Trial Outcomes & Findings for A Study to Evaluate SAGE-217 in Participants With Moderate to Severe Major Depressive Disorder (NCT NCT03000530)

Last Updated: 2023-11-28

Results Overview

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 defined as an adverse event with onset after the start of study drug, or any worsening of a pre-existing medical condition/adverse event with onset after the start of study drug and until 7 days after the last dose. The analysis was performed in participants included in Part A of the study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

102 participants

Primary outcome timeframe

Day 1 up to Day 21

Results posted on

2023-11-28

Participant Flow

In Part A, 21 participants were screened; 13 received at least one dose of study drug. In Part B, 169 participants were screened; 89 received at least one dose of study drug.

Participant milestones

Participant milestones
Measure	Part A: SAGE-217 Participants received SAGE-217, 30 milligrams (mg), oral solution, once daily for 14 days, as tolerated.	Part B: Placebo Eligible participants received matching placebo capsules once daily for 14 days.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Overall Study STARTED	13	44	45
Overall Study COMPLETED	13	39	41
Overall Study NOT COMPLETED	0	5	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Part B: Placebo Eligible participants received matching placebo capsules once daily for 14 days.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Overall Study Adverse Event	0	2
Overall Study Lost to Follow-up	3	1
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

The efficacy set included all participants who were randomized and received at least one dose of the double-blind study drug and had a baseline and at least 1 post-baseline efficacy evaluation in Part B.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: Placebo n=44 Participants Eligible participants received matching placebo capsules once daily for 14 days.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.	Total n=102 Participants Total of all reporting groups
Age, Continuous	48.0 years STANDARD_DEVIATION 12.83 • n=13 Participants	38.3 years STANDARD_DEVIATION 12.15 • n=44 Participants	49.1 years STANDARD_DEVIATION 13.61 • n=45 Participants	44.3 years STANDARD_DEVIATION 13.83 • n=102 Participants
Sex: Female, Male Female	9 Participants n=13 Participants	30 Participants n=44 Participants	25 Participants n=45 Participants	64 Participants n=102 Participants
Sex: Female, Male Male	4 Participants n=13 Participants	14 Participants n=44 Participants	20 Participants n=45 Participants	38 Participants n=102 Participants
Race/Ethnicity, Customized Asian	0 Participants n=13 Participants	0 Participants n=44 Participants	1 Participants n=45 Participants	1 Participants n=102 Participants
Race/Ethnicity, Customized Black or African American	9 Participants n=13 Participants	28 Participants n=44 Participants	36 Participants n=45 Participants	73 Participants n=102 Participants
Race/Ethnicity, Customized White	4 Participants n=13 Participants	16 Participants n=44 Participants	7 Participants n=45 Participants	27 Participants n=102 Participants
Race/Ethnicity, Customized Other	0 Participants n=13 Participants	0 Participants n=44 Participants	1 Participants n=45 Participants	1 Participants n=102 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=13 Participants	7 Participants n=44 Participants	1 Participants n=45 Participants	9 Participants n=102 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	12 Participants n=13 Participants	37 Participants n=44 Participants	44 Participants n=45 Participants	93 Participants n=102 Participants
17-item Hamilton Rating Scale for Depression (HAM-D) Total Score - Part B	—	25.7 score on a scale STANDARD_DEVIATION 2.42 • n=44 Participants • The efficacy set included all participants who were randomized and received at least one dose of the double-blind study drug and had a baseline and at least 1 post-baseline efficacy evaluation in Part B.	25.2 score on a scale STANDARD_DEVIATION 2.58 • n=45 Participants • The efficacy set included all participants who were randomized and received at least one dose of the double-blind study drug and had a baseline and at least 1 post-baseline efficacy evaluation in Part B.	25.5 score on a scale STANDARD_DEVIATION 2.50 • n=89 Participants • The efficacy set included all participants who were randomized and received at least one dose of the double-blind study drug and had a baseline and at least 1 post-baseline efficacy evaluation in Part B.

PRIMARY outcome

Timeframe: Day 1 up to Day 21

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) - Part A	92.3 percentage of participants	—

PRIMARY outcome

Timeframe: Day 1 up to Day 21

Population: The safety set included all participants who received at least one dose of the study drug.

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

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Percentage of Participants With TEAEs, Graded by Severity - Part A Mild	69.2 percentage of participants	—
Percentage of Participants With TEAEs, Graded by Severity - Part A Moderate	23.1 percentage of participants	—
Percentage of Participants With TEAEs, Graded by Severity - Part A Severe	0 percentage of participants	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes and leukocytes. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Basophils - Part A Change from Baseline at Follow-up Day 21	-0.003 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.0273	—
Change From Baseline in Basophils - Part A Baseline	0.032 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.0286	—
Change From Baseline in Basophils - Part A Change from Baseline at Day 8	-0.002 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.0388	—
Change From Baseline in Basophils - Part A Change from Baseline at Day 15/ET	0.005 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.0445	—
Change From Baseline in Basophils - Part A Change from Baseline at Follow-up Day 28	-0.007 10^9 cells per liter (10^9 cells/L) Standard Deviation 0.0244	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Basophils to Leukocytes Ratio [Percentage (%)] - Part A Baseline	0.56 percentage Standard Deviation 0.323	—
Change From Baseline in Basophils to Leukocytes Ratio [Percentage (%)] - Part A Change from Baseline at Day 8	0.38 percentage Standard Deviation 1.308	—
Change From Baseline in Basophils to Leukocytes Ratio [Percentage (%)] - Part A Change from Baseline at Day 15/ET	0.13 percentage Standard Deviation 0.681	—
Change From Baseline in Basophils to Leukocytes Ratio [Percentage (%)] - Part A Change from Baseline at Follow-up Day 21	0.02 percentage Standard Deviation 0.453	—
Change From Baseline in Basophils to Leukocytes Ratio [Percentage (%)] - Part A Change from Baseline at Follow-up Day 28	-0.05 percentage Standard Deviation 0.310	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Eosinophils - Part A Baseline	0.155 10^9 cells/L Standard Deviation 0.0990	—
Change From Baseline in Eosinophils - Part A Change from Baseline at Day 8	0.031 10^9 cells/L Standard Deviation 0.0749	—
Change From Baseline in Eosinophils - Part A Change from Baseline at Day 15/ET	0.044 10^9 cells/L Standard Deviation 0.0906	—
Change From Baseline in Eosinophils - Part A Change from Baseline at Follow-up Day 21	0.018 10^9 cells/L Standard Deviation 0.0796	—
Change From Baseline in Eosinophils - Part A Change from Baseline at Follow-up Day 28	0.011 10^9 cells/L Standard Deviation 0.1030	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part A Baseline	2.20 percentage Standard Deviation 1.155	—
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part A Change from Baseline at Day 8	0.68 percentage Standard Deviation 1.174	—
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part A Change from Baseline at Day 15/ET	0.98 percentage Standard Deviation 1.438	—
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part A Change from Baseline at Follow-up Day 21	0.52 percentage Standard Deviation 1.382	—
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part A Change from Baseline at Follow-up Day 28	0.43 percentage Standard Deviation 1.865	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Hematocrit - Part A Baseline	0.419 fraction of one Standard Deviation 0.0341	—
Change From Baseline in Hematocrit - Part A Change from Baseline at Day 8	0.001 fraction of one Standard Deviation 0.0123	—
Change From Baseline in Hematocrit - Part A Change from Baseline at Day 15/ET	-0.006 fraction of one Standard Deviation 0.0203	—
Change From Baseline in Hematocrit - Part A Change from Baseline at Follow-up Day 21	-0.020 fraction of one Standard Deviation 0.0239	—
Change From Baseline in Hematocrit - Part A Change from Baseline at Follow-up Day 28	-0.017 fraction of one Standard Deviation 0.0256	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Hemoglobin - Part A Baseline	136.7 grams per liter (g/L) Standard Deviation 11.28	—
Change From Baseline in Hemoglobin - Part A Change from Baseline at Day 8	0.2 grams per liter (g/L) Standard Deviation 4.30	—
Change From Baseline in Hemoglobin - Part A Change from Baseline at Day 15/ET	-2.4 grams per liter (g/L) Standard Deviation 5.25	—
Change From Baseline in Hemoglobin - Part A Change from Baseline at Follow-up Day 21	-5.7 grams per liter (g/L) Standard Deviation 5.79	—
Change From Baseline in Hemoglobin - Part A Change from Baseline at Follow-up Day 28	-4.8 grams per liter (g/L) Standard Deviation 6.21	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Lymphocytes - Part A Baseline	2.356 10^9 cells/L Standard Deviation 0.4184	—
Change From Baseline in Lymphocytes - Part A Change from Baseline at Day 8	-0.302 10^9 cells/L Standard Deviation 0.3742	—
Change From Baseline in Lymphocytes - Part A Change from Baseline at Day 15/ET	-0.339 10^9 cells/L Standard Deviation 0.4330	—
Change From Baseline in Lymphocytes - Part A Change from Baseline at Follow-up Day 21	-0.260 10^9 cells/L Standard Deviation 0.4550	—
Change From Baseline in Lymphocytes - Part A Change from Baseline at Follow-up Day 28	-0.204 10^9 cells/L Standard Deviation 0.3183	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part A Baseline	34.89 percentage Standard Deviation 9.321	—
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part A Change from Baseline at Day 8	-1.75 percentage Standard Deviation 4.741	—
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part A Change from Baseline at Day 15/ET	-1.25 percentage Standard Deviation 7.573	—
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part A Change from Baseline at Follow-up Day 21	-1.11 percentage Standard Deviation 5.716	—
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part A Change from Baseline at Follow-up Day 28	-0.62 percentage Standard Deviation 7.047	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Monocytes - Part A Baseline	0.485 10^9 cells/L Standard Deviation 0.1785	—
Change From Baseline in Monocytes - Part A Change from Baseline at Day 8	-0.042 10^9 cells/L Standard Deviation 0.1673	—
Change From Baseline in Monocytes - Part A Change from Baseline at Day 15/ET	-0.074 10^9 cells/L Standard Deviation 0.1373	—
Change From Baseline in Monocytes - Part A Change from Baseline at Follow-up Day 21	-0.090 10^9 cells/L Standard Deviation 0.1513	—
Change From Baseline in Monocytes - Part A Change from Baseline at Follow-up Day 28	-0.103 10^9 cells/L Standard Deviation 0.1369	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part A Baseline	6.72 percentage Standard Deviation 1.263	—
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part A Change from Baseline at Day 8	0.35 percentage Standard Deviation 1.805	—
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part A Change from Baseline at Day 15/ET	-0.03 percentage Standard Deviation 1.625	—
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part A Change from Baseline at Follow-up Day 21	-0.67 percentage Standard Deviation 2.364	—
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part A Change from Baseline at Follow-up Day 28	-0.82 percentage Standard Deviation 2.403	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Neutrophils - Part A Baseline	4.126 10^9 cells/L Standard Deviation 1.7922	—
Change From Baseline in Neutrophils - Part A Change from Baseline at Day 8	-0.485 10^9 cells/L Standard Deviation 1.0690	—
Change From Baseline in Neutrophils - Part A Change from Baseline at Day 15/ET	-0.528 10^9 cells/L Standard Deviation 1.1266	—
Change From Baseline in Neutrophils - Part A Change from Baseline at Follow-up Day 21	-0.411 10^9 cells/L Standard Deviation 1.1296	—
Change From Baseline in Neutrophils - Part A Change from Baseline at Follow-up Day 28	-0.190 10^9 cells/L Standard Deviation 1.2929	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part A Baseline	55.63 percentage Standard Deviation 8.925	—
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part A Change from Baseline at Day 8	0.76 percentage Standard Deviation 5.123	—
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part A Change from Baseline at Day 15/ET	0.16 percentage Standard Deviation 8.428	—
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part A Change from Baseline at Follow-up Day 21	1.23 percentage Standard Deviation 7.037	—
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part A Change from Baseline at Follow-up Day 28	1.06 percentage Standard Deviation 8.908	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Platelets - Part A Baseline	265.5 10^9 cells/L Standard Deviation 50.99	—
Change From Baseline in Platelets - Part A Change from Baseline at Day 8	-13.4 10^9 cells/L Standard Deviation 26.77	—
Change From Baseline in Platelets - Part A Change from Baseline at Day 15/ET	-7.8 10^9 cells/L Standard Deviation 25.00	—
Change From Baseline in Platelets - Part A Change from Baseline at Follow-up Day 21	8.8 10^9 cells/L Standard Deviation 19.68	—
Change From Baseline in Platelets - Part A Change from Baseline at Follow-up Day 28	-9.9 10^9 cells/L Standard Deviation 34.29	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Erythrocytes - Part A Baseline	4.661 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.4521	—
Change From Baseline in Erythrocytes - Part A Change from Baseline at Day 8	0.021 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.1406	—
Change From Baseline in Erythrocytes - Part A Change from Baseline at Day 15/ET	-0.050 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.1920	—
Change From Baseline in Erythrocytes - Part A Change from Baseline at Follow-up Day 21	-0.198 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.2302	—
Change From Baseline in Erythrocytes - Part A Change from Baseline at Follow-up Day 28	-0.164 10^12 cells per liter (10^12 cells/L) Standard Deviation 0.2382	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Reticulocytes - Part A Baseline	51.926 10^9 cells/L Standard Deviation 21.8233	—
Change From Baseline in Reticulocytes - Part A Change from Baseline at Day 8	-3.694 10^9 cells/L Standard Deviation 22.4664	—
Change From Baseline in Reticulocytes - Part A Change from Baseline at Day 15/ET	-6.163 10^9 cells/L Standard Deviation 24.9724	—
Change From Baseline in Reticulocytes - Part A Change from Baseline at Follow-up Day 21	6.174 10^9 cells/L Standard Deviation 27.1013	—
Change From Baseline in Reticulocytes - Part A Change from Baseline at Follow-up Day 28	13.012 10^9 cells/L Standard Deviation 24.3634	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Leukocytes - Part A Baseline	7.16 10^9 cells/L Standard Deviation 2.098	—
Change From Baseline in Leukocytes - Part A Change from Baseline at Day 8	-0.82 10^9 cells/L Standard Deviation 1.446	—
Change From Baseline in Leukocytes - Part A Change from Baseline at Day 15/ET	-0.91 10^9 cells/L Standard Deviation 1.388	—
Change From Baseline in Leukocytes - Part A Change from Baseline at Follow-up Day 21	-0.75 10^9 cells/L Standard Deviation 1.331	—
Change From Baseline in Leukocytes - Part A Change from Baseline at Follow-up Day 28	-0.49 10^9 cells/L Standard Deviation 1.387	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, chloride, carbon dioxide, creatinine, potassium, protein, sodium, and urea nitrogen. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Albumin - Part A Baseline	42.8 g/L Standard Deviation 2.82	—
Change From Baseline in Albumin - Part A Change from Baseline at Day 8	-1.5 g/L Standard Deviation 2.07	—
Change From Baseline in Albumin - Part A Change from Baseline at Day 15/ET	-1.0 g/L Standard Deviation 2.45	—
Change From Baseline in Albumin - Part A Change from Baseline at Follow-up Day 21	-1.5 g/L Standard Deviation 2.57	—
Change From Baseline in Albumin - Part A Change from Baseline at Follow-up Day 28	-0.8 g/L Standard Deviation 2.34	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=10 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Alkaline Phosphatase - Part A Baseline	84.3 units per liter (U/L) Standard Deviation 43.15	—
Change From Baseline in Alkaline Phosphatase - Part A Change from Baseline at Day 8	6.1 units per liter (U/L) Standard Deviation 20.73	—
Change From Baseline in Alkaline Phosphatase - Part A Change from Baseline at Day 15/ET	16.5 units per liter (U/L) Standard Deviation 30.62	—
Change From Baseline in Alkaline Phosphatase - Part A Change from Baseline at Follow-up Day 21	2.3 units per liter (U/L) Standard Deviation 9.93	—
Change From Baseline in Alkaline Phosphatase - Part A Change from Baseline at Follow-up Day 28	2.5 units per liter (U/L) Standard Deviation 10.34	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Alanine Aminotransferase - Part A Baseline	18.8 U/L Standard Deviation 10.85	—
Change From Baseline in Alanine Aminotransferase - Part A Change from Baseline at Day 8	8.8 U/L Standard Deviation 11.31	—
Change From Baseline in Alanine Aminotransferase - Part A Change from Baseline at Day 15/ET	11.0 U/L Standard Deviation 21.63	—
Change From Baseline in Alanine Aminotransferase - Part A Change from Baseline at Follow-up Day 21	2.8 U/L Standard Deviation 7.73	—
Change From Baseline in Alanine Aminotransferase - Part A Change from Baseline at Follow-up Day 28	-1.7 U/L Standard Deviation 9.39	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Aspartate Aminotransferase - Part A Baseline	18.7 U/L Standard Deviation 8.07	—
Change From Baseline in Aspartate Aminotransferase - Part A Change from Baseline at Day 8	3.7 U/L Standard Deviation 8.63	—
Change From Baseline in Aspartate Aminotransferase - Part A Change from Baseline at Day 15/ET	5.7 U/L Standard Deviation 17.50	—
Change From Baseline in Aspartate Aminotransferase - Part A Change from Baseline at Follow-up Day 21	0.0 U/L Standard Deviation 7.59	—
Change From Baseline in Aspartate Aminotransferase - Part A Change from Baseline at Follow-up Day 28	0.5 U/L Standard Deviation 12.60	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Bilirubin - Part A Baseline	8.945 micro-moles per liter (umol/L) Standard Deviation 4.5860	—
Change From Baseline in Bilirubin - Part A Change from Baseline at Day 8	-1.052 micro-moles per liter (umol/L) Standard Deviation 2.5687	—
Change From Baseline in Bilirubin - Part A Change from Baseline at Day 15/ET	-1.973 micro-moles per liter (umol/L) Standard Deviation 2.9491	—
Change From Baseline in Bilirubin - Part A Change from Baseline at Follow-up Day 21	-1.842 micro-moles per liter (umol/L) Standard Deviation 3.7243	—
Change From Baseline in Bilirubin - Part A Change from Baseline at Follow-up Day 28	-1.184 micro-moles per liter (umol/L) Standard Deviation 2.7382	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Chloride - Part A Baseline	102.9 milli-moles per liter (mmol/L) Standard Deviation 3.07	—
Change From Baseline in Chloride - Part A Change from Baseline at Day 8	1.2 milli-moles per liter (mmol/L) Standard Deviation 2.55	—
Change From Baseline in Chloride - Part A Change from Baseline at Day 15/ET	1.5 milli-moles per liter (mmol/L) Standard Deviation 2.96	—
Change From Baseline in Chloride - Part A Change from Baseline at Follow-up Day 21	1.3 milli-moles per liter (mmol/L) Standard Deviation 1.97	—
Change From Baseline in Chloride - Part A Change from Baseline at Follow-up Day 28	1.1 milli-moles per liter (mmol/L) Standard Deviation 2.10	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Carbon Dioxide - Part A Baseline	26.4 mmol/L Standard Deviation 2.50	—
Change From Baseline in Carbon Dioxide - Part A Change from Baseline at Day 8	-1.0 mmol/L Standard Deviation 2.35	—
Change From Baseline in Carbon Dioxide - Part A Change from Baseline at Day 15/ET	-0.8 mmol/L Standard Deviation 1.63	—
Change From Baseline in Carbon Dioxide - Part A Change from Baseline at Follow-up Day 21	0.0 mmol/L Standard Deviation 2.24	—
Change From Baseline in Carbon Dioxide - Part A Change from Baseline at Follow-up Day 28	-0.5 mmol/L Standard Deviation 1.56	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Creatinine - Part A Baseline	73.848 umol/L Standard Deviation 18.2228	—
Change From Baseline in Creatinine - Part A Change from Baseline at Day 8	-0.748 umol/L Standard Deviation 6.7791	—
Change From Baseline in Creatinine - Part A Change from Baseline at Day 15/ET	0.136 umol/L Standard Deviation 8.4394	—
Change From Baseline in Creatinine - Part A Change from Baseline at Follow-up Day 21	0.952 umol/L Standard Deviation 9.4279	—
Change From Baseline in Creatinine - Part A Change from Baseline at Follow-up Day 28	0.816 umol/L Standard Deviation 7.6084	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Potassium - Part A Baseline	4.25 mmol/L Standard Deviation 0.273	—
Change From Baseline in Potassium - Part A Change from Baseline at Day 8	0.12 mmol/L Standard Deviation 0.365	—
Change From Baseline in Potassium - Part A Change from Baseline at Day 15/ET	0.02 mmol/L Standard Deviation 0.349	—
Change From Baseline in Potassium - Part A Change from Baseline at Follow-up Day 21	-0.04 mmol/L Standard Deviation 0.423	—
Change From Baseline in Potassium - Part A Change from Baseline at Follow-up Day 28	-0.10 mmol/L Standard Deviation 0.416	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Protein - Part A Baseline	71.8 g/L Standard Deviation 3.59	—
Change From Baseline in Protein - Part A Change from Baseline at Day 8	-0.6 g/L Standard Deviation 5.36	—
Change From Baseline in Protein - Part A Change from Baseline at Day 15/ET	-0.2 g/L Standard Deviation 4.85	—
Change From Baseline in Protein - Part A Change from Baseline at Follow-up Day 21	-2.5 g/L Standard Deviation 4.33	—
Change From Baseline in Protein - Part A Change from Baseline at Follow-up Day 28	-0.1 g/L Standard Deviation 3.57	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Sodium - Part A Baseline	138.5 mmol/L Standard Deviation 2.18	—
Change From Baseline in Sodium - Part A Change from Baseline at Day 8	-0.2 mmol/L Standard Deviation 2.05	—
Change From Baseline in Sodium - Part A Change from Baseline at Day 15/ET	-0.1 mmol/L Standard Deviation 2.43	—
Change From Baseline in Sodium - Part A Change from Baseline at Follow-up Day 21	0.5 mmol/L Standard Deviation 2.76	—
Change From Baseline in Sodium - Part A Change from Baseline at Follow-up Day 28	0.5 mmol/L Standard Deviation 2.90	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Urea Nitrogen - Part A Baseline	4.888 mmol/L Standard Deviation 1.4234	—
Change From Baseline in Urea Nitrogen - Part A Change from Baseline at Day 8	-0.275 mmol/L Standard Deviation 1.6435	—
Change From Baseline in Urea Nitrogen - Part A Change from Baseline at Day 15/ET	-0.412 mmol/L Standard Deviation 1.4563	—
Change From Baseline in Urea Nitrogen - Part A Change from Baseline at Follow-up Day 21	-0.357 mmol/L Standard Deviation 0.9885	—
Change From Baseline in Urea Nitrogen - Part A Change from Baseline at Follow-up Day 28	-0.741 mmol/L Standard Deviation 1.3552	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio, and prothrombin time. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Activated Partial Thromboplastin Time - Part A Baseline	28.00 seconds Interval 24.5 to 33.0	—
Change From Baseline in Activated Partial Thromboplastin Time - Part A Change from Baseline at Day 8	1.00 seconds Interval -1.0 to 171.0	—
Change From Baseline in Activated Partial Thromboplastin Time - Part A Change from Baseline at Day 15/ET	1.20 seconds Interval -2.0 to 3.0	—
Change From Baseline in Activated Partial Thromboplastin Time - Part A Change from Baseline at Follow-up Day 21	0.70 seconds Interval -2.0 to 4.0	—
Change From Baseline in Activated Partial Thromboplastin Time - Part A Change from Baseline at Follow-up Day 28	1.00 seconds Interval -2.0 to 4.0	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part A Baseline	1.02 percentage Standard Deviation 0.055	—
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part A Change from Baseline at Day 8	0.04 percentage Standard Deviation 0.087	—
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part A Change from Baseline at Day 15/ET	-0.04 percentage Standard Deviation 0.051	—
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part A Change from Baseline at Follow-up Day 21	-0.01 percentage Standard Deviation 0.049	—
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part A Change from Baseline at Follow-up Day 28	-0.02 percentage Standard Deviation 0.038	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Prothrombin Time - Part A Baseline	10.50 seconds Interval 10.1 to 13.4	—
Change From Baseline in Prothrombin Time - Part A Change from Baseline at Day 8	0.10 seconds Interval -0.4 to 3.1	—
Change From Baseline in Prothrombin Time - Part A Change from Baseline at Day 15/ET	-0.40 seconds Interval -0.9 to 0.5	—
Change From Baseline in Prothrombin Time - Part A Change from Baseline at Follow-up Day 21	-0.10 seconds Interval -1.0 to 1.3	—
Change From Baseline in Prothrombin Time - Part A Change from Baseline at Follow-up Day 28	0.00 seconds Interval -0.6 to 0.6	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in pH - Part A Baseline	6.46 pH Standard Deviation 0.803	—
Change From Baseline in pH - Part A Change from Baseline at Day 8	-0.15 pH Standard Deviation 1.049	—
Change From Baseline in pH - Part A Change from Baseline at Day 15/ET	-0.35 pH Standard Deviation 0.826	—
Change From Baseline in pH - Part A Change from Baseline at Follow-up Day 21	-0.31 pH Standard Deviation 1.407	—
Change From Baseline in pH - Part A Change from Baseline at Follow-up Day 28	-0.19 pH Standard Deviation 1.300	—

PRIMARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Specific Gravity - Part A Baseline	1.014 ratio Standard Deviation 0.0083	—
Change From Baseline in Specific Gravity - Part A Change from Baseline at Day 8	0.001 ratio Standard Deviation 0.0075	—
Change From Baseline in Specific Gravity - Part A Change from Baseline at Day 15/ET	0.000 ratio Standard Deviation 0.0066	—
Change From Baseline in Specific Gravity - Part A Change from Baseline at Follow-up Day 21	0.003 ratio Standard Deviation 0.0084	—
Change From Baseline in Specific Gravity - Part A Change from Baseline at Follow-up Day 28	-0.001 ratio Standard Deviation 0.0076	—

PRIMARY outcome

Timeframe: Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Days 8, 9, 10, 11, 12, 13 and 14 (predose, 1 hour postdose), Day 15/ET, follow-up Day 21, follow-up Day 28

Population: The safety set included all participants who received at least one dose of the study drug. Number analyzed: Number of participants in the safety set with a non-missing value at both baseline and the visit.

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part A of the study. H = Hour(s). ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A Baseline	122.8 millimeter of mercury (mmHg) Standard Deviation 15.92	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 1: 0.25 H Postdose	-1.7 millimeter of mercury (mmHg) Standard Deviation 10.82	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 1: 0.5 H Postdose	-4.2 millimeter of mercury (mmHg) Standard Deviation 9.50	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 1: 1 H Postdose	-2.4 millimeter of mercury (mmHg) Standard Deviation 13.88	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 1: 2 H Postdose	-4.9 millimeter of mercury (mmHg) Standard Deviation 13.47	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 1: 12 H Postdose	-0.8 millimeter of mercury (mmHg) Standard Deviation 12.12	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 2: Predose	-0.8 millimeter of mercury (mmHg) Standard Deviation 17.66	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 2: 0.25 H Postdose	8.2 millimeter of mercury (mmHg) Standard Deviation 17.46	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 2: 0.5 H Postdose	0.8 millimeter of mercury (mmHg) Standard Deviation 16.21	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 2: 1 H Postdose	2.3 millimeter of mercury (mmHg) Standard Deviation 16.65	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 2: 2 H Postdose	-4.7 millimeter of mercury (mmHg) Standard Deviation 13.88	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 2: 12 H Postdose	-0.5 millimeter of mercury (mmHg) Standard Deviation 12.01	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 3: Predose	-2.1 millimeter of mercury (mmHg) Standard Deviation 14.33	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 3: 0.25 H Postdose	5.8 millimeter of mercury (mmHg) Standard Deviation 15.21	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 3: 0.5 H Postdose	0.5 millimeter of mercury (mmHg) Standard Deviation 17.08	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 3: 1 H Postdose	2.5 millimeter of mercury (mmHg) Standard Deviation 13.51	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 3: 2 H Postdose	-0.8 millimeter of mercury (mmHg) Standard Deviation 16.49	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 3: 12 H Postdose	1.7 millimeter of mercury (mmHg) Standard Deviation 12.98	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 4: Predose	-0.5 millimeter of mercury (mmHg) Standard Deviation 17.70	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 4: 0.25 H Postdose	-0.4 millimeter of mercury (mmHg) Standard Deviation 15.23	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 4: 0.5 H Postdose	1.8 millimeter of mercury (mmHg) Standard Deviation 18.69	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 4: 1 H Postdose	-0.4 millimeter of mercury (mmHg) Standard Deviation 19.35	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 4: 2 H Postdose	-3.4 millimeter of mercury (mmHg) Standard Deviation 13.58	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 4: 12 H Postdose	-2.7 millimeter of mercury (mmHg) Standard Deviation 18.63	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 5: Predose	-0.1 millimeter of mercury (mmHg) Standard Deviation 20.01	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 5: 0.25 H Postdose	3.1 millimeter of mercury (mmHg) Standard Deviation 18.18	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 5: 0.5 H Postdose	0.3 millimeter of mercury (mmHg) Standard Deviation 16.94	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 5: 1 H Postdose	-4.8 millimeter of mercury (mmHg) Standard Deviation 20.99	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 5: 2 H Postdose	-2.9 millimeter of mercury (mmHg) Standard Deviation 16.11	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 5: 12 H Postdose	-1.5 millimeter of mercury (mmHg) Standard Deviation 15.90	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 6: Predose	-0.2 millimeter of mercury (mmHg) Standard Deviation 15.95	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 6: 0.25 H Postdose	-0.2 millimeter of mercury (mmHg) Standard Deviation 17.21	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 6: 0.5 H Postdose	1.8 millimeter of mercury (mmHg) Standard Deviation 14.62	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 6: 1 H Postdose	0.9 millimeter of mercury (mmHg) Standard Deviation 15.86	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 6: 2 H Postdose	-3.5 millimeter of mercury (mmHg) Standard Deviation 16.79	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 6: 12 H Postdose	-1.9 millimeter of mercury (mmHg) Standard Deviation 22.35	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 7: Predose	-1.2 millimeter of mercury (mmHg) Standard Deviation 21.17	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 7: 0.25 H Postdose	4.0 millimeter of mercury (mmHg) Standard Deviation 16.40	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 7: 0.5 H Postdose	1.5 millimeter of mercury (mmHg) Standard Deviation 17.47	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 7: 1 H Postdose	-3.2 millimeter of mercury (mmHg) Standard Deviation 19.95	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 7: 2 H Postdose	0.3 millimeter of mercury (mmHg) Standard Deviation 13.45	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 7: 12 H Postdose	-4.3 millimeter of mercury (mmHg) Standard Deviation 13.04	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 8: Predose	4.3 millimeter of mercury (mmHg) Standard Deviation 17.77	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 8: 1 H Postdose	-4.5 millimeter of mercury (mmHg) Standard Deviation 13.15	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 9: Predose	9.4 millimeter of mercury (mmHg) Standard Deviation 15.86	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 9: 1 H Postdose	3.3 millimeter of mercury (mmHg) Standard Deviation 15.54	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 10: Predose	8.4 millimeter of mercury (mmHg) Standard Deviation 14.93	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 10: 1 H Postdose	2.4 millimeter of mercury (mmHg) Standard Deviation 14.19	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 11: Predose	8.8 millimeter of mercury (mmHg) Standard Deviation 19.16	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 11: 1 H Postdose	-1.7 millimeter of mercury (mmHg) Standard Deviation 14.26	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 12: Predose	7.4 millimeter of mercury (mmHg) Standard Deviation 16.59	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 12: 1 H Postdose	-0.2 millimeter of mercury (mmHg) Standard Deviation 18.93	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 13: Predose	3.2 millimeter of mercury (mmHg) Standard Deviation 19.62	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 13: 1 H Postdose	1.3 millimeter of mercury (mmHg) Standard Deviation 16.31	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 14: Predose	-3.8 millimeter of mercury (mmHg) Standard Deviation 18.20	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 14: 1 H Postdose	-3.9 millimeter of mercury (mmHg) Standard Deviation 15.01	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Day 15/ET	3.8 millimeter of mercury (mmHg) Standard Deviation 17.10	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Follow-up Day 21	3.9 millimeter of mercury (mmHg) Standard Deviation 10.84	—
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A CFB at Follow-up Day 28	7.3 millimeter of mercury (mmHg) Standard Deviation 15.19	—

PRIMARY outcome

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A Baseline	79.4 mmHg Standard Deviation 8.84	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 1: 0.25 H Postdose	-1.1 mmHg Standard Deviation 5.50	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 1: 0.5 H Postdose	-1.6 mmHg Standard Deviation 6.27	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 1: 1 H Postdose	-2.0 mmHg Standard Deviation 7.51	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 1: 2 H Postdose	-5.2 mmHg Standard Deviation 11.69	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 1: 12 H Postdose	1.3 mmHg Standard Deviation 7.94	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 2: Predose	-3.5 mmHg Standard Deviation 9.40	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 2: 0.25 H Postdose	-0.2 mmHg Standard Deviation 8.36	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 2: 0.5 H Postdose	-2.4 mmHg Standard Deviation 7.84	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 2: 1 H Postdose	-2.5 mmHg Standard Deviation 10.52	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 2: 2 H Postdose	-5.4 mmHg Standard Deviation 11.14	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 2: 12 H Postdose	-2.4 mmHg Standard Deviation 7.94	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 3: Predose	0.3 mmHg Standard Deviation 6.94	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 3: 0.25 H Postdose	1.9 mmHg Standard Deviation 10.33	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 3: 0.5 H Postdose	0.2 mmHg Standard Deviation 9.12	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 3: 1 H Postdose	-0.2 mmHg Standard Deviation 9.13	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 3: 2 H Postdose	-3.9 mmHg Standard Deviation 10.21	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 3: 12 H Postdose	0.0 mmHg Standard Deviation 9.64	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 4: Predose	-0.8 mmHg Standard Deviation 10.94	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 4: 0.25 H Postdose	-1.1 mmHg Standard Deviation 12.13	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 4: 0.5 H Postdose	0.1 mmHg Standard Deviation 14.80	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 4: 1 H Postdose	-3.5 mmHg Standard Deviation 12.03	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 4: 2 H Postdose	-2.3 mmHg Standard Deviation 10.27	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 4: 12 H Postdose	-1.1 mmHg Standard Deviation 13.51	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 5: Predose	-1.3 mmHg Standard Deviation 13.28	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 5: 0.25 H Postdose	-1.5 mmHg Standard Deviation 11.49	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 5: 0.5 H Postdose	-1.3 mmHg Standard Deviation 12.14	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 5: 1 H Postdose	-6.0 mmHg Standard Deviation 12.64	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 5: 2 H Postdose	-4.3 mmHg Standard Deviation 12.63	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 5: 12 H Postdose	-1.1 mmHg Standard Deviation 10.16	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 6: Predose	-2.6 mmHg Standard Deviation 12.05	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 6: 0.25 H Postdose	-0.8 mmHg Standard Deviation 10.38	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 6: 0.5 H Postdose	1.8 mmHg Standard Deviation 10.30	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 6: 1 H Postdose	0.8 mmHg Standard Deviation 11.96	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 6: 2 H Postdose	-0.8 mmHg Standard Deviation 13.04	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 6: 12 H Postdose	-2.5 mmHg Standard Deviation 14.08	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 7: Predose	2.2 mmHg Standard Deviation 13.53	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 7: 0.25 H Postdose	2.0 mmHg Standard Deviation 11.31	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 7: 0.5 H Postdose	0.2 mmHg Standard Deviation 10.39	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 7: 1 H Postdose	-0.2 mmHg Standard Deviation 12.87	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 7: 2 H Postdose	-1.8 mmHg Standard Deviation 9.16	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 7: 12 H Postdose	-2.5 mmHg Standard Deviation 8.27	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 8: Predose	2.3 mmHg Standard Deviation 11.27	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 8: 1 H Postdose	-2.9 mmHg Standard Deviation 9.28	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 9: Predose	3.2 mmHg Standard Deviation 11.91	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 9: 1 H Postdose	0.5 mmHg Standard Deviation 11.72	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 10: Predose	1.6 mmHg Standard Deviation 10.02	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 10: 1 H Postdose	-3.7 mmHg Standard Deviation 9.77	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 11: Predose	5.2 mmHg Standard Deviation 10.54	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 11: 1 H Postdose	0.0 mmHg Standard Deviation 9.41	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 12: Predose	0.4 mmHg Standard Deviation 8.87	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 12: 1 H Postdose	2.1 mmHg Standard Deviation 12.11	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 13: Predose	3.2 mmHg Standard Deviation 9.86	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 13: 1 H Postdose	3.7 mmHg Standard Deviation 8.86	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 14: Predose	-1.3 mmHg Standard Deviation 10.16	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 14: 1 H Postdose	-0.2 mmHg Standard Deviation 9.08	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Day 15/ET	-0.7 mmHg Standard Deviation 8.73	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Follow-up Day 21	3.1 mmHg Standard Deviation 10.64	—
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A CFB at Follow-up Day 28	1.8 mmHg Standard Deviation 11.26	—

