (1.77)
CFB at Dose 2 (SAGE-217): 1 Hour Postdose	0.1 (1.64)
CFB at Dose 2 (SAGE-217): 2 Hours Postdose	0.1 (1.73)
CFB at Dose 2 (SAGE-217): 12 Hours Postdose	0.3 (1.38)
CFB at Dose 3 (SAGE-217): Predose	0.1 (1.51)
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	0.3 (2.02)
CFB at Dose 3 (SAGE-217): 2 Hours Postdose	-0.5 (1.87)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	0.0 (2.15)
CFB at Dose 4 (SAGE-217): Predose	-0.6 (1.69)
CFB at Dose 4 (SAGE-217): 1 Hour Postdose	0.6 (1.01)
CFB at Dose 4 (SAGE-217): 2 Hours Postdose	0.1 (1.46)
CFB at Dose 4 (SAGE-217): 12 Hours Postdose	-0.3 (2.09)
CFB at Dose 5 (SAGE-217): Predose	0.5 (1.34)
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	0.6 (1.91)
CFB at Dose 5 (SAGE-217): 2 Hours Postdose	0.0 (1.66)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	0.4 (1.55)
CFB at Dose 6 (SAGE-217): Predose	-0.2 (1.63)
CFB at Dose 6 (SAGE-217): 1 Hour Postdose	0.1 (1.33)
CFB at Dose 6 (SAGE-217): 2 Hours Postdose	0.1 (1.33)
CFB at Dose 6 (SAGE-217): 12 Hours Postdose	0.3 (1.64)
CFB at Dose 7 (SAGE-217): Predose	0.2 (1.25)
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-0.4 (1.65)
CFB at Dose 7 (SAGE-217): 2 Hours Postdose	0.0 (1.71)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	0.1 (1.79)
CFB at Day 14 (Follow-up)	0.5 (1.91)

113. Secondary Outcome

Title	CFB in ECG Mean Heart Rate - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	71.4 (10.24)
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	0.1 (5.55)
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-6.6 (7.81)
CFB at Dose 3 (SAGE-217): Predose	0.2 (6.19)
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-0.3 (5.03)
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-1.6 (9.88)
CFB at Dose 5 (SAGE-217): Predose	2.2 (6.28)
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	1.8 (7.82)
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-2.4 (9.39)
CFB at Dose 7 (SAGE-217): Predose	0.2 (6.81)
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-0.7 (6.97)
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	1.4 (6.35)
CFB at Day 14 (Follow-up)	-6.1 (8.57)

114. Secondary Outcome

Title	CFB in Aggregate PR Interval - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	174.0
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	2.5
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	0.0
CFB at Dose 3 (SAGE-217): Predose	-2.0
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-1.5
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	3.5
CFB at Dose 5 (SAGE-217): Predose	1.5
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	2.0
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-1.5
CFB at Dose 7 (SAGE-217): Predose	-2.0
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	0.0
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-1.5
CFB at Day 14 (Follow-up)	-2.5

115. Secondary Outcome

Title	CFB in Aggregate RR Interval - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	823.0
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	-19.0
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	67.5
CFB at Dose 3 (SAGE-217): Predose	-32.5
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	-10.0
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	7.0
CFB at Dose 5 (SAGE-217): Predose	-23.5
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-24.5
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	50.0
CFB at Dose 7 (SAGE-217): Predose	-16.0
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-26.0
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	16.5
CFB at Day 14 (Follow-up)	66.0

116. Secondary Outcome

Title	CFB in Aggregate QT Interval - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	374.0
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	3.5
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	10.0
CFB at Dose 3 (SAGE-217): Predose	2.0
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	3.5
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	0.0
CFB at Dose 5 (SAGE-217): Predose	-1.0
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	-5.5
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	11.0
CFB at Dose 7 (SAGE-217): Predose	-5.0
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	3.5
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	2.5
CFB at Day 14 (Follow-up)	14.0

117. Secondary Outcome

Title	CFB in Aggregate QRS Duration - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	99.5
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	0.0
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-1.0
CFB at Dose 3 (SAGE-217): Predose	-1.5
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	0.0
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-0.5
CFB at Dose 5 (SAGE-217): Predose	-1.5
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	1.5
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	-3.5
CFB at Dose 7 (SAGE-217): Predose	-0.5
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-1.0
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	-1.0
CFB at Day 14 (Follow-up)	0.5

118. Secondary Outcome

Title	CFB in Aggregate QTcF Interval - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Baseline	407.0
CFB at Dose 1 (SAGE-217): 1 Hour Postdose	3.0
CFB at Dose 1 (SAGE-217): 12 Hours Postdose	-2.5
CFB at Dose 3 (SAGE-217): Predose	0.0
CFB at Dose 3 (SAGE-217): 1 Hour Postdose	0.5
CFB at Dose 3 (SAGE-217): 12 Hours Postdose	-1.5
CFB at Dose 5 (SAGE-217): Predose	1.0
CFB at Dose 5 (SAGE-217): 1 Hour Postdose	0.0
CFB at Dose 5 (SAGE-217): 12 Hours Postdose	5.5
CFB at Dose 7 (SAGE-217): Predose	-1.0
CFB at Dose 7 (SAGE-217): 1 Hour Postdose	-2.0
CFB at Dose 7 (SAGE-217): 12 Hours Postdose	2.0
CFB at Day 14 (Follow-up)	0.5