PRIMARY outcome

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A Baseline	126.8 mmHg Standard Deviation 15.09	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 1: 0.25 H Postdose	-0.1 mmHg Standard Deviation 9.67	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 1: 0.5 H Postdose	-3.8 mmHg Standard Deviation 8.60	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 1: 1 H Postdose	-6.5 mmHg Standard Deviation 10.94	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 1: 2 H Postdose	-3.9 mmHg Standard Deviation 8.90	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 1: 12 H Postdose	-4.2 mmHg Standard Deviation 10.40	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 2: Predose	-3.5 mmHg Standard Deviation 11.74	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 2: 0.25 H Postdose	-0.9 mmHg Standard Deviation 15.14	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 2: 0.5 H Postdose	-1.2 mmHg Standard Deviation 11.29	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 2: 1 H Postdose	-3.8 mmHg Standard Deviation 13.64	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 2: 2 H Postdose	-3.2 mmHg Standard Deviation 14.52	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 2: 12 H Postdose	-1.7 mmHg Standard Deviation 13.68	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 3: Predose	-0.5 mmHg Standard Deviation 9.57	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 3: 0.25 H Postdose	-0.4 mmHg Standard Deviation 12.39	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 3: 0.5 H Postdose	-1.2 mmHg Standard Deviation 15.23	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 3: 1 H Postdose	-0.6 mmHg Standard Deviation 15.80	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 3: 2 H Postdose	3.3 mmHg Standard Deviation 16.41	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 3: 12 H Postdose	-1.0 mmHg Standard Deviation 15.56	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 4: Predose	-1.1 mmHg Standard Deviation 15.94	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 4: 0.25 H Postdose	0.4 mmHg Standard Deviation 13.26	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 4: 0.5 H Postdose	-0.8 mmHg Standard Deviation 13.55	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 4: 1 H Postdose	-0.8 mmHg Standard Deviation 14.81	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 4: 2 H Postdose	-5.8 mmHg Standard Deviation 13.50	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 4: 12 H Postdose	-7.1 mmHg Standard Deviation 20.47	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 5: Predose	-3.8 mmHg Standard Deviation 16.67	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 5: 0.25 H Postdose	-1.9 mmHg Standard Deviation 16.51	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 5: 0.5 H Postdose	-7.0 mmHg Standard Deviation 15.51	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 5: 1 H Postdose	-7.4 mmHg Standard Deviation 13.74	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 5: 2 H Postdose	-4.4 mmHg Standard Deviation 10.26	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 5: 12 H Postdose	-7.2 mmHg Standard Deviation 17.29	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 6: Predose	-3.7 mmHg Standard Deviation 16.20	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 6: 0.25 H Postdose	1.2 mmHg Standard Deviation 12.65	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 6: 0.5 H Postdose	0.3 mmHg Standard Deviation 11.73	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 6: 1 H Postdose	-3.2 mmHg Standard Deviation 15.96	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 6: 2 H Postdose	-7.1 mmHg Standard Deviation 12.51	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 6: 12 H Postdose	-5.6 mmHg Standard Deviation 17.41	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 7: Predose	-2.2 mmHg Standard Deviation 21.07	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 7: 0.25 H Postdose	-1.8 mmHg Standard Deviation 12.25	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 7: 0.5 H Postdose	-1.0 mmHg Standard Deviation 19.46	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 7: 1 H Postdose	-6.8 mmHg Standard Deviation 12.60	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 7: 2 H Postdose	-3.6 mmHg Standard Deviation 11.35	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 7: 12 H Postdose	-5.5 mmHg Standard Deviation 14.01	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 8: Predose	1.5 mmHg Standard Deviation 12.27	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 8: 1 H Postdose	-6.6 mmHg Standard Deviation 12.91	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 9: Predose	-0.9 mmHg Standard Deviation 12.05	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 9: 1 H Postdose	-1.9 mmHg Standard Deviation 15.18	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 10: Predose	2.8 mmHg Standard Deviation 15.82	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 10: 1 H Postdose	-4.0 mmHg Standard Deviation 14.63	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 11: Predose	5.9 mmHg Standard Deviation 13.63	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 11: 1 H Postdose	-4.9 mmHg Standard Deviation 10.18	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 12: Predose	4.1 mmHg Standard Deviation 19.31	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 12: 1 H Postdose	-3.8 mmHg Standard Deviation 19.88	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 13: Predose	0.5 mmHg Standard Deviation 14.77	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 13: 1 H Postdose	0.8 mmHg Standard Deviation 13.04	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 14: Predose	-0.8 mmHg Standard Deviation 12.19	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 14: 1 H Postdose	-8.9 mmHg Standard Deviation 12.53	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Day 15/ET	-1.4 mmHg Standard Deviation 11.39	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Follow-up Day 21	7.8 mmHg Standard Deviation 14.23	—
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A CFB at Follow-up Day 28	3.8 mmHg Standard Deviation 13.53	—

PRIMARY outcome

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 6: 12 H Postdose	-4.5 mmHg Standard Deviation 9.75	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 7: Predose	-0.2 mmHg Standard Deviation 14.31	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A Baseline	83.9 mmHg Standard Deviation 8.17	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 1: 0.25 H Postdose	-0.2 mmHg Standard Deviation 7.60	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 1: 0.5 H Postdose	-1.5 mmHg Standard Deviation 6.33	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 1: 1 H Postdose	-1.8 mmHg Standard Deviation 5.10	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 1: 2 H Postdose	-1.5 mmHg Standard Deviation 9.13	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 1: 12 H Postdose	-3.5 mmHg Standard Deviation 7.49	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 2: Predose	-4.9 mmHg Standard Deviation 5.41	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 2: 0.25 H Postdose	-3.3 mmHg Standard Deviation 9.53	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 2: 0.5 H Postdose	-1.8 mmHg Standard Deviation 7.46	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 2: 1 H Postdose	-3.4 mmHg Standard Deviation 9.90	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 2: 2 H Postdose	-5.8 mmHg Standard Deviation 9.63	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 2: 12 H Postdose	-3.2 mmHg Standard Deviation 13.06	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 3: Predose	-4.2 mmHg Standard Deviation 13.31	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 3: 0.25 H Postdose	-3.6 mmHg Standard Deviation 10.79	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 3: 0.5 H Postdose	-1.9 mmHg Standard Deviation 9.84	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 3: 1 H Postdose	-0.8 mmHg Standard Deviation 9.58	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 3: 2 H Postdose	-2.2 mmHg Standard Deviation 13.80	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 3: 12 H Postdose	0.7 mmHg Standard Deviation 10.23	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 4: Predose	-0.8 mmHg Standard Deviation 13.05	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 4: 0.25 H Postdose	-1.4 mmHg Standard Deviation 10.91	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 4: 0.5 H Postdose	-2.6 mmHg Standard Deviation 11.00	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 4: 1 H Postdose	-3.3 mmHg Standard Deviation 9.02	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 4: 2 H Postdose	-2.9 mmHg Standard Deviation 10.16	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 4: 12 H Postdose	-2.6 mmHg Standard Deviation 12.31	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 5: Predose	-2.1 mmHg Standard Deviation 10.54	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 5: 0.25 H Postdose	-2.6 mmHg Standard Deviation 11.99	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 5: 0.5 H Postdose	-5.3 mmHg Standard Deviation 10.71	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 5: 1 H Postdose	-5.9 mmHg Standard Deviation 13.51	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 5: 2 H Postdose	-5.4 mmHg Standard Deviation 13.26	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 5: 12 H Postdose	-2.2 mmHg Standard Deviation 12.98	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 6: Predose	-2.2 mmHg Standard Deviation 10.86	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 6: 0.25 H Postdose	-0.9 mmHg Standard Deviation 9.27	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 6: 0.5 H Postdose	1.2 mmHg Standard Deviation 7.97	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 6: 1 H Postdose	-1.8 mmHg Standard Deviation 9.08	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 6: 2 H Postdose	-2.6 mmHg Standard Deviation 6.70	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 7: 0.25 H Postdose	0.8 mmHg Standard Deviation 9.86	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 7: 0.5 H Postdose	-0.4 mmHg Standard Deviation 12.76	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 7: 1 H Postdose	-2.5 mmHg Standard Deviation 11.33	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 7: 2 H Postdose	-2.4 mmHg Standard Deviation 7.97	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 7: 12 H Postdose	-3.0 mmHg Standard Deviation 8.23	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 8: Predose	1.3 mmHg Standard Deviation 9.91	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 8: 1 H Postdose	-4.5 mmHg Standard Deviation 11.97	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 9: Predose	-2.5 mmHg Standard Deviation 10.83	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 9: 1 H Postdose	-4.2 mmHg Standard Deviation 10.61	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 10: Predose	-2.0 mmHg Standard Deviation 9.70	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 10: 1 H Postdose	-3.7 mmHg Standard Deviation 9.64	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 11: Predose	2.0 mmHg Standard Deviation 9.03	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 11: 1 H Postdose	-7.1 mmHg Standard Deviation 8.61	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 12: Predose	-3.8 mmHg Standard Deviation 10.40	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 12: 1 H Postdose	-2.5 mmHg Standard Deviation 10.62	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 13: Predose	0.5 mmHg Standard Deviation 4.88	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 13: 1 H Postdose	1.4 mmHg Standard Deviation 7.08	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 14: Predose	-0.7 mmHg Standard Deviation 9.76	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 14: 1 H Postdose	-3.2 mmHg Standard Deviation 9.24	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Day 15/ET	0.5 mmHg Standard Deviation 8.39	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Follow-up Day 21	0.8 mmHg Standard Deviation 10.64	—
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A CFB at Follow-up Day 28	1.7 mmHg Standard Deviation 6.80	—

PRIMARY outcome

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Heart Rate - Part A Baseline	80.0 beats per minute (beats/min) Standard Deviation 13.10	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 1: 0.25 H Postdose	-2.7 beats per minute (beats/min) Standard Deviation 9.91	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 1: 0.5 H Postdose	-5.9 beats per minute (beats/min) Standard Deviation 13.44	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 1: 1 H Postdose	-4.6 beats per minute (beats/min) Standard Deviation 13.07	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 1: 2 H Postdose	-2.6 beats per minute (beats/min) Standard Deviation 14.77	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 1: 12 H Postdose	-2.2 beats per minute (beats/min) Standard Deviation 15.22	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 2: Predose	-6.6 beats per minute (beats/min) Standard Deviation 14.66	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 2: 0.25 H Postdose	-6.6 beats per minute (beats/min) Standard Deviation 13.64	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 2: 0.5 H Postdose	-6.4 beats per minute (beats/min) Standard Deviation 12.96	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 2: 1 H Postdose	-2.8 beats per minute (beats/min) Standard Deviation 16.75	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 2: 2 H Postdose	-3.5 beats per minute (beats/min) Standard Deviation 13.97	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 2: 12 H Postdose	-10.7 beats per minute (beats/min) Standard Deviation 14.68	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 3: Predose	-4.8 beats per minute (beats/min) Standard Deviation 15.82	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 3: 0.25 H Postdose	-6.1 beats per minute (beats/min) Standard Deviation 18.02	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 3: 0.5 H Postdose	-6.1 beats per minute (beats/min) Standard Deviation 14.23	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 3: 1 H Postdose	-1.2 beats per minute (beats/min) Standard Deviation 13.83	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 3: 2 H Postdose	-1.4 beats per minute (beats/min) Standard Deviation 16.19	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 3: 12 H Postdose	-8.2 beats per minute (beats/min) Standard Deviation 15.60	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 4: Predose	-6.8 beats per minute (beats/min) Standard Deviation 15.33	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 4: 0.25 H Postdose	-8.5 beats per minute (beats/min) Standard Deviation 15.58	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 4: 0.5 H Postdose	-5.3 beats per minute (beats/min) Standard Deviation 14.09	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 4: 1 H Postdose	-5.0 beats per minute (beats/min) Standard Deviation 15.46	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 4: 2 H Postdose	0.7 beats per minute (beats/min) Standard Deviation 12.21	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 4: 12 H Postdose	-5.2 beats per minute (beats/min) Standard Deviation 12.39	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 5: Predose	-5.2 beats per minute (beats/min) Standard Deviation 12.39	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 5: 0.25 H Postdose	-6.7 beats per minute (beats/min) Standard Deviation 16.93	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 5: 0.5 H Postdose	-4.4 beats per minute (beats/min) Standard Deviation 16.11	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 5: 1 H Postdose	-3.2 beats per minute (beats/min) Standard Deviation 13.57	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 5: 2 H Postdose	-1.0 beats per minute (beats/min) Standard Deviation 13.21	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 5: 12 H Postdose	-2.6 beats per minute (beats/min) Standard Deviation 14.71	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 6: Predose	-2.2 beats per minute (beats/min) Standard Deviation 13.98	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 6: 0.25 H Postdose	-4.8 beats per minute (beats/min) Standard Deviation 13.49	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 6: 0.5 H Postdose	-4.8 beats per minute (beats/min) Standard Deviation 14.90	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 6: 1 H Postdose	-0.5 beats per minute (beats/min) Standard Deviation 15.98	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 6: 2 H Postdose	-3.5 beats per minute (beats/min) Standard Deviation 13.48	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 6: 12 H Postdose	-5.8 beats per minute (beats/min) Standard Deviation 20.85	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 7: Predose	-3.0 beats per minute (beats/min) Standard Deviation 20.13	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 7: 0.25 H Postdose	-4.6 beats per minute (beats/min) Standard Deviation 16.86	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 7: 0.5 H Postdose	-6.2 beats per minute (beats/min) Standard Deviation 15.53	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 7: 1 H Postdose	-1.0 beats per minute (beats/min) Standard Deviation 16.64	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 7: 2 H Postdose	-0.1 beats per minute (beats/min) Standard Deviation 16.12	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 7: 12 H Postdose	-7.0 beats per minute (beats/min) Standard Deviation 18.16	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 8: Predose	-2.1 beats per minute (beats/min) Standard Deviation 15.74	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 8: 1 H Postdose	-1.0 beats per minute (beats/min) Standard Deviation 16.07	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 9: Predose	-0.1 beats per minute (beats/min) Standard Deviation 15.18	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 9: 1 H Postdose	0.2 beats per minute (beats/min) Standard Deviation 18.44	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 10: Predose	-1.8 beats per minute (beats/min) Standard Deviation 15.39	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 10: 1 H Postdose	0.7 beats per minute (beats/min) Standard Deviation 13.91	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 11: Predose	3.3 beats per minute (beats/min) Standard Deviation 12.80	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 11: 1 H Postdose	-5.2 beats per minute (beats/min) Standard Deviation 13.56	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 12: Predose	1.9 beats per minute (beats/min) Standard Deviation 10.30	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 12: 1 H Postdose	-1.2 beats per minute (beats/min) Standard Deviation 16.61	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 13: Predose	0.2 beats per minute (beats/min) Standard Deviation 16.69	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 13: 1 H Postdose	2.9 beats per minute (beats/min) Standard Deviation 13.76	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 14: Predose	-3.7 beats per minute (beats/min) Standard Deviation 15.16	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 14: 1 H Postdose	-2.2 beats per minute (beats/min) Standard Deviation 17.24	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Day 15/ET	-3.5 beats per minute (beats/min) Standard Deviation 16.06	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Follow-up Day 21	-6.5 beats per minute (beats/min) Standard Deviation 17.66	—
Change From Baseline (CFB) in Heart Rate - Part A CFB at Follow-up Day 28	-6.8 beats per minute (beats/min) Standard Deviation 13.53	—

PRIMARY outcome

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Respiratory Rate - Part A Baseline	16.9 breaths per minute (breaths/min) Standard Deviation 1.75	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 1: 0.25 H Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 1.45	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 1: 0.5 H Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 1.45	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 1: 1 H Postdose	0.3 breaths per minute (breaths/min) Standard Deviation 1.80	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 1: 2 H Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 1.57	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 1: 12 H Postdose	-0.1 breaths per minute (breaths/min) Standard Deviation 1.26	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 2: Predose	0.5 breaths per minute (breaths/min) Standard Deviation 1.56	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 2: 0.25 H Postdose	0.3 breaths per minute (breaths/min) Standard Deviation 2.10	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 2: 0.5 H Postdose	-0.1 breaths per minute (breaths/min) Standard Deviation 1.66	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 2: 1 H Postdose	-0.2 breaths per minute (breaths/min) Standard Deviation 1.72	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 2: 2 H Postdose	-0.5 breaths per minute (breaths/min) Standard Deviation 1.66	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 2: 12 H Postdose	-0.5 breaths per minute (breaths/min) Standard Deviation 1.71	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 3: Predose	-0.4 breaths per minute (breaths/min) Standard Deviation 1.61	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 3: 0.25 H Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 1.76	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 3: 0.5 H Postdose	-0.3 breaths per minute (breaths/min) Standard Deviation 1.65	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 3: 1 H Postdose	-0.2 breaths per minute (breaths/min) Standard Deviation 1.17	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 3: 2 H Postdose	-0.7 breaths per minute (breaths/min) Standard Deviation 1.35	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 3: 12 H Postdose	-0.1 breaths per minute (breaths/min) Standard Deviation 1.66	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 4: Predose	0.1 breaths per minute (breaths/min) Standard Deviation 1.55	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 4: 0.25 H Postdose	0.3 breaths per minute (breaths/min) Standard Deviation 1.55	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 4: 0.5 H Postdose	0.3 breaths per minute (breaths/min) Standard Deviation 1.60	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 4: 1 H Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 1.20	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 4: 2 H Postdose	0.3 breaths per minute (breaths/min) Standard Deviation 1.67	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 4: 12 H Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 1.94	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 5: Predose	0.2 breaths per minute (breaths/min) Standard Deviation 1.57	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 5: 0.25 H Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 1.39	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 5: 0.5 H Postdose	0.4 breaths per minute (breaths/min) Standard Deviation 1.50	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 5: 1 H Postdose	0.2 breaths per minute (breaths/min) Standard Deviation 1.64	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 5: 2 H Postdose	-0.5 breaths per minute (breaths/min) Standard Deviation 1.75	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 5: 12 H Postdose	-0.5 breaths per minute (breaths/min) Standard Deviation 2.99	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 6: Predose	0.2 breaths per minute (breaths/min) Standard Deviation 1.83	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 6: 0.25 H Postdose	0.2 breaths per minute (breaths/min) Standard Deviation 1.83	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 6: 0.5 H Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.89	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 6: 1 H Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 1.55	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 6: 2 H Postdose	0.1 breaths per minute (breaths/min) Standard Deviation 2.10	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 6: 12 H Postdose	-0.1 breaths per minute (breaths/min) Standard Deviation 1.12	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 7: Predose	0.1 breaths per minute (breaths/min) Standard Deviation 1.55	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 7: 0.25 H Postdose	0.8 breaths per minute (breaths/min) Standard Deviation 1.99	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 7: 0.5 H Postdose	0.2 breaths per minute (breaths/min) Standard Deviation 0.83	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 7: 1 H Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 1.85	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 7: 2 H Postdose	-0.1 breaths per minute (breaths/min) Standard Deviation 2.02	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 7: 12 H Postdose	-0.3 breaths per minute (breaths/min) Standard Deviation 2.53	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 8: Predose	1.2 breaths per minute (breaths/min) Standard Deviation 2.28	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 8: 1 H Postdose	-0.3 breaths per minute (breaths/min) Standard Deviation 1.84	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 9: Predose	0.5 breaths per minute (breaths/min) Standard Deviation 2.18	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 9: 1 H Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 2.67	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 10: Predose	0.6 breaths per minute (breaths/min) Standard Deviation 2.50	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 10: 1 H Postdose	0.0 breaths per minute (breaths/min) Standard Deviation 1.96	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 11: Predose	0.8 breaths per minute (breaths/min) Standard Deviation 1.95	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 11: 1 H Postdose	-0.2 breaths per minute (breaths/min) Standard Deviation 1.80	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 12: Predose	0.5 breaths per minute (breaths/min) Standard Deviation 1.85	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 12: 1 H Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 2.54	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 13: Predose	0.3 breaths per minute (breaths/min) Standard Deviation 2.39	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 13: 1 H Postdose	0.5 breaths per minute (breaths/min) Standard Deviation 1.00	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 14: Predose	0.3 breaths per minute (breaths/min) Standard Deviation 1.55	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 14: 1 H Postdose	0.0 breaths per minute (breaths/min) Standard Deviation 2.12	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Day 15/ET	0.1 breaths per minute (breaths/min) Standard Deviation 2.10	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Follow-up Day 21	0.8 breaths per minute (breaths/min) Standard Deviation 1.92	—
Change From Baseline (CFB) in Respiratory Rate - Part A CFB at Follow-up Day 28	0.3 breaths per minute (breaths/min) Standard Deviation 1.60	—

PRIMARY outcome

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Oral Temperature - Part A Baseline	36.71 degrees Celsius (degrees C) Standard Deviation 0.278	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 1: 0.25 H Postdose	-0.17 degrees Celsius (degrees C) Standard Deviation 0.457	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 1: 0.5 H Postdose	0.12 degrees Celsius (degrees C) Standard Deviation 0.302	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 1: 1 H Postdose	0.11 degrees Celsius (degrees C) Standard Deviation 0.468	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 1: 2 H Postdose	0.03 degrees Celsius (degrees C) Standard Deviation 0.438	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 1: 12 H Postdose	-0.09 degrees Celsius (degrees C) Standard Deviation 0.433	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 2: Predose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.410	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 2: 0.25 H Postdose	0.04 degrees Celsius (degrees C) Standard Deviation 0.532	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 2: 0.5 H Postdose	0.00 degrees Celsius (degrees C) Standard Deviation 0.493	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 2: 1 H Postdose	0.20 degrees Celsius (degrees C) Standard Deviation 0.555	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 2: 2 H Postdose	0.01 degrees Celsius (degrees C) Standard Deviation 0.497	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 2: 12 H Postdose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.399	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 3: Predose	0.02 degrees Celsius (degrees C) Standard Deviation 0.580	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 3: 0.25 H Postdose	-0.08 degrees Celsius (degrees C) Standard Deviation 0.563	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 3: 0.5 H Postdose	-0.17 degrees Celsius (degrees C) Standard Deviation 0.497	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 3: 1 H Postdose	-0.02 degrees Celsius (degrees C) Standard Deviation 0.597	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 3: 2 H Postdose	-0.11 degrees Celsius (degrees C) Standard Deviation 0.459	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 3: 12 H Postdose	-0.22 degrees Celsius (degrees C) Standard Deviation 0.389	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 4: Predose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.525	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 4: 0.25 H Postdose	0.00 degrees Celsius (degrees C) Standard Deviation 0.473	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 4: 0.5 H Postdose	0.26 degrees Celsius (degrees C) Standard Deviation 0.459	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 4: 1 H Postdose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.619	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 4: 2 H Postdose	-0.04 degrees Celsius (degrees C) Standard Deviation 0.373	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 4: 12 H Postdose	-0.11 degrees Celsius (degrees C) Standard Deviation 0.373	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 5: Predose	-0.06 degrees Celsius (degrees C) Standard Deviation 0.498	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 5: 0.25 H Postdose	0.01 degrees Celsius (degrees C) Standard Deviation 0.350	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 5: 0.5 H Postdose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.418	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 5: 1 H Postdose	-0.08 degrees Celsius (degrees C) Standard Deviation 0.458	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 5: 2 H Postdose	-0.18 degrees Celsius (degrees C) Standard Deviation 0.523	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 5: 12 H Postdose	-0.09 degrees Celsius (degrees C) Standard Deviation 0.499	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 6: Predose	0.09 degrees Celsius (degrees C) Standard Deviation 0.560	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 6: 0.25 H Postdose	0.13 degrees Celsius (degrees C) Standard Deviation 0.512	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 6: 0.5 H Postdose	-0.05 degrees Celsius (degrees C) Standard Deviation 0.405	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 6: 1 H Postdose	0.06 degrees Celsius (degrees C) Standard Deviation 0.601	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 6: 2 H Postdose	-0.12 degrees Celsius (degrees C) Standard Deviation 0.526	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 6: 12 H Postdose	-0.04 degrees Celsius (degrees C) Standard Deviation 0.566	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 7: Predose	-0.11 degrees Celsius (degrees C) Standard Deviation 0.722	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 7: 0.25 H Postdose	-0.11 degrees Celsius (degrees C) Standard Deviation 0.566	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 7: 0.5 H Postdose	-0.08 degrees Celsius (degrees C) Standard Deviation 0.639	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 7: 1 H Postdose	-0.14 degrees Celsius (degrees C) Standard Deviation 0.588	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 7: 2 H Postdose	-0.02 degrees Celsius (degrees C) Standard Deviation 0.453	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 7: 12 H Postdose	-0.10 degrees Celsius (degrees C) Standard Deviation 0.534	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 8: Predose	-0.02 degrees Celsius (degrees C) Standard Deviation 0.589	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 8: 1 H Postdose	0.02 degrees Celsius (degrees C) Standard Deviation 0.351	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 9: Predose	-0.28 degrees Celsius (degrees C) Standard Deviation 0.675	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 9: 1 H Postdose	-0.17 degrees Celsius (degrees C) Standard Deviation 0.609	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 10: Predose	-0.20 degrees Celsius (degrees C) Standard Deviation 0.471	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 10: 1 H Postdose	-0.23 degrees Celsius (degrees C) Standard Deviation 0.624	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 11: Predose	0.03 degrees Celsius (degrees C) Standard Deviation 0.483	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 11: 1 H Postdose	-0.28 degrees Celsius (degrees C) Standard Deviation 0.506	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 12: Predose	-0.18 degrees Celsius (degrees C) Standard Deviation 0.504	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 12: 1 H Postdose	-0.10 degrees Celsius (degrees C) Standard Deviation 0.512	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 13: Predose	-0.12 degrees Celsius (degrees C) Standard Deviation 0.448	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 13: 1 H Postdose	-0.23 degrees Celsius (degrees C) Standard Deviation 0.342	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 14: Predose	0.01 degrees Celsius (degrees C) Standard Deviation 0.475	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 14: 1 H Postdose	0.05 degrees Celsius (degrees C) Standard Deviation 0.570	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Day 15/ET	-0.05 degrees Celsius (degrees C) Standard Deviation 0.326	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Follow-up Day 21	-0.10 degrees Celsius (degrees C) Standard Deviation 0.372	—
Change From Baseline (CFB) in Oral Temperature - Part A CFB at Follow-up Day 28	-0.12 degrees Celsius (degrees C) Standard Deviation 0.326	—

PRIMARY outcome

Timeframe: Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Day 8 (predose, 1 hour postdose)

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=12 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Oxygen Saturation - Part A Baseline	98.6 percentage of oxygen saturation Standard Deviation 1.08	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 1: 0.25 H Postdose	0.0 percentage of oxygen saturation Standard Deviation 1.65	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 1: 0.5 H Postdose	-0.4 percentage of oxygen saturation Standard Deviation 2.02	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 1: 1 H Postdose	0.3 percentage of oxygen saturation Standard Deviation 1.22	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 1: 2 H Postdose	-0.3 percentage of oxygen saturation Standard Deviation 2.16	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 1: 12 H Postdose	0.3 percentage of oxygen saturation Standard Deviation 1.07	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 2: Predose	-0.4 percentage of oxygen saturation Standard Deviation 1.62	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 2: 0.25 H Postdose	-0.1 percentage of oxygen saturation Standard Deviation 1.83	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 2: 0.5 H Postdose	-0.3 percentage of oxygen saturation Standard Deviation 1.44	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 2: 1 H Postdose	0.1 percentage of oxygen saturation Standard Deviation 1.62	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 2: 2 H Postdose	-0.2 percentage of oxygen saturation Standard Deviation 1.34	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 2: 12 H Postdose	-0.6 percentage of oxygen saturation Standard Deviation 1.62	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 3: Predose	0.3 percentage of oxygen saturation Standard Deviation 1.60	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 3: 0.25 H Postdose	-0.9 percentage of oxygen saturation Standard Deviation 1.68	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 3: 0.5 H Postdose	-1.3 percentage of oxygen saturation Standard Deviation 2.23	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 3: 1 H Postdose	-0.3 percentage of oxygen saturation Standard Deviation 1.87	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 3: 2 H Postdose	0.1 percentage of oxygen saturation Standard Deviation 1.37	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 3: 12 H Postdose	-0.9 percentage of oxygen saturation Standard Deviation 1.68	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 4: Predose	-1.1 percentage of oxygen saturation Standard Deviation 2.23	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 4: 0.25 H Postdose	-0.2 percentage of oxygen saturation Standard Deviation 1.85	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 4: 0.5 H Postdose	-0.6 percentage of oxygen saturation Standard Deviation 2.19	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 4: 1 H Postdose	-0.5 percentage of oxygen saturation Standard Deviation 1.68	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 4: 2 H Postdose	-0.4 percentage of oxygen saturation Standard Deviation 1.50	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 4: 12 H Postdose	-0.5 percentage of oxygen saturation Standard Deviation 2.07	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 5: Predose	-0.4 percentage of oxygen saturation Standard Deviation 1.78	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 5: 0.25 H Postdose	-0.6 percentage of oxygen saturation Standard Deviation 2.11	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 5: 0.5 H Postdose	-0.2 percentage of oxygen saturation Standard Deviation 1.53	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 5: 1 H Postdose	-0.5 percentage of oxygen saturation Standard Deviation 1.88	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 5: 2 H Postdose	-0.7 percentage of oxygen saturation Standard Deviation 2.21	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 5: 12 H Postdose	-0.2 percentage of oxygen saturation Standard Deviation 1.34	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 6: Predose	-0.4 percentage of oxygen saturation Standard Deviation 1.00	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 6: 0.25 H Postdose	-0.5 percentage of oxygen saturation Standard Deviation 1.51	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 6: 0.5 H Postdose	-0.5 percentage of oxygen saturation Standard Deviation 1.98	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 6: 1 H Postdose	-0.3 percentage of oxygen saturation Standard Deviation 0.97	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 6: 2 H Postdose	-0.3 percentage of oxygen saturation Standard Deviation 1.22	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 6: 12 H Postdose	0.3 percentage of oxygen saturation Standard Deviation 1.42	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 7: Predose	-0.5 percentage of oxygen saturation Standard Deviation 1.44	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 7: 0.25 H Postdose	-0.4 percentage of oxygen saturation Standard Deviation 2.06	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 7: 0.5 H Postdose	-0.5 percentage of oxygen saturation Standard Deviation 1.51	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 7: 1 H Postdose	-1.1 percentage of oxygen saturation Standard Deviation 1.93	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 7: 2 H Postdose	-0.6 percentage of oxygen saturation Standard Deviation 1.31	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 7: 12 H Postdose	-0.5 percentage of oxygen saturation Standard Deviation 1.63	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 8: Predose	0.2 percentage of oxygen saturation Standard Deviation 1.53	—
Change From Baseline (CFB) in Oxygen Saturation - Part A CFB at Day 8: 1 H Postdose	-0.3 percentage of oxygen saturation Standard Deviation 1.82	—

PRIMARY outcome

Timeframe: Baseline, Days 1, 2, 7, 14 and follow-up Day 21

Electrocardiogram (ECG) measures included QT interval, QTc based on Fridericia formula (QTcF interval), ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in QT Interval - Part A Baseline	401.0 milliseconds (msec) Interval 383.0 to 452.0	—
Change From Baseline in QT Interval - Part A Change from Baseline at Day 1	-8.0 milliseconds (msec) Interval -51.0 to 29.0	—
Change From Baseline in QT Interval - Part A Change from Baseline at Day 2	-12.0 milliseconds (msec) Interval -67.0 to 16.0	—
Change From Baseline in QT Interval - Part A Change from Baseline at Day 7	-22.0 milliseconds (msec) Interval -52.0 to 10.0	—
Change From Baseline in QT Interval - Part A Change from Baseline at Day 14	-16.0 milliseconds (msec) Interval -113.0 to 12.0	—
Change From Baseline in QT Interval - Part A Change from Baseline at Follow-up Day 21	-17.5 milliseconds (msec) Interval -46.0 to 8.0	—

PRIMARY outcome

Timeframe: Baseline, Days 1, 2, 7, 14 and follow-up Day 21

ECG measures included QT interval, QTcF interval, ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in QTcF Interval - Part A Baseline	423.0 msec Interval 393.0 to 479.0	—
Change From Baseline in QTcF Interval - Part A Change from Baseline at Day 1	2.0 msec Interval -26.0 to 17.0	—
Change From Baseline in QTcF Interval - Part A Change from Baseline at Day 2	-5.0 msec Interval -42.0 to 29.0	—
Change From Baseline in QTcF Interval - Part A Change from Baseline at Day 7	-4.0 msec Interval -44.0 to 18.0	—
Change From Baseline in QTcF Interval - Part A Change from Baseline at Day 14	-8.0 msec Interval -92.0 to 15.0	—
Change From Baseline in QTcF Interval - Part A Change from Baseline at Follow-up Day 21	-7.0 msec Interval -26.0 to 3.0	—

PRIMARY outcome

Timeframe: Baseline, Days 1, 2, 7, 14 and follow-up Day 21

ECG measures included QT interval, QTcF interval, ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in ECG Mean Heart Rate - Part A Baseline	65.6 beats/min Standard Deviation 7.74	—
Change From Baseline in ECG Mean Heart Rate - Part A Change from Baseline at Day 1	5.8 beats/min Standard Deviation 7.83	—
Change From Baseline in ECG Mean Heart Rate - Part A Change from Baseline at Day 2	5.6 beats/min Standard Deviation 7.05	—
Change From Baseline in ECG Mean Heart Rate - Part A Change from Baseline at Day 7	8.8 beats/min Standard Deviation 9.72	—
Change From Baseline in ECG Mean Heart Rate - Part A Change from Baseline at Day 14	6.0 beats/min Standard Deviation 10.79	—
Change From Baseline in ECG Mean Heart Rate - Part A Change from Baseline at Follow-up Day 21	7.0 beats/min Standard Deviation 6.06	—

PRIMARY outcome

Timeframe: Baseline, Days 1, 2, 7, 14 and follow-up Day 21

ECG measures included QT interval, QTcF interval, ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in RR Interval - Part A Baseline	952.0 msec Interval 723.0 to 1071.0	—
Change From Baseline in RR Interval - Part A Change from Baseline at Day 1	-65.0 msec Interval -294.0 to 78.0	—
Change From Baseline in RR Interval - Part A Change from Baseline at Day 2	-45.0 msec Interval -228.0 to 61.0	—
Change From Baseline in RR Interval - Part A Change from Baseline at Day 7	-88.0 msec Interval -330.0 to 88.0	—
Change From Baseline in RR Interval - Part A Change from Baseline at Day 14	-107.0 msec Interval -363.0 to 147.0	—
Change From Baseline in RR Interval - Part A Change from Baseline at Follow-up Day 21	-97.0 msec Interval -242.0 to 39.0	—

PRIMARY outcome

Timeframe: Baseline, Days 1, 2, 7, 14 and follow-up Day 21

ECG measures included QT interval, QTcF interval, ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in PR Interval - Part A Change from Baseline at Day 7	2.0 msec Interval -58.0 to 20.0	—
Change From Baseline in PR Interval - Part A Baseline	158.0 msec Interval 150.0 to 338.0	—
Change From Baseline in PR Interval - Part A Change from Baseline at Day 1	1.0 msec Interval -84.0 to 18.0	—
Change From Baseline in PR Interval - Part A Change from Baseline at Day 2	-8.0 msec Interval -134.0 to 26.0	—
Change From Baseline in PR Interval - Part A Change from Baseline at Day 14	5.0 msec Interval -14.0 to 48.0	—
Change From Baseline in PR Interval - Part A Change from Baseline at Follow-up Day 21	-3.5 msec Interval -23.0 to 18.0	—

PRIMARY outcome

Timeframe: Baseline, Days 1, 2, 7, 14 and follow-up Day 21

ECG measures included QT interval, QTcF interval, ECG mean heart rate, RR interval, PR interval, and QRS duration. The analysis was performed in participants included in Part A of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in QRS Interval - Part A Baseline	94.0 msec Interval 81.0 to 114.0	—
Change From Baseline in QRS Interval - Part A Change from Baseline at Day 1	0.0 msec Interval -16.0 to 11.0	—
Change From Baseline in QRS Interval - Part A Change from Baseline at Day 2	-2.0 msec Interval -22.0 to 11.0	—
Change From Baseline in QRS Interval - Part A Change from Baseline at Day 7	-1.0 msec Interval -25.0 to 10.0	—
Change From Baseline in QRS Interval - Part A Change from Baseline at Day 14	4.0 msec Interval -20.0 to 16.0	—
Change From Baseline in QRS Interval - Part A Change from Baseline at Follow-up Day 21	-0.5 msec Interval -14.0 to 27.0	—

PRIMARY outcome

Timeframe: Day 1 up to Day 28

Population: The safety set included all participants who received at least one dose of the study drug.

The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and behavior 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 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 specific plan. The analysis was performed in participants included in Part A of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item - Part A	0 percentage of participants	—

PRIMARY outcome

Timeframe: Baseline, Day 15

Population: The safety set included all participants who received at least one dose of the study drug.

The SSS was 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. The analysis was performed in participants included in Part A of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Stanford Sleepiness Scale (SSS) Score at Day 15 - Part A Baseline	2.3 score on a scale Standard Deviation 1.60	—
Change From Baseline in Stanford Sleepiness Scale (SSS) Score at Day 15 - Part A Change from Baseline at Day 15	-0.6 score on a scale Standard Deviation 1.50	—

PRIMARY outcome

Timeframe: Baseline, Day 15

The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items were scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The total score could range from 0 to 52. Higher scores indicated a greater degree of depression. A negative change from baseline indicated less depression. A positive change from baseline indicated more depression. The analysis was performed in participants included in Part B of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 - Part B	-10.3 score on a scale Standard Error 1.33	-17.4 score on a scale Standard Error 1.31

SECONDARY outcome

Timeframe: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28

Population: The efficacy set included all participants who received at least one dose of the study drug and had a baseline and at least one postbaseline efficacy evaluation.

The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items were scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The total score could range from 0 to 52. Higher scores indicate a greater degree of depression. A negative change from baseline indicated less depression. A positive change from baseline indicated more depression. The analysis was performed in participants included in Part A of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=13 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Baseline	27.2 score on a scale Standard Deviation 3.06	—
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Change from Baseline at Day 2	-5.9 score on a scale Standard Deviation 4.44	—
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Change from Baseline at Day 3	-9.1 score on a scale Standard Deviation 4.82	—
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Change from Baseline at Day 4	-12.4 score on a scale Standard Deviation 5.74	—
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Change from Baseline at Day 5	-14.4 score on a scale Standard Deviation 5.68	—
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Change from Baseline at Day 6	-16.0 score on a scale Standard Deviation 5.48	—
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Change from Baseline at Day 7	-16.2 score on a scale Standard Deviation 6.01	—
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Change from Baseline at Day 8	-18.2 score on a scale Standard Deviation 5.94	—
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Change from Baseline at Day 15	-19.9 score on a scale Standard Deviation 5.78	—
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Change from Baseline at Day 21	-20.5 score on a scale Standard Deviation 7.11	—
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A Change from Baseline at Day 28	-19.7 score on a scale Standard Deviation 8.09	—

SECONDARY outcome

Timeframe: Day 1 up to Day 21

Population: The safety set included all participants who received at least one dose of the study drug.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was defined as an adverse event with onset after the start of study drug, or any worsening of a pre-existing medical condition/adverse event with onset after the start of study drug and until 7 days after the last dose. The analysis was performed in participants included in Part B of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Percentage of Participants With TEAEs - Part B	45.5 percentage of participants	53.3 percentage of participants

SECONDARY outcome

Timeframe: Day 21 up to Day 42

Population: The safety set included all participants who received at least one dose of the study drug.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAE was defined as an adverse event with onset after the start of study drug, or any worsening of a pre-existing medical condition/adverse event with onset after the start of study drug and until 7 days after the last dose. Post-TEAE period was defined as 7 days after final dose through last follow-up (Day 42). The analysis was performed in participants included in Part B of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Percentage of Participants With AEs During Post-TEAE Period	22.7 percentage of participants	8.9 percentage of participants

SECONDARY outcome

Timeframe: Day 1 up to Day 21

Population: The safety set included all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Percentage of Participants With TEAEs, Graded by Severity - Part B Moderate or Severe	5 percentage of participants	6 percentage of participants
Percentage of Participants With TEAEs, Graded by Severity - Part B Severe	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Population: The safety set included all participants who received at least one dose of the study drug. Number analyzed: Number of participants in safety set with a non-missing value at both baseline and the visit within each treatment group.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Basophils - Part B Baseline	0.038 10^9 cells/L Standard Deviation 0.0478	0.041 10^9 cells/L Standard Deviation 0.0489
Change From Baseline in Basophils - Part B Change from Baseline at Day 8	0.012 10^9 cells/L Standard Deviation 0.0495	-0.004 10^9 cells/L Standard Deviation 0.0520
Change From Baseline in Basophils - Part B Change from Baseline at Day 15/ET	0.005 10^9 cells/L Standard Deviation 0.0486	0.001 10^9 cells/L Standard Deviation 0.0359
Change From Baseline in Basophils - Part B Change from Baseline at Follow-up Day 21	0.000 10^9 cells/L Standard Deviation 0.0484	-0.013 10^9 cells/L Standard Deviation 0.0396
Change From Baseline in Basophils - Part B Change from Baseline at Follow-up Day 28	0.008 10^9 cells/L Standard Deviation 0.0497	-0.018 10^9 cells/L Standard Deviation 0.0436
Change From Baseline in Basophils - Part B Change from Baseline at Follow-up Day 35	0.008 10^9 cells/L Standard Deviation 0.0561	0.007 10^9 cells/L Standard Deviation 0.0352
Change From Baseline in Basophils - Part B Change from Baseline at Follow-up Day 42	0.011 10^9 cells/L Standard Deviation 0.0483	-0.006 10^9 cells/L Standard Deviation 0.0494

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Basophils to Leukocytes Ratio (%) - Part B Baseline	0.63 percentage Standard Deviation 0.302	0.63 percentage Standard Deviation 0.274
Change From Baseline in Basophils to Leukocytes Ratio (%) - Part B Change from Baseline at Day 8	0.11 percentage Standard Deviation 0.241	0.04 percentage Standard Deviation 0.229
Change From Baseline in Basophils to Leukocytes Ratio (%) - Part B Change from Baseline at Day 15/ET	0.05 percentage Standard Deviation 0.174	0.11 percentage Standard Deviation 0.231
Change From Baseline in Basophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 21	0.06 percentage Standard Deviation 0.227	0.02 percentage Standard Deviation 0.240
Change From Baseline in Basophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 28	0.05 percentage Standard Deviation 0.258	-0.01 percentage Standard Deviation 0.318
Change From Baseline in Basophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 35	0.04 percentage Standard Deviation 0.265	0.10 percentage Standard Deviation 0.180
Change From Baseline in Basophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 42	0.10 percentage Standard Deviation 0.240	0.07 percentage Standard Deviation 0.255

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Eosinophils - Part B Baseline	0.147 10^9 cells/L Standard Deviation 0.0818	0.126 10^9 cells/L Standard Deviation 0.0801
Change From Baseline in Eosinophils - Part B Change from Baseline at Day 8	0.004 10^9 cells/L Standard Deviation 0.0578	0.025 10^9 cells/L Standard Deviation 0.0795
Change From Baseline in Eosinophils - Part B Change from Baseline at Day 15/ET	0.027 10^9 cells/L Standard Deviation 0.0804	0.037 10^9 cells/L Standard Deviation 0.0890
Change From Baseline in Eosinophils - Part B Change from Baseline at Follow-up Day 21	0.020 10^9 cells/L Standard Deviation 0.0789	0.027 10^9 cells/L Standard Deviation 0.0696
Change From Baseline in Eosinophils - Part B Change from Baseline at Follow-up Day 28	0.022 10^9 cells/L Standard Deviation 0.0940	0.015 10^9 cells/L Standard Deviation 0.0724
Change From Baseline in Eosinophils - Part B Change from Baseline at Follow-up Day 35	0.006 10^9 cells/L Standard Deviation 0.0799	0.012 10^9 cells/L Standard Deviation 0.0760
Change From Baseline in Eosinophils - Part B Change from Baseline at Follow-up Day 42	0.017 10^9 cells/L Standard Deviation 0.0772	0.017 10^9 cells/L Standard Deviation 0.0735

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part B Baseline	1.95 percentage Standard Deviation 1.018	1.96 percentage Standard Deviation 1.267
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part B Change from Baseline at Day 8	0.15 percentage Standard Deviation 0.780	0.44 percentage Standard Deviation 1.102
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part B Change from Baseline at Day 15/ET	0.53 percentage Standard Deviation 1.042	0.60 percentage Standard Deviation 1.166
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 21	0.48 percentage Standard Deviation 1.080	0.53 percentage Standard Deviation 0.916
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 28	0.48 percentage Standard Deviation 1.221	0.39 percentage Standard Deviation 1.092
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 35	0.42 percentage Standard Deviation 0.996	0.37 percentage Standard Deviation 1.015
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 42	0.55 percentage Standard Deviation 1.089	0.46 percentage Standard Deviation 1.192

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Hematocrit - Part B Baseline	0.424 fraction of one Standard Deviation 0.0372	0.436 fraction of one Standard Deviation 0.0389
Change From Baseline in Hematocrit - Part B Change from Baseline at Day 8	-0.004 fraction of one Standard Deviation 0.0240	-0.004 fraction of one Standard Deviation 0.0281
Change From Baseline in Hematocrit - Part B Change from Baseline at Day 15/ET	-0.006 fraction of one Standard Deviation 0.0210	-0.010 fraction of one Standard Deviation 0.0230
Change From Baseline in Hematocrit - Part B Change from Baseline at Follow-up Day 21	-0.015 fraction of one Standard Deviation 0.0233	-0.020 fraction of one Standard Deviation 0.0249
Change From Baseline in Hematocrit - Part B Change from Baseline at Follow-up Day 28	-0.015 fraction of one Standard Deviation 0.0235	-0.015 fraction of one Standard Deviation 0.0220
Change From Baseline in Hematocrit - Part B Change from Baseline at Follow-up Day 35	-0.011 fraction of one Standard Deviation 0.0253	-0.015 fraction of one Standard Deviation 0.0244
Change From Baseline in Hematocrit - Part B Change from Baseline at Follow-up Day 42	-0.015 fraction of one Standard Deviation 0.0223	-0.019 fraction of one Standard Deviation 0.0245

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Hemoglobin - Part B Baseline	136.1 g/L Standard Deviation 13.79	141.0 g/L Standard Deviation 14.98
Change From Baseline in Hemoglobin - Part B Change from Baseline at Day 8	-1.3 g/L Standard Deviation 7.72	-2.3 g/L Standard Deviation 9.09
Change From Baseline in Hemoglobin - Part B Change from Baseline at Day 15/ET	-1.8 g/L Standard Deviation 6.88	-3.8 g/L Standard Deviation 7.80
Change From Baseline in Hemoglobin - Part B Change from Baseline at Follow-up Day 21	-5.2 g/L Standard Deviation 7.41	-6.6 g/L Standard Deviation 7.91
Change From Baseline in Hemoglobin - Part B Change from Baseline at Follow-up Day 28	-4.9 g/L Standard Deviation 7.44	-4.9 g/L Standard Deviation 7.29
Change From Baseline in Hemoglobin - Part B Change from Baseline at Follow-up Day 35	-3.8 g/L Standard Deviation 8.16	-5.1 g/L Standard Deviation 8.18
Change From Baseline in Hemoglobin - Part B Change from Baseline at Follow-up Day 42	-4.7 g/L Standard Deviation 6.44	-5.6 g/L Standard Deviation 8.18

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Lymphocytes - Part B Baseline	2.294 10^9 cells/L Standard Deviation 0.6093	2.162 10^9 cells/L Standard Deviation 0.6275
Change From Baseline in Lymphocytes - Part B Change from Baseline at Day 8	-0.053 10^9 cells/L Standard Deviation 0.4033	-0.054 10^9 cells/L Standard Deviation 0.4501
Change From Baseline in Lymphocytes - Part B Change from Baseline at Day 15/ET	0.066 10^9 cells/L Standard Deviation 0.5139	0.025 10^9 cells/L Standard Deviation 0.4944
Change From Baseline in Lymphocytes - Part B Change from Baseline at Follow-up Day 21	-0.106 10^9 cells/L Standard Deviation 0.5656	-0.104 10^9 cells/L Standard Deviation 0.5341
Change From Baseline in Lymphocytes - Part B Change from Baseline at Follow-up Day 28	-0.073 10^9 cells/L Standard Deviation 0.5071	-0.247 10^9 cells/L Standard Deviation 0.5428
Change From Baseline in Lymphocytes - Part B Change from Baseline at Follow-up Day 35	-0.153 10^9 cells/L Standard Deviation 0.4178	-0.209 10^9 cells/L Standard Deviation 0.5137
Change From Baseline in Lymphocytes - Part B Change from Baseline at Follow-up Day 42	-0.168 10^9 cells/L Standard Deviation 0.4661	-0.133 10^9 cells/L Standard Deviation 0.4544

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part B Baseline	33.06 percentage Standard Deviation 7.144	33.87 percentage Standard Deviation 10.189
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Day 8	-0.43 percentage Standard Deviation 6.613	1.86 percentage Standard Deviation 7.057
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Day 15/ET	1.25 percentage Standard Deviation 7.203	1.96 percentage Standard Deviation 8.304
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 21	0.04 percentage Standard Deviation 7.177	-0.13 percentage Standard Deviation 9.353
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 28	0.61 percentage Standard Deviation 9.038	-0.61 percentage Standard Deviation 9.527
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 35	-0.75 percentage Standard Deviation 7.861	-0.02 percentage Standard Deviation 8.937
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 42	0.91 percentage Standard Deviation 6.960	0.30 percentage Standard Deviation 8.641

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Monocytes - Part B Baseline	0.442 10^9 cells/L Standard Deviation 0.1206	0.438 10^9 cells/L Standard Deviation 0.1339
Change From Baseline in Monocytes - Part B Change from Baseline at Day 8	0.003 10^9 cells/L Standard Deviation 0.1209	0.035 10^9 cells/L Standard Deviation 0.1631
Change From Baseline in Monocytes - Part B Change from Baseline at Day 15/ET	0.017 10^9 cells/L Standard Deviation 0.1253	0.028 10^9 cells/L Standard Deviation 0.1185
Change From Baseline in Monocytes - Part B Change from Baseline at Follow-up Day 21	0.007 10^9 cells/L Standard Deviation 0.1063	0.025 10^9 cells/L Standard Deviation 0.1333
Change From Baseline in Monocytes - Part B Change from Baseline at Follow-up Day 28	0.045 10^9 cells/L Standard Deviation 0.1415	-0.010 10^9 cells/L Standard Deviation 0.1523
Change From Baseline in Monocytes - Part B Change from Baseline at Follow-up Day 35	0.024 10^9 cells/L Standard Deviation 0.1364	0.002 10^9 cells/L Standard Deviation 0.1381
Change From Baseline in Monocytes - Part B Change from Baseline at Follow-up Day 42	0.011 10^9 cells/L Standard Deviation 0.1050	0.004 10^9 cells/L Standard Deviation 0.1313

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 42	0.94 percentage Standard Deviation 1.270	0.74 percentage Standard Deviation 2.076
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part B Baseline	6.33 percentage Standard Deviation 1.760	6.78 percentage Standard Deviation 1.970
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Day 8	0.20 percentage Standard Deviation 1.430	0.98 percentage Standard Deviation 1.661
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Day 15/ET	0.40 percentage Standard Deviation 1.942	0.79 percentage Standard Deviation 1.617
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 21	0.57 percentage Standard Deviation 1.473	0.90 percentage Standard Deviation 2.030
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 28	0.97 percentage Standard Deviation 1.869	0.77 percentage Standard Deviation 2.562
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 35	0.66 percentage Standard Deviation 1.546	0.78 percentage Standard Deviation 2.374

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Neutrophils - Part B Baseline	4.174 10^9 cells/L Standard Deviation 1.4046	3.852 10^9 cells/L Standard Deviation 1.5129
Change From Baseline in Neutrophils - Part B Change from Baseline at Day 8	-0.100 10^9 cells/L Standard Deviation 1.1146	-0.399 10^9 cells/L Standard Deviation 1.7192
Change From Baseline in Neutrophils - Part B Change from Baseline at Day 15/ET	-0.389 10^9 cells/L Standard Deviation 1.2882	-0.406 10^9 cells/L Standard Deviation 1.2479
Change From Baseline in Neutrophils - Part B Change from Baseline at Follow-up Day 21	-0.354 10^9 cells/L Standard Deviation 1.0854	-0.280 10^9 cells/L Standard Deviation 1.3687
Change From Baseline in Neutrophils - Part B Change from Baseline at Follow-up Day 28	-0.363 10^9 cells/L Standard Deviation 1.2994	-0.454 10^9 cells/L Standard Deviation 1.3814
Change From Baseline in Neutrophils - Part B Change from Baseline at Follow-up Day 35	-0.209 10^9 cells/L Standard Deviation 1.3250	-0.494 10^9 cells/L Standard Deviation 1.0343
Change From Baseline in Neutrophils - Part B Change from Baseline at Follow-up Day 42	-0.584 10^9 cells/L Standard Deviation 1.2204	-0.323 10^9 cells/L Standard Deviation 1.4669

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part B Baseline	58.03 percentage Standard Deviation 7.850	56.76 percentage Standard Deviation 10.809
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part B Change from Baseline at Day 8	-0.03 percentage Standard Deviation 7.549	-3.32 percentage Standard Deviation 8.015
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part B Change from Baseline at Day 15/ET	-2.23 percentage Standard Deviation 8.600	-3.46 percentage Standard Deviation 9.345
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 21	-1.15 percentage Standard Deviation 8.173	-1.32 percentage Standard Deviation 10.154
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 28	-2.11 percentage Standard Deviation 10.514	-0.63 percentage Standard Deviation 11.160
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 35	-0.38 percentage Standard Deviation 9.087	-1.22 percentage Standard Deviation 9.600
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 42	-2.50 percentage Standard Deviation 7.678	-1.58 percentage Standard Deviation 9.818

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=44 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Platelets - Part B Baseline	287.0 10^9 cells/L Standard Deviation 74.33	272.2 10^9 cells/L Standard Deviation 60.08
Change From Baseline in Platelets - Part B Change from Baseline at Day 8	-8.5 10^9 cells/L Standard Deviation 42.93	-0.9 10^9 cells/L Standard Deviation 36.43
Change From Baseline in Platelets - Part B Change from Baseline at Day 15/ET	6.8 10^9 cells/L Standard Deviation 39.39	3.7 10^9 cells/L Standard Deviation 36.16
Change From Baseline in Platelets - Part B Change from Baseline at Follow-up Day 21	4.7 10^9 cells/L Standard Deviation 32.94	7.4 10^9 cells/L Standard Deviation 29.01
Change From Baseline in Platelets - Part B Change from Baseline at Follow-up Day 28	3.5 10^9 cells/L Standard Deviation 40.30	5.0 10^9 cells/L Standard Deviation 31.48
Change From Baseline in Platelets - Part B Change from Baseline at Follow-up Day 35	-4.9 10^9 cells/L Standard Deviation 43.23	-1.7 10^9 cells/L Standard Deviation 31.25
Change From Baseline in Platelets - Part B Change from Baseline at Follow-up Day 42	-1.8 10^9 cells/L Standard Deviation 48.71	-2.7 10^9 cells/L Standard Deviation 33.61

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Erythrocytes - Part B Baseline	4.811 10^12 cells/L Standard Deviation 0.4827	4.902 10^12 cells/L Standard Deviation 0.4956
Change From Baseline in Erythrocytes - Part B Change from Baseline at Day 8	-0.041 10^12 cells/L Standard Deviation 0.2802	-0.074 10^12 cells/L Standard Deviation 0.2889
Change From Baseline in Erythrocytes - Part B Change from Baseline at Day 15/ET	-0.069 10^12 cells/L Standard Deviation 0.2436	-0.128 10^12 cells/L Standard Deviation 0.2714
Change From Baseline in Erythrocytes - Part B Change from Baseline at Follow-up Day 21	-0.182 10^12 cells/L Standard Deviation 0.2841	-0.225 10^12 cells/L Standard Deviation 0.2794
Change From Baseline in Erythrocytes - Part B Change from Baseline at Follow-up Day 28	-0.176 10^12 cells/L Standard Deviation 0.2599	-0.172 10^12 cells/L Standard Deviation 0.2684
Change From Baseline in Erythrocytes - Part B Change from Baseline at Follow-up Day 35	-0.134 10^12 cells/L Standard Deviation 0.3050	-0.189 10^12 cells/L Standard Deviation 0.2675
Change From Baseline in Erythrocytes - Part B Change from Baseline at Follow-up Day 42	-0.161 10^12 cells/L Standard Deviation 0.2365	-0.202 10^12 cells/L Standard Deviation 0.3181

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET

Population: The safety set included all participants who received at least one dose of the study drug. Overall number of participants analyzed: Number of participants analyzed in this outcome measure. Number analyzed: Number of participants in the safety set with a non-missing value at both baseline and the visit within each treatment group.

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=3 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=2 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Reticulocytes - Part B Baseline	32.313 10^9 cells/L Standard Deviation 19.0547	78.735 10^9 cells/L Standard Deviation 58.5272
Change From Baseline in Reticulocytes - Part B Change from Baseline at Day 8	-19.035 10^9 cells/L Standard Deviation 12.9613	—
Change From Baseline in Reticulocytes - Part B Change from Baseline at Day 15/ET	9.240 10^9 cells/L Standard Deviation NA Standard deviation was not calculated since only one participant was analyzed.	—

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=42 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=43 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Reticulocytes to Erythrocytes Ratio (%) - Part B Baseline	1.32 percentage Standard Deviation 0.360	1.40 percentage Standard Deviation 0.517
Change From Baseline in Reticulocytes to Erythrocytes Ratio (%) - Part B Change from Baseline at Day 8	-0.02 percentage Standard Deviation 0.290	-0.07 percentage Standard Deviation 0.363
Change From Baseline in Reticulocytes to Erythrocytes Ratio (%) - Part B Change from Baseline at Day 15/ET	-0.03 percentage Standard Deviation 0.310	0.00 percentage Standard Deviation 0.372
Change From Baseline in Reticulocytes to Erythrocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 21	0.14 percentage Standard Deviation 0.352	0.05 percentage Standard Deviation 0.359
Change From Baseline in Reticulocytes to Erythrocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 28	0.17 percentage Standard Deviation 0.289	0.03 percentage Standard Deviation 0.296
Change From Baseline in Reticulocytes to Erythrocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 35	0.15 percentage Standard Deviation 0.254	0.07 percentage Standard Deviation 0.320
Change From Baseline in Reticulocytes to Erythrocytes Ratio (%) - Part B Change from Baseline at Follow-up Day 42	0.12 percentage Standard Deviation 0.227	0.03 percentage Standard Deviation 0.312

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Hematology measures included basophils, basophils to leukocytes ratio, eosinophils, eosinophils to leukocytes ratio, hematocrit, hemoglobin, lymphocytes, lymphocytes to leukocytes ratio, monocytes, monocytes to leukocytes ratio, neutrophils, neutrophils to leukocytes ratio, platelets, erythrocytes, reticulocytes, reticulocytes to erythrocytes ratio and leukocytes. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Leukocytes - Part B Baseline	7.08 10^9 cells/L Standard Deviation 1.778	6.63 10^9 cells/L Standard Deviation 1.688
Change From Baseline in Leukocytes - Part B Change from Baseline at Day 8	-0.11 10^9 cells/L Standard Deviation 1.324	-0.40 10^9 cells/L Standard Deviation 1.913
Change From Baseline in Leukocytes - Part B Change from Baseline at Day 15/ET	-0.27 10^9 cells/L Standard Deviation 1.435	-0.34 10^9 cells/L Standard Deviation 1.241
Change From Baseline in Leukocytes - Part B Change from Baseline at Follow-up Day 21	-0.41 10^9 cells/L Standard Deviation 1.258	-0.35 10^9 cells/L Standard Deviation 1.410
Change From Baseline in Leukocytes - Part B Change from Baseline at Follow-up Day 28	-0.34 10^9 cells/L Standard Deviation 1.266	-0.70 10^9 cells/L Standard Deviation 1.348
Change From Baseline in Leukocytes - Part B Change from Baseline at Follow-up Day 35	-0.32 10^9 cells/L Standard Deviation 1.355	-0.70 10^9 cells/L Standard Deviation 0.993
Change From Baseline in Leukocytes - Part B Change from Baseline at Follow-up Day 42	-0.69 10^9 cells/L Standard Deviation 1.421	-0.45 10^9 cells/L Standard Deviation 1.443

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Clinical chemistry measures included albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, calcium, chloride, carbon dioxide, creatinine, glucose, potassium, magnesium, phosphate, protein, sodium, thyrotropin, and urea nitrogen. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Albumin - Part B Baseline	44.6 g/L Standard Deviation 2.69	44.6 g/L Standard Deviation 3.30
Change From Baseline in Albumin - Part B Change from Baseline at Day 8	-1.1 g/L Standard Deviation 2.66	-0.8 g/L Standard Deviation 3.24
Change From Baseline in Albumin - Part B Change from Baseline at Day 15/ET	-0.8 g/L Standard Deviation 2.73	-0.9 g/L Standard Deviation 3.23
Change From Baseline in Albumin - Part B Change from Baseline at Follow-up Day 21	-1.1 g/L Standard Deviation 2.72	-1.4 g/L Standard Deviation 3.40
Change From Baseline in Albumin - Part B Change from Baseline at Follow-up Day 28	-0.2 g/L Standard Deviation 3.01	-0.9 g/L Standard Deviation 3.07
Change From Baseline in Albumin - Part B Change from Baseline at Follow-up Day 35	-0.5 g/L Standard Deviation 2.90	-1.0 g/L Standard Deviation 3.40
Change From Baseline in Albumin - Part B Change from Baseline at Follow-up Day 42	-0.5 g/L Standard Deviation 2.30	-0.7 g/L Standard Deviation 3.43

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Alkaline Phosphatase - Part B Baseline	80.9 U/L Standard Deviation 19.18	85.5 U/L Standard Deviation 27.97
Change From Baseline in Alkaline Phosphatase - Part B Change from Baseline at Day 8	-0.1 U/L Standard Deviation 8.95	1.3 U/L Standard Deviation 14.37
Change From Baseline in Alkaline Phosphatase - Part B Change from Baseline at Day 15/ET	1.6 U/L Standard Deviation 10.39	3.1 U/L Standard Deviation 17.84
Change From Baseline in Alkaline Phosphatase - Part B Change from Baseline at Follow-up Day 21	-0.9 U/L Standard Deviation 7.66	-2.9 U/L Standard Deviation 13.64
Change From Baseline in Alkaline Phosphatase - Part B Change from Baseline at Follow-up Day 28	-0.8 U/L Standard Deviation 8.50	-2.5 U/L Standard Deviation 11.01
Change From Baseline in Alkaline Phosphatase - Part B Change from Baseline at Follow-up Day 35	1.0 U/L Standard Deviation 8.28	-4.3 U/L Standard Deviation 8.87
Change From Baseline in Alkaline Phosphatase - Part B Change from Baseline at Follow-up Day 42	-0.4 U/L Standard Deviation 12.97	-4.4 U/L Standard Deviation 9.26

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Alanine Aminotransferase - Part B Baseline	22.9 U/L Standard Deviation 11.09	22.2 U/L Standard Deviation 9.43
Change From Baseline in Alanine Aminotransferase - Part B Change from Baseline at Day 8	4.1 U/L Standard Deviation 13.09	11.0 U/L Standard Deviation 28.79
Change From Baseline in Alanine Aminotransferase - Part B Change from Baseline at Day 15/ET	7.3 U/L Standard Deviation 22.23	9.1 U/L Standard Deviation 32.27
Change From Baseline in Alanine Aminotransferase - Part B Change from Baseline at Follow-up Day 21	3.4 U/L Standard Deviation 22.86	0.1 U/L Standard Deviation 6.50
Change From Baseline in Alanine Aminotransferase - Part B Change from Baseline at Follow-up Day 28	1.6 U/L Standard Deviation 9.57	-0.8 U/L Standard Deviation 6.21
Change From Baseline in Alanine Aminotransferase - Part B Change from Baseline at Follow-up Day 35	0.5 U/L Standard Deviation 8.55	0.5 U/L Standard Deviation 10.11
Change From Baseline in Alanine Aminotransferase - Part B Change from Baseline at Follow-up Day 42	-0.2 U/L Standard Deviation 10.12	-1.0 U/L Standard Deviation 6.30

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Aspartate Aminotransferase - Part B Baseline	23.0 U/L Standard Deviation 5.19	23.5 U/L Standard Deviation 6.49
Change From Baseline in Aspartate Aminotransferase - Part B Change from Baseline at Day 8	-0.5 U/L Standard Deviation 6.31	10.0 U/L Standard Deviation 43.42
Change From Baseline in Aspartate Aminotransferase - Part B Change from Baseline at Day 15/ET	2.2 U/L Standard Deviation 12.54	5.0 U/L Standard Deviation 27.21
Change From Baseline in Aspartate Aminotransferase - Part B Change from Baseline at Follow-up Day 21	1.4 U/L Standard Deviation 11.60	-0.1 U/L Standard Deviation 6.79
Change From Baseline in Aspartate Aminotransferase - Part B Change from Baseline at Follow-up Day 28	-0.5 U/L Standard Deviation 4.89	-0.3 U/L Standard Deviation 7.62
Change From Baseline in Aspartate Aminotransferase - Part B Change from Baseline at Follow-up Day 35	-1.2 U/L Standard Deviation 5.43	-0.5 U/L Standard Deviation 7.36
Change From Baseline in Aspartate Aminotransferase - Part B Change from Baseline at Follow-up Day 42	0.1 U/L Standard Deviation 7.03	-0.1 U/L Standard Deviation 6.40

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Bilirubin - Part B Baseline	8.157 umol/L Standard Deviation 3.5160	9.422 umol/L Standard Deviation 7.5457
Change From Baseline in Bilirubin - Part B Change from Baseline at Day 8	-1.095 umol/L Standard Deviation 2.7830	-1.670 umol/L Standard Deviation 4.7335
Change From Baseline in Bilirubin - Part B Change from Baseline at Day 15/ET	-0.652 umol/L Standard Deviation 3.3092	-1.673 umol/L Standard Deviation 3.1661
Change From Baseline in Bilirubin - Part B Change from Baseline at Follow-up Day 21	-0.453 umol/L Standard Deviation 3.7470	-0.978 umol/L Standard Deviation 3.0372
Change From Baseline in Bilirubin - Part B Change from Baseline at Follow-up Day 28	-1.049 umol/L Standard Deviation 3.0737	0.162 umol/L Standard Deviation 3.7768
Change From Baseline in Bilirubin - Part B Change from Baseline at Follow-up Day 35	-0.945 umol/L Standard Deviation 3.6470	-1.170 umol/L Standard Deviation 4.3101
Change From Baseline in Bilirubin - Part B Change from Baseline at Follow-up Day 42	-0.708 umol/L Standard Deviation 3.9947	-0.526 umol/L Standard Deviation 4.4450

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Calcium - Part B Baseline	2.359 mmol/L Standard Deviation 0.0909	2.364 mmol/L Standard Deviation 0.1517
Change From Baseline in Calcium - Part B Change from Baseline at Day 8	-0.021 mmol/L Standard Deviation 0.0911	-0.033 mmol/L Standard Deviation 0.1220
Change From Baseline in Calcium - Part B Change from Baseline at Day 15/ET	-0.019 mmol/L Standard Deviation 0.1083	-0.041 mmol/L Standard Deviation 0.1171
Change From Baseline in Calcium - Part B Change from Baseline at Follow-up Day 21	-0.038 mmol/L Standard Deviation 0.0900	-0.065 mmol/L Standard Deviation 0.1120
Change From Baseline in Calcium - Part B Change from Baseline at Follow-up Day 28	-0.035 mmol/L Standard Deviation 0.1138	-0.044 mmol/L Standard Deviation 0.0961
Change From Baseline in Calcium - Part B Change from Baseline at Follow-up Day 35	-0.038 mmol/L Standard Deviation 0.1024	-0.048 mmol/L Standard Deviation 0.1201
Change From Baseline in Calcium - Part B Change from Baseline at Follow-up Day 42	-0.041 mmol/L Standard Deviation 0.0954	-0.041 mmol/L Standard Deviation 0.1290

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Chloride - Part B Baseline	104.7 mmol/L Standard Deviation 1.87	104.4 mmol/L Standard Deviation 2.53
Change From Baseline in Chloride - Part B Change from Baseline at Day 8	-0.2 mmol/L Standard Deviation 2.49	-0.2 mmol/L Standard Deviation 2.86
Change From Baseline in Chloride - Part B Change from Baseline at Day 15/ET	-0.4 mmol/L Standard Deviation 2.10	-0.1 mmol/L Standard Deviation 2.83
Change From Baseline in Chloride - Part B Change from Baseline at Follow-up Day 21	0.8 mmol/L Standard Deviation 2.59	0.5 mmol/L Standard Deviation 2.37
Change From Baseline in Chloride - Part B Change from Baseline at Follow-up Day 28	0.6 mmol/L Standard Deviation 2.47	0.3 mmol/L Standard Deviation 3.27
Change From Baseline in Chloride - Part B Change from Baseline at Follow-up Day 35	0.0 mmol/L Standard Deviation 2.50	1.1 mmol/L Standard Deviation 2.49
Change From Baseline in Chloride - Part B Change from Baseline at Follow-up Day 42	0.4 mmol/L Standard Deviation 2.39	0.8 mmol/L Standard Deviation 2.75

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Carbon Dioxide - Part B Baseline	29.3 mmol/L Standard Deviation 2.32	28.8 mmol/L Standard Deviation 2.25
Change From Baseline in Carbon Dioxide - Part B Change from Baseline at Day 8	-1.1 mmol/L Standard Deviation 2.87	0.0 mmol/L Standard Deviation 2.61
Change From Baseline in Carbon Dioxide - Part B Change from Baseline at Day 15/ET	-0.3 mmol/L Standard Deviation 2.41	0.7 mmol/L Standard Deviation 2.32
Change From Baseline in Carbon Dioxide - Part B Change from Baseline at Follow-up Day 21	-1.1 mmol/L Standard Deviation 2.31	0.2 mmol/L Standard Deviation 2.50
Change From Baseline in Carbon Dioxide - Part B Change from Baseline at Follow-up Day 28	-1.0 mmol/L Standard Deviation 2.84	-0.5 mmol/L Standard Deviation 2.69
Change From Baseline in Carbon Dioxide - Part B Change from Baseline at Follow-up Day 35	-1.0 mmol/L Standard Deviation 2.56	-0.1 mmol/L Standard Deviation 2.68
Change From Baseline in Carbon Dioxide - Part B Change from Baseline at Follow-up Day 42	-0.8 mmol/L Standard Deviation 2.86	-0.8 mmol/L Standard Deviation 2.70

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Creatinine - Part B Baseline	76.363 umol/L Standard Deviation 16.0294	77.894 umol/L Standard Deviation 14.1946
Change From Baseline in Creatinine - Part B Change from Baseline at Day 8	0.036 umol/L Standard Deviation 7.6537	-1.710 umol/L Standard Deviation 8.0850
Change From Baseline in Creatinine - Part B Change from Baseline at Day 15/ET	1.028 umol/L Standard Deviation 9.1198	0.566 umol/L Standard Deviation 7.9601
Change From Baseline in Creatinine - Part B Change from Baseline at Follow-up Day 21	0.632 umol/L Standard Deviation 8.8186	1.495 umol/L Standard Deviation 9.8651
Change From Baseline in Creatinine - Part B Change from Baseline at Follow-up Day 28	4.462 umol/L Standard Deviation 7.4979	2.614 umol/L Standard Deviation 6.6486
Change From Baseline in Creatinine - Part B Change from Baseline at Follow-up Day 35	2.300 umol/L Standard Deviation 9.0428	1.263 umol/L Standard Deviation 14.2508
Change From Baseline in Creatinine - Part B Change from Baseline at Follow-up Day 42	1.949 umol/L Standard Deviation 8.5582	0.852 umol/L Standard Deviation 9.5738

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Glucose - Part B Baseline	5.438 mmol/L Standard Deviation 1.8453	5.114 mmol/L Standard Deviation 0.9726
Change From Baseline in Glucose - Part B Change from Baseline at Day 8	0.103 mmol/L Standard Deviation 1.4778	0.045 mmol/L Standard Deviation 1.4529
Change From Baseline in Glucose - Part B Change from Baseline at Day 15/ET	0.203 mmol/L Standard Deviation 1.5462	0.390 mmol/L Standard Deviation 1.5054
Change From Baseline in Glucose - Part B Change from Baseline at Follow-up Day 21	-0.031 mmol/L Standard Deviation 1.2125	-0.308 mmol/L Standard Deviation 1.3738
Change From Baseline in Glucose - Part B Change from Baseline at Follow-up Day 28	-0.053 mmol/L Standard Deviation 1.1142	0.166 mmol/L Standard Deviation 1.3791
Change From Baseline in Glucose - Part B Change from Baseline at Follow-up Day 35	-0.094 mmol/L Standard Deviation 1.5798	0.355 mmol/L Standard Deviation 1.6032
Change From Baseline in Glucose - Part B Change from Baseline at Follow-up Day 42	0.114 mmol/L Standard Deviation 1.3631	0.059 mmol/L Standard Deviation 1.1655

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Potassium - Part B Baseline	4.33 mmol/L Standard Deviation 0.362	4.36 mmol/L Standard Deviation 0.442
Change From Baseline in Potassium - Part B Change from Baseline at Day 8	0.05 mmol/L Standard Deviation 0.432	0.09 mmol/L Standard Deviation 0.517
Change From Baseline in Potassium - Part B Change from Baseline at Day 15/ET	0.05 mmol/L Standard Deviation 0.402	0.03 mmol/L Standard Deviation 0.408
Change From Baseline in Potassium - Part B Change from Baseline at Follow-up Day 21	0.01 mmol/L Standard Deviation 0.371	-0.01 mmol/L Standard Deviation 0.467
Change From Baseline in Potassium - Part B Change from Baseline at Follow-up Day 28	0.05 mmol/L Standard Deviation 0.342	0.00 mmol/L Standard Deviation 0.581
Change From Baseline in Potassium - Part B Change from Baseline at Follow-up Day 35	0.07 mmol/L Standard Deviation 0.351	-0.04 mmol/L Standard Deviation 0.468
Change From Baseline in Potassium - Part B Change from Baseline at Follow-up Day 42	0.04 mmol/L Standard Deviation 0.420	-0.06 mmol/L Standard Deviation 0.491

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=42 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Magnesium - Part B Baseline	0.891 mmol/L Standard Deviation 0.0772	0.879 mmol/L Standard Deviation 0.0977
Change From Baseline in Magnesium - Part B Change from Baseline at Day 8	-0.020 mmol/L Standard Deviation 0.0911	-0.011 mmol/L Standard Deviation 0.0950
Change From Baseline in Magnesium - Part B Change from Baseline at Day 15/ET	-0.025 mmol/L Standard Deviation 0.0980	-0.014 mmol/L Standard Deviation 0.1095
Change From Baseline in Magnesium - Part B Change from Baseline at Follow-up Day 21	-0.023 mmol/L Standard Deviation 0.0864	-0.025 mmol/L Standard Deviation 0.0998
Change From Baseline in Magnesium - Part B Change from Baseline at Follow-up Day 28	-0.009 mmol/L Standard Deviation 0.0996	-0.030 mmol/L Standard Deviation 0.0804
Change From Baseline in Magnesium - Part B Change from Baseline at Follow-up Day 35	-0.033 mmol/L Standard Deviation 0.0981	-0.033 mmol/L Standard Deviation 0.1046
Change From Baseline in Magnesium - Part B Change from Baseline at Follow-up Day 42	-0.012 mmol/L Standard Deviation 0.1070	-0.025 mmol/L Standard Deviation 0.0929

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=42 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Phosphate - Part B Baseline	1.245 mmol/L Standard Deviation 0.1623	1.212 mmol/L Standard Deviation 0.1359
Change From Baseline in Phosphate - Part B Change from Baseline at Day 8	0.053 mmol/L Standard Deviation 0.2050	0.048 mmol/L Standard Deviation 0.2078
Change From Baseline in Phosphate - Part B Change from Baseline at Day 15/ET	0.019 mmol/L Standard Deviation 0.1969	0.010 mmol/L Standard Deviation 0.1798
Change From Baseline in Phosphate - Part B Change from Baseline at Follow-up Day 21	-0.015 mmol/L Standard Deviation 0.1609	-0.102 mmol/L Standard Deviation 0.1652
Change From Baseline in Phosphate - Part B Change from Baseline at Follow-up Day 28	-0.022 mmol/L Standard Deviation 0.1657	-0.084 mmol/L Standard Deviation 0.2291
Change From Baseline in Phosphate - Part B Change from Baseline at Follow-up Day 35	-0.108 mmol/L Standard Deviation 0.1761	-0.120 mmol/L Standard Deviation 0.2033
Change From Baseline in Phosphate - Part B Change from Baseline at Follow-up Day 42	-0.102 mmol/L Standard Deviation 0.1600	-0.089 mmol/L Standard Deviation 0.1941

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Protein - Part B Baseline	75.0 g/L Standard Deviation 5.02	76.0 g/L Standard Deviation 5.90
Change From Baseline in Protein - Part B Change from Baseline at Day 8	-2.1 g/L Standard Deviation 4.47	-1.3 g/L Standard Deviation 5.47
Change From Baseline in Protein - Part B Change from Baseline at Day 15/ET	-1.3 g/L Standard Deviation 4.45	-1.6 g/L Standard Deviation 5.90
Change From Baseline in Protein - Part B Change from Baseline at Follow-up Day 21	-2.1 g/L Standard Deviation 4.05	-2.5 g/L Standard Deviation 5.77
Change From Baseline in Protein - Part B Change from Baseline at Follow-up Day 28	-0.9 g/L Standard Deviation 5.05	-1.9 g/L Standard Deviation 5.58
Change From Baseline in Protein - Part B Change from Baseline at Follow-up Day 35	-1.2 g/L Standard Deviation 4.61	-2.3 g/L Standard Deviation 5.72
Change From Baseline in Protein - Part B Change from Baseline at Follow-up Day 42	-1.4 g/L Standard Deviation 4.01	-2.1 g/L Standard Deviation 5.73

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Sodium - Part B Baseline	140.8 mmol/L Standard Deviation 1.78	140.5 mmol/L Standard Deviation 1.82
Change From Baseline in Sodium - Part B Change from Baseline at Day 8	-0.7 mmol/L Standard Deviation 1.74	0.1 mmol/L Standard Deviation 2.08
Change From Baseline in Sodium - Part B Change from Baseline at Day 15/ET	-0.6 mmol/L Standard Deviation 1.94	0.0 mmol/L Standard Deviation 2.60
Change From Baseline in Sodium - Part B Change from Baseline at Follow-up Day 21	0.3 mmol/L Standard Deviation 2.00	0.0 mmol/L Standard Deviation 2.33
Change From Baseline in Sodium - Part B Change from Baseline at Follow-up Day 28	-0.1 mmol/L Standard Deviation 2.14	-0.1 mmol/L Standard Deviation 2.68
Change From Baseline in Sodium - Part B Change from Baseline at Follow-up Day 35	-0.8 mmol/L Standard Deviation 2.20	0.3 mmol/L Standard Deviation 2.26
Change From Baseline in Sodium - Part B Change from Baseline at Follow-up Day 42	-0.6 mmol/L Standard Deviation 2.10	-0.1 mmol/L Standard Deviation 2.28

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Thyrotropin - Part B Change from Baseline at Day 8	0.464 milli-international units per liter Standard Deviation 0.8096	0.445 milli-international units per liter Standard Deviation 0.7181
Change From Baseline in Thyrotropin - Part B Change from Baseline at Day 15/ET	0.668 milli-international units per liter Standard Deviation 1.5106	0.315 milli-international units per liter Standard Deviation 0.6782
Change From Baseline in Thyrotropin - Part B Change from Baseline at Follow-up Day 21	-0.011 milli-international units per liter Standard Deviation 0.7579	-0.014 milli-international units per liter Standard Deviation 0.7316
Change From Baseline in Thyrotropin - Part B Change from Baseline at Follow-up Day 28	0.218 milli-international units per liter Standard Deviation 0.8047	0.099 milli-international units per liter Standard Deviation 0.6297
Change From Baseline in Thyrotropin - Part B Change from Baseline at Follow-up Day 35	0.156 milli-international units per liter Standard Deviation 0.7314	0.103 milli-international units per liter Standard Deviation 0.5723
Change From Baseline in Thyrotropin - Part B Change from Baseline at Follow-up Day 42	0.156 milli-international units per liter Standard Deviation 1.0520	0.124 milli-international units per liter Standard Deviation 0.5530
Change From Baseline in Thyrotropin - Part B Baseline	1.328 milli-international units per liter Standard Deviation 0.7996	1.398 milli-international units per liter Standard Deviation 0.9451

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Urea Nitrogen - Part B Baseline	4.186 mmol/L Standard Deviation 1.4151	4.644 mmol/L Standard Deviation 2.0582
Change From Baseline in Urea Nitrogen - Part B Change from Baseline at Day 8	0.322 mmol/L Standard Deviation 1.0179	0.334 mmol/L Standard Deviation 1.6435
Change From Baseline in Urea Nitrogen - Part B Change from Baseline at Day 15/ET	0.330 mmol/L Standard Deviation 1.2817	0.189 mmol/L Standard Deviation 1.6860
Change From Baseline in Urea Nitrogen - Part B Change from Baseline at Follow-up Day 21	-0.096 mmol/L Standard Deviation 1.1059	0.196 mmol/L Standard Deviation 1.0191
Change From Baseline in Urea Nitrogen - Part B Change from Baseline at Follow-up Day 28	0.057 mmol/L Standard Deviation 1.2372	0.186 mmol/L Standard Deviation 1.0919
Change From Baseline in Urea Nitrogen - Part B Change from Baseline at Follow-up Day 35	0.138 mmol/L Standard Deviation 1.0796	0.078 mmol/L Standard Deviation 1.4422
Change From Baseline in Urea Nitrogen - Part B Change from Baseline at Follow-up Day 42	0.057 mmol/L Standard Deviation 1.2051	-0.275 mmol/L Standard Deviation 1.1708

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Activated Partial Thromboplastin Time - Part B Baseline	27.60 sec Interval 24.0 to 32.4	27.80 sec Interval 23.6 to 33.0
Change From Baseline in Activated Partial Thromboplastin Time - Part B Change from Baseline at Day 8	0.20 sec Interval -5.1 to 24.2	-0.20 sec Interval -2.8 to 4.5
Change From Baseline in Activated Partial Thromboplastin Time - Part B Change from Baseline at Day 15/ET	0.10 sec Interval -3.5 to 3.6	0.40 sec Interval -3.0 to 6.4
Change From Baseline in Activated Partial Thromboplastin Time - Part B Change from Baseline at Follow-up Day 21	0.40 sec Interval -4.2 to 3.0	0.05 sec Interval -3.5 to 3.3
Change From Baseline in Activated Partial Thromboplastin Time - Part B Change from Baseline at Follow-up Day 28	0.40 sec Interval -3.1 to 2.6	0.30 sec Interval -2.1 to 3.8
Change From Baseline in Activated Partial Thromboplastin Time - Part B Change from Baseline at Follow-up Day 35	0.10 sec Interval -2.9 to 4.1	-0.25 sec Interval -4.1 to 3.5
Change From Baseline in Activated Partial Thromboplastin Time - Part B Change from Baseline at Follow-up Day 42	0.30 sec Interval -3.1 to 4.5	0.20 sec Interval -3.5 to 6.2

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part B Baseline	1.006 percentage Standard Deviation 0.0394	1.032 percentage Standard Deviation 0.0527
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part B Change from Baseline at Day 8	0.011 percentage Standard Deviation 0.0466	-0.016 percentage Standard Deviation 0.0436
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part B Change from Baseline at Day 15/ET	-0.003 percentage Standard Deviation 0.0426	-0.010 percentage Standard Deviation 0.0628
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part B Change from Baseline at Follow-up Day 21	0.002 percentage Standard Deviation 0.0380	-0.003 percentage Standard Deviation 0.0372
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part B Change from Baseline at Follow-up Day 28	-0.007 percentage Standard Deviation 0.0337	0.002 percentage Standard Deviation 0.0440
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part B Change from Baseline at Follow-up Day 35	-0.002 percentage Standard Deviation 0.0439	-0.005 percentage Standard Deviation 0.0384
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part B Change from Baseline at Follow-up Day 42	0.002 percentage Standard Deviation 0.0390	0.003 percentage Standard Deviation 0.0420

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Prothrombin Time - Part B Baseline	10.40 sec Interval 9.7 to 11.4	10.60 sec Interval 9.9 to 12.2
Change From Baseline in Prothrombin Time - Part B Change from Baseline at Day 8	0.00 sec Interval -0.7 to 2.0	-0.20 sec Interval -1.0 to 0.7
Change From Baseline in Prothrombin Time - Part B Change from Baseline at Day 15/ET	0.00 sec Interval -1.1 to 1.0	-0.20 sec Interval -1.0 to 2.6
Change From Baseline in Prothrombin Time - Part B Change from Baseline at Follow-up Day 21	0.10 sec Interval -1.0 to 0.8	-0.10 sec Interval -0.8 to 0.7
Change From Baseline in Prothrombin Time - Part B Change from Baseline at Follow-up Day 28	-0.10 sec Interval -0.8 to 0.8	0.10 sec Interval -1.0 to 1.6
Change From Baseline in Prothrombin Time - Part B Change from Baseline at Follow-up Day 35	0.00 sec Interval -1.0 to 1.4	0.05 sec Interval -0.8 to 0.6
Change From Baseline in Prothrombin Time - Part B Change from Baseline at Follow-up Day 42	0.10 sec Interval -0.7 to 0.8	0.00 sec Interval -0.8 to 1.2

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in pH - Part B Baseline	6.22 pH Standard Deviation 0.879	6.23 pH Standard Deviation 0.857
Change From Baseline in pH - Part B Change from Baseline at Day 8	-0.32 pH Standard Deviation 0.923	-0.16 pH Standard Deviation 1.169
Change From Baseline in pH - Part B Change from Baseline at Day 15/ET	-0.37 pH Standard Deviation 0.877	-0.23 pH Standard Deviation 0.909
Change From Baseline in pH - Part B Change from Baseline at Follow-up Day 21	-0.32 pH Standard Deviation 0.940	-0.15 pH Standard Deviation 0.852
Change From Baseline in pH - Part B Change from Baseline at Follow-up Day 28	-0.27 pH Standard Deviation 0.945	-0.31 pH Standard Deviation 1.065
Change From Baseline in pH - Part B Change from Baseline at Follow-up Day 35	-0.01 pH Standard Deviation 1.275	-0.17 pH Standard Deviation 0.933
Change From Baseline in pH - Part B Change from Baseline at Follow-up Day 42	-0.12 pH Standard Deviation 1.109	-0.42 pH Standard Deviation 0.962

SECONDARY outcome

Timeframe: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42

Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in Specific Gravity - Part B Baseline	1.016 ratio Standard Deviation 0.0086	1.018 ratio Standard Deviation 0.0092
Change From Baseline in Specific Gravity - Part B Change from Baseline at Day 8	0.002 ratio Standard Deviation 0.0092	0.000 ratio Standard Deviation 0.0090
Change From Baseline in Specific Gravity - Part B Change from Baseline at Day 15/ET	0.003 ratio Standard Deviation 0.0092	-0.001 ratio Standard Deviation 0.0106
Change From Baseline in Specific Gravity - Part B Change from Baseline at Follow-up Day 21	0.003 ratio Standard Deviation 0.0101	0.000 ratio Standard Deviation 0.0094
Change From Baseline in Specific Gravity - Part B Change from Baseline at Follow-up Day 28	0.004 ratio Standard Deviation 0.0093	0.002 ratio Standard Deviation 0.0087
Change From Baseline in Specific Gravity - Part B Change from Baseline at Follow-up Day 35	0.001 ratio Standard Deviation 0.0096	0.001 ratio Standard Deviation 0.0099
Change From Baseline in Specific Gravity - Part B Change from Baseline at Follow-up Day 42	0.004 ratio Standard Deviation 0.0086	0.002 ratio Standard Deviation 0.0112

SECONDARY outcome

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part B of the study. H = Hour(s). ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 4: Predose	1.1 mmHg Standard Deviation 13.77	0.6 mmHg Standard Deviation 12.38
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B Baseline	120.5 mmHg Standard Deviation 15.41	120.6 mmHg Standard Deviation 13.95
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 1: 0.25 H Postdose	1.7 mmHg Standard Deviation 9.33	0.6 mmHg Standard Deviation 9.57
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 1: 0.5 H Postdose	1.3 mmHg Standard Deviation 8.38	0.7 mmHg Standard Deviation 10.38
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 1: 1 H Postdose	1.1 mmHg Standard Deviation 8.63	-0.3 mmHg Standard Deviation 11.09
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 1: 2 H Postdose	2.3 mmHg Standard Deviation 11.51	-0.5 mmHg Standard Deviation 11.92
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 1: 12 H Postdose	0.0 mmHg Standard Deviation 12.72	-1.5 mmHg Standard Deviation 10.58
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 2: Predose	-0.3 mmHg Standard Deviation 10.62	-0.9 mmHg Standard Deviation 10.72
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 2: 0.25 H Postdose	2.7 mmHg Standard Deviation 12.88	0.9 mmHg Standard Deviation 12.39
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 2: 0.5 H Postdose	1.9 mmHg Standard Deviation 9.49	0.2 mmHg Standard Deviation 13.18
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 2: 1 H Postdose	2.2 mmHg Standard Deviation 10.83	-0.5 mmHg Standard Deviation 11.19
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 2: 2 H Postdose	1.7 mmHg Standard Deviation 11.72	-0.2 mmHg Standard Deviation 12.39
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 2: 12 H Postdose	-1.2 mmHg Standard Deviation 11.11	-1.4 mmHg Standard Deviation 12.55
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 3: Predose	1.3 mmHg Standard Deviation 10.50	-0.1 mmHg Standard Deviation 12.61
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 3: 0.25 H Postdose	2.4 mmHg Standard Deviation 10.49	0.4 mmHg Standard Deviation 12.37
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 3: 0.5 H Postdose	3.4 mmHg Standard Deviation 13.80	-0.9 mmHg Standard Deviation 13.55
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 3: 1 H Postdose	2.2 mmHg Standard Deviation 10.18	-0.3 mmHg Standard Deviation 12.76
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 3: 2 H Postdose	1.5 mmHg Standard Deviation 12.35	-0.2 mmHg Standard Deviation 14.21
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 3: 12 H Postdose	-2.7 mmHg Standard Deviation 13.22	-3.9 mmHg Standard Deviation 12.84
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 4: 0.25 H Postdose	1.3 mmHg Standard Deviation 11.83	2.8 mmHg Standard Deviation 11.28
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 4: 0.5 H Postdose	2.2 mmHg Standard Deviation 12.29	0.7 mmHg Standard Deviation 10.42
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 4: 1 H Postdose	-0.5 mmHg Standard Deviation 11.88	0.4 mmHg Standard Deviation 11.41
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 4: 2 H Postdose	-1.4 mmHg Standard Deviation 13.06	0.3 mmHg Standard Deviation 12.84
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 4: 12 H Postdose	-2.8 mmHg Standard Deviation 14.65	-0.1 mmHg Standard Deviation 14.51
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 5: Predose	-1.9 mmHg Standard Deviation 12.82	1.0 mmHg Standard Deviation 13.67
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 5: 0.25 H Postdose	-0.8 mmHg Standard Deviation 11.60	2.6 mmHg Standard Deviation 11.60
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 5: 0.5 H Postdose	0.3 mmHg Standard Deviation 14.05	1.2 mmHg Standard Deviation 9.26
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 5: 1 H Postdose	-0.4 mmHg Standard Deviation 10.26	2.3 mmHg Standard Deviation 11.04
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 5: 2 H Postdose	0.8 mmHg Standard Deviation 10.42	-2.4 mmHg Standard Deviation 10.78
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 5: 12 H Postdose	-1.7 mmHg Standard Deviation 13.79	-1.8 mmHg Standard Deviation 12.13
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 6: Predose	0.5 mmHg Standard Deviation 13.69	5.3 mmHg Standard Deviation 13.08
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 6: 0.25 H Postdose	0.9 mmHg Standard Deviation 12.24	6.3 mmHg Standard Deviation 10.66
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 6: 0.5 H Postdose	-0.4 mmHg Standard Deviation 13.01	4.3 mmHg Standard Deviation 12.23
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 6: 1 H Postdose	0.5 mmHg Standard Deviation 12.91	4.7 mmHg Standard Deviation 12.07
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 6: 2 H Postdose	2.6 mmHg Standard Deviation 16.10	3.9 mmHg Standard Deviation 14.18
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 6: 12 H Postdose	-1.6 mmHg Standard Deviation 11.10	-0.2 mmHg Standard Deviation 12.90
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 7: Predose	-1.0 mmHg Standard Deviation 12.54	3.2 mmHg Standard Deviation 11.76
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 7: 0.25 H Postdose	0.5 mmHg Standard Deviation 14.43	1.8 mmHg Standard Deviation 10.44
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 7: 0.5 H Postdose	0.4 mmHg Standard Deviation 14.04	2.4 mmHg Standard Deviation 11.22
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 7: 1 H Postdose	-0.7 mmHg Standard Deviation 13.83	3.0 mmHg Standard Deviation 11.35
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 7: 2 H Postdose	0.2 mmHg Standard Deviation 15.73	0.8 mmHg Standard Deviation 12.29
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 7: 12 H Postdose	-3.4 mmHg Standard Deviation 11.68	0.5 mmHg Standard Deviation 12.11
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 8: Predose	-0.8 mmHg Standard Deviation 13.53	2.3 mmHg Standard Deviation 12.96
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 8: 1 H Postdose	1.6 mmHg Standard Deviation 12.35	1.6 mmHg Standard Deviation 14.27
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 9: Predose	0.5 mmHg Standard Deviation 14.43	1.7 mmHg Standard Deviation 11.76
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 9: 1 H Postdose	2.8 mmHg Standard Deviation 16.01	-0.1 mmHg Standard Deviation 14.04
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 10: Predose	0.0 mmHg Standard Deviation 14.32	-0.2 mmHg Standard Deviation 12.08
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 10: 1 H Postdose	0.0 mmHg Standard Deviation 16.48	0.2 mmHg Standard Deviation 11.39
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 11: Predose	-2.5 mmHg Standard Deviation 16.30	4.4 mmHg Standard Deviation 13.67
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 11: 1 H Postdose	-3.6 mmHg Standard Deviation 16.84	3.1 mmHg Standard Deviation 13.00
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 12: Predose	-2.2 mmHg Standard Deviation 11.70	1.7 mmHg Standard Deviation 12.05
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 12: 1 H Postdose	0.4 mmHg Standard Deviation 11.64	2.0 mmHg Standard Deviation 12.33
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 13: Predose	-0.2 mmHg Standard Deviation 13.23	1.4 mmHg Standard Deviation 11.04
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 13: 1 H Postdose	2.3 mmHg Standard Deviation 13.27	-0.2 mmHg Standard Deviation 10.27
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 14: Predose	-2.7 mmHg Standard Deviation 14.09	2.4 mmHg Standard Deviation 12.12
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 14: 1 H Postdose	0.1 mmHg Standard Deviation 14.54	2.9 mmHg Standard Deviation 12.28
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Day 15/ET	0.0 mmHg Standard Deviation 14.14	5.8 mmHg Standard Deviation 12.10
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Follow-up Day 21	2.4 mmHg Standard Deviation 13.92	6.2 mmHg Standard Deviation 14.18
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Follow-up Day 28	1.0 mmHg Standard Deviation 13.83	5.5 mmHg Standard Deviation 11.63
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Follow-up Day 35	2.9 mmHg Standard Deviation 15.58	7.8 mmHg Standard Deviation 13.89
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B CFB at Follow-up Day 42	-0.9 mmHg Standard Deviation 15.02	8.3 mmHg Standard Deviation 13.06

SECONDARY outcome

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part B of the study. H = Hour(s). ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B Baseline	76.1 mmHg Standard Deviation 10.10	75.2 mmHg Standard Deviation 7.91
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 1: 0.25 H Postdose	0.8 mmHg Standard Deviation 5.04	1.0 mmHg Standard Deviation 7.26
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 1: 0.5 H Postdose	-0.1 mmHg Standard Deviation 6.38	0.6 mmHg Standard Deviation 7.09
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 1: 1 H Postdose	0.6 mmHg Standard Deviation 6.40	0.3 mmHg Standard Deviation 8.43
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 1: 2 H Postdose	0.8 mmHg Standard Deviation 7.32	-0.2 mmHg Standard Deviation 8.16
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 1: 12 H Postdose	1.7 mmHg Standard Deviation 9.22	0.2 mmHg Standard Deviation 7.98
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 2: Predose	-0.5 mmHg Standard Deviation 8.77	0.3 mmHg Standard Deviation 7.21
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 2: 0.25 H Postdose	1.8 mmHg Standard Deviation 8.23	0.8 mmHg Standard Deviation 9.53
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 2: 0.5 H Postdose	1.6 mmHg Standard Deviation 7.86	0.2 mmHg Standard Deviation 9.30
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 2: 1 H Postdose	2.2 mmHg Standard Deviation 8.74	-0.3 mmHg Standard Deviation 7.97
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 2: 2 H Postdose	0.8 mmHg Standard Deviation 7.88	1.3 mmHg Standard Deviation 10.10
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 2: 12 H Postdose	-0.1 mmHg Standard Deviation 7.15	-0.5 mmHg Standard Deviation 10.11
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 3: Predose	1.7 mmHg Standard Deviation 7.35	0.1 mmHg Standard Deviation 9.03
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 3: 0.25 H Postdose	3.4 mmHg Standard Deviation 8.57	0.6 mmHg Standard Deviation 8.99
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 3: 0.5 H Postdose	3.0 mmHg Standard Deviation 7.96	-0.4 mmHg Standard Deviation 9.78
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 3: 1 H Postdose	1.3 mmHg Standard Deviation 8.29	0.0 mmHg Standard Deviation 10.69
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 3: 2 H Postdose	1.3 mmHg Standard Deviation 7.97	-0.7 mmHg Standard Deviation 10.86
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 3: 12 H Postdose	-0.5 mmHg Standard Deviation 7.14	-1.7 mmHg Standard Deviation 10.42
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 4: Predose	1.9 mmHg Standard Deviation 9.49	1.5 mmHg Standard Deviation 9.23
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 4: 0.25 H Postdose	1.8 mmHg Standard Deviation 9.53	0.3 mmHg Standard Deviation 10.77
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 4: 0.5 H Postdose	0.9 mmHg Standard Deviation 10.07	0.6 mmHg Standard Deviation 10.50
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 4: 1 H Postdose	1.3 mmHg Standard Deviation 9.83	0.4 mmHg Standard Deviation 9.16
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 4: 2 H Postdose	0.3 mmHg Standard Deviation 9.61	0.9 mmHg Standard Deviation 10.25
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 4: 12 H Postdose	-0.1 mmHg Standard Deviation 9.06	-1.3 mmHg Standard Deviation 9.86
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 5: Predose	-1.5 mmHg Standard Deviation 9.88	0.0 mmHg Standard Deviation 8.94
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 5: 0.25 H Postdose	0.8 mmHg Standard Deviation 9.99	0.1 mmHg Standard Deviation 8.78
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 5: 0.5 H Postdose	1.3 mmHg Standard Deviation 9.75	0.7 mmHg Standard Deviation 9.12
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 5: 1 H Postdose	0.3 mmHg Standard Deviation 9.49	0.3 mmHg Standard Deviation 9.45
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 5: 2 H Postdose	0.8 mmHg Standard Deviation 10.59	-1.3 mmHg Standard Deviation 9.92
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 5: 12 H Postdose	0.0 mmHg Standard Deviation 9.72	-1.3 mmHg Standard Deviation 8.16
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 6: Predose	1.4 mmHg Standard Deviation 10.96	2.1 mmHg Standard Deviation 9.04
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 6: 0.25 H Postdose	0.6 mmHg Standard Deviation 10.12	2.7 mmHg Standard Deviation 7.23
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 6: 0.5 H Postdose	1.3 mmHg Standard Deviation 11.29	2.0 mmHg Standard Deviation 8.85
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 6: 1 H Postdose	1.5 mmHg Standard Deviation 9.74	0.9 mmHg Standard Deviation 10.62
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 6: 2 H Postdose	2.9 mmHg Standard Deviation 11.43	2.7 mmHg Standard Deviation 11.00
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 6: 12 H Postdose	-1.0 mmHg Standard Deviation 8.30	0.4 mmHg Standard Deviation 10.66
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 7: Predose	0.0 mmHg Standard Deviation 8.25	0.5 mmHg Standard Deviation 8.78
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 7: 0.25 H Postdose	1.4 mmHg Standard Deviation 10.33	1.5 mmHg Standard Deviation 9.49
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 7: 0.5 H Postdose	0.2 mmHg Standard Deviation 10.10	2.3 mmHg Standard Deviation 9.66
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 7: 1 H Postdose	0.1 mmHg Standard Deviation 9.03	2.0 mmHg Standard Deviation 9.14
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 7: 2 H Postdose	1.3 mmHg Standard Deviation 11.20	2.1 mmHg Standard Deviation 9.90
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 7: 12 H Postdose	-0.4 mmHg Standard Deviation 8.09	2.0 mmHg Standard Deviation 10.00
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 8: Predose	-0.1 mmHg Standard Deviation 9.22	0.6 mmHg Standard Deviation 7.76
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 8: 1 H Postdose	0.9 mmHg Standard Deviation 9.85	1.9 mmHg Standard Deviation 9.92
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 9: Predose	-0.1 mmHg Standard Deviation 9.03	1.0 mmHg Standard Deviation 8.18
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 9: 1 H Postdose	0.4 mmHg Standard Deviation 9.87	-0.5 mmHg Standard Deviation 10.18
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 10: Predose	-0.5 mmHg Standard Deviation 10.94	0.7 mmHg Standard Deviation 10.23
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 10: 1 H Postdose	0.8 mmHg Standard Deviation 9.97	-0.5 mmHg Standard Deviation 9.14
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 11: Predose	-0.5 mmHg Standard Deviation 11.53	0.6 mmHg Standard Deviation 8.57
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 11: 1 H Postdose	-2.1 mmHg Standard Deviation 10.72	2.2 mmHg Standard Deviation 9.15
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 12: Predose	-1.0 mmHg Standard Deviation 8.94	1.1 mmHg Standard Deviation 7.98
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 12: 1 H Postdose	-0.5 mmHg Standard Deviation 9.17	0.0 mmHg Standard Deviation 9.06
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 13: Predose	0.7 mmHg Standard Deviation 11.64	0.5 mmHg Standard Deviation 9.33
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 13: 1 H Postdose	2.7 mmHg Standard Deviation 10.42	-0.1 mmHg Standard Deviation 8.04
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 14: Predose	-3.3 mmHg Standard Deviation 9.52	1.6 mmHg Standard Deviation 9.68
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 14: 1 H Postdose	1.3 mmHg Standard Deviation 9.96	2.1 mmHg Standard Deviation 8.38
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Day 15/ET	2.4 mmHg Standard Deviation 10.00	4.1 mmHg Standard Deviation 8.94
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Follow-up Day 21	2.8 mmHg Standard Deviation 9.47	3.9 mmHg Standard Deviation 9.13
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Follow-up Day 28	2.9 mmHg Standard Deviation 9.73	3.4 mmHg Standard Deviation 8.42
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Follow-up Day 35	-0.4 mmHg Standard Deviation 11.31	4.3 mmHg Standard Deviation 9.86
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B CFB at Follow-up Day 42	0.5 mmHg Standard Deviation 10.98	4.6 mmHg Standard Deviation 10.46

SECONDARY outcome

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part B of the study. H = Hour(s). ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B Baseline	125.9 mmHg Standard Deviation 14.19	125.1 mmHg Standard Deviation 14.00
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 1: 0.25 H Postdose	0.3 mmHg Standard Deviation 8.48	0.8 mmHg Standard Deviation 8.20
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 1: 0.5 H Postdose	-0.7 mmHg Standard Deviation 8.88	-1.7 mmHg Standard Deviation 12.05
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 1: 1 H Postdose	-0.7 mmHg Standard Deviation 9.44	-0.3 mmHg Standard Deviation 12.46
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 1: 2 H Postdose	0.2 mmHg Standard Deviation 11.68	-2.6 mmHg Standard Deviation 10.56
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 1: 12 H Postdose	-3.8 mmHg Standard Deviation 13.79	-4.5 mmHg Standard Deviation 11.27
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 2: Predose	-1.3 mmHg Standard Deviation 9.20	-0.3 mmHg Standard Deviation 14.50
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 2: 0.25 H Postdose	1.1 mmHg Standard Deviation 10.10	-3.9 mmHg Standard Deviation 15.98
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 2: 0.5 H Postdose	-0.2 mmHg Standard Deviation 10.16	0.4 mmHg Standard Deviation 11.25
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 2: 1 H Postdose	-0.7 mmHg Standard Deviation 11.01	-1.8 mmHg Standard Deviation 10.26
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 2: 2 H Postdose	-1.5 mmHg Standard Deviation 11.38	-2.7 mmHg Standard Deviation 12.51
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 2: 12 H Postdose	-5.5 mmHg Standard Deviation 11.62	-2.4 mmHg Standard Deviation 12.67
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 3: Predose	-3.0 mmHg Standard Deviation 10.48	0.1 mmHg Standard Deviation 13.03
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 3: 0.25 H Postdose	-0.1 mmHg Standard Deviation 11.97	-0.2 mmHg Standard Deviation 12.78
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 3: 0.5 H Postdose	-1.0 mmHg Standard Deviation 12.26	-2.1 mmHg Standard Deviation 10.83
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 3: 1 H Postdose	-0.7 mmHg Standard Deviation 12.22	-1.7 mmHg Standard Deviation 13.34
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 3: 2 H Postdose	-1.9 mmHg Standard Deviation 11.45	-1.4 mmHg Standard Deviation 14.55
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 3: 12 H Postdose	-4.3 mmHg Standard Deviation 8.94	-3.4 mmHg Standard Deviation 11.42
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 4: Predose	-1.2 mmHg Standard Deviation 16.11	-0.2 mmHg Standard Deviation 10.91
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 4: 0.25 H Postdose	-1.3 mmHg Standard Deviation 13.21	1.6 mmHg Standard Deviation 11.83
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 4: 0.5 H Postdose	-1.9 mmHg Standard Deviation 10.60	-0.4 mmHg Standard Deviation 9.38
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 4: 1 H Postdose	-3.1 mmHg Standard Deviation 13.79	1.2 mmHg Standard Deviation 10.70
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 4: 2 H Postdose	-2.5 mmHg Standard Deviation 13.34	-1.8 mmHg Standard Deviation 13.77
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 4: 12 H Postdose	-5.5 mmHg Standard Deviation 13.01	-4.5 mmHg Standard Deviation 11.79
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 5: Predose	-1.3 mmHg Standard Deviation 12.57	1.3 mmHg Standard Deviation 13.70
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 5: 0.25 H Postdose	-0.5 mmHg Standard Deviation 11.86	1.4 mmHg Standard Deviation 13.22
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 5: 0.5 H Postdose	-1.0 mmHg Standard Deviation 11.04	1.3 mmHg Standard Deviation 11.90
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 5: 1 H Postdose	-2.4 mmHg Standard Deviation 10.89	1.8 mmHg Standard Deviation 11.63
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 5: 2 H Postdose	-1.6 mmHg Standard Deviation 13.12	-2.2 mmHg Standard Deviation 12.56
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 5: 12 H Postdose	-5.5 mmHg Standard Deviation 14.11	-3.5 mmHg Standard Deviation 13.36
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 6: Predose	-4.2 mmHg Standard Deviation 14.69	3.2 mmHg Standard Deviation 13.50
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 6: 0.25 H Postdose	-1.6 mmHg Standard Deviation 11.52	2.8 mmHg Standard Deviation 12.65
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 6: 0.5 H Postdose	-3.6 mmHg Standard Deviation 12.23	1.7 mmHg Standard Deviation 14.73
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 6: 1 H Postdose	-1.9 mmHg Standard Deviation 12.98	2.3 mmHg Standard Deviation 14.61
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 6: 2 H Postdose	-2.9 mmHg Standard Deviation 12.89	2.2 mmHg Standard Deviation 13.98
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 6: 12 H Postdose	-5.7 mmHg Standard Deviation 11.59	-1.6 mmHg Standard Deviation 13.21
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 7: Predose	-2.8 mmHg Standard Deviation 14.48	4.3 mmHg Standard Deviation 15.71
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 7: 0.25 H Postdose	-2.6 mmHg Standard Deviation 15.62	1.2 mmHg Standard Deviation 13.56
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 7: 0.5 H Postdose	-2.6 mmHg Standard Deviation 15.42	1.0 mmHg Standard Deviation 11.22
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 7: 1 H Postdose	-1.5 mmHg Standard Deviation 15.18	1.5 mmHg Standard Deviation 12.20
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 7: 2 H Postdose	-2.9 mmHg Standard Deviation 16.37	-1.9 mmHg Standard Deviation 10.48
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 7: 12 H Postdose	-6.9 mmHg Standard Deviation 12.84	-3.2 mmHg Standard Deviation 11.19
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 8: Predose	-2.2 mmHg Standard Deviation 13.37	1.9 mmHg Standard Deviation 10.57
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 8: 1 H Postdose	-0.9 mmHg Standard Deviation 10.82	0.6 mmHg Standard Deviation 11.49
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 9: Predose	-3.9 mmHg Standard Deviation 13.94	1.5 mmHg Standard Deviation 13.77
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 9: 1 H Postdose	-2.6 mmHg Standard Deviation 14.50	0.8 mmHg Standard Deviation 11.08
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 10: Predose	-2.1 mmHg Standard Deviation 16.07	-0.7 mmHg Standard Deviation 11.64
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 10: 1 H Postdose	-1.2 mmHg Standard Deviation 16.73	-0.6 mmHg Standard Deviation 16.41
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 11: Predose	-4.8 mmHg Standard Deviation 16.81	2.0 mmHg Standard Deviation 17.24
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 11: 1 H Postdose	-6.1 mmHg Standard Deviation 16.18	-0.1 mmHg Standard Deviation 12.09
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 12: Predose	-2.3 mmHg Standard Deviation 13.70	2.4 mmHg Standard Deviation 12.20
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 12: 1 H Postdose	-2.5 mmHg Standard Deviation 13.80	3.1 mmHg Standard Deviation 14.10
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 13: Predose	-4.1 mmHg Standard Deviation 12.65	0.6 mmHg Standard Deviation 11.69
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 13: 1 H Postdose	-1.6 mmHg