119. Secondary Outcome

Title	Percentage of Participants With a Response of 'Yes' to Any C-SSRS Suicidal Ideation or Suicidal Behavior Item - Part B
Description	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.
Time Frame	Day 1 to Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B: Antiparkinsonian Agent(s) + SAGE-217
Arm/Group Description	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.
Measure Participants	14
Suicidal Ideation: Wish to be Dead: Pre-treatment	14.3 95.3%
Suicidal Ideation: Wish to be Dead: Post-treatment	0 0%
Suicidal Behavior: Pre-treatment	0 0%
Suicidal Behavior: Post-treatment	0 0%

Adverse Events

Time Frame	Part A: Up to 14 days; Part B: Up to 14 days
Adverse Event Reporting Description	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.
Arm/Group Title	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3		Part A: SAGE-217 Day 4 to Day 7		Part A: Follow-up		Part B: SAGE-217 Dose 1 to Dose 7		Part B: Follow-up
Arm/Group Description	Participants received levodopa as antiparkinsonian agents at the normally prescribed dosing schedule, orally for Days 1 to 3.		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.		Participants resumed levodopa as antiparkinsonian agents at the normally prescribed dosing schedule for Days 8 to 14.		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.		Participants received antiparkinsonian agent(s) at normally prescribed dosing schedule for Days 8 to 14.
All Cause Mortality
	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3		Part A: SAGE-217 Day 4 to Day 7		Part A: Follow-up		Part B: SAGE-217 Dose 1 to Dose 7		Part B: Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/14 (0%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Serious Adverse Events
	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3		Part A: SAGE-217 Day 4 to Day 7		Part A: Follow-up		Part B: SAGE-217 Dose 1 to Dose 7		Part B: Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/14 (0%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Part A: Antiparkinsonian Agent(s) Day 1 to Day 3		Part A: SAGE-217 Day 4 to Day 7		Part A: Follow-up		Part B: SAGE-217 Dose 1 to Dose 7		Part B: Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)		14/14 (100%)		2/15 (13.3%)		8/14 (57.1%)		0/14 (0%)
Blood and lymphatic system disorders
Thrombocytopenia	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Eye disorders
Photophobia	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Gastrointestinal disorders
Nausea	0/15 (0%)		3/14 (21.4%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Abdominal Distension	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Diarrhoea	0/15 (0%)		0/14 (0%)		1/15 (6.7%)		0/14 (0%)		0/14 (0%)
Dyspepsia	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Faeces soft	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Flatulence	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Haematochezia	1/15 (6.7%)		0/14 (0%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Vomiting	0/15 (0%)		0/14 (0%)		1/15 (6.7%)		0/14 (0%)		0/14 (0%)
Salivary Hypersecretion	0/15 (0%)		0/14 (0%)		0/15 (0%)		1/14 (7.1%)		0/14 (0%)
General disorders
Feeling drunk	0/15 (0%)		4/14 (28.6%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Investigations
Lipase Increased	0/15 (0%)		0/14 (0%)		1/15 (6.7%)		0/14 (0%)		0/14 (0%)
Musculoskeletal and connective tissue disorders
Pain in Extremity	1/15 (6.7%)		0/14 (0%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Limb Discomfort	0/15 (0%)		0/14 (0%)		0/15 (0%)		1/14 (7.1%)		0/14 (0%)
Myalgia	0/15 (0%)		0/14 (0%)		0/15 (0%)		1/14 (7.1%)		0/14 (0%)
Nervous system disorders
Sedation	1/15 (6.7%)		10/14 (71.4%)		0/15 (0%)		2/14 (14.3%)		0/14 (0%)
Somnolence	0/15 (0%)		6/14 (42.9%)		0/15 (0%)		2/14 (14.3%)		0/14 (0%)
Dizziness	0/15 (0%)		4/14 (28.6%)		0/15 (0%)		2/14 (14.3%)		0/14 (0%)
Myoclonus	0/15 (0%)		3/14 (21.4%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Headache	1/15 (6.7%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Amnesia	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Cognitive Disorder	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Dyskinesia	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Migraine	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Migraine with Aura	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Tremor	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Parkinson's Disease	0/15 (0%)		0/14 (0%)		0/15 (0%)		1/14 (7.1%)		0/14 (0%)
Psychiatric disorders
Panic Attack	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Anxiety	0/15 (0%)		0/14 (0%)		0/15 (0%)		1/14 (7.1%)		0/14 (0%)
Confusional State	0/15 (0%)		0/14 (0%)		0/15 (0%)		1/14 (7.1%)		0/14 (0%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Cough	0/15 (0%)		0/14 (0%)		0/15 (0%)		1/14 (7.1%)		0/14 (0%)
Skin and subcutaneous tissue disorders
Dermatitis Contact	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Vascular disorders
Orthostatic Hypotension	0/15 (0%)		2/14 (14.3%)		0/15 (0%)		0/14 (0%)		0/14 (0%)
Hypotension	0/15 (0%)		1/14 (7.1%)		0/15 (0%)		0/14 (0%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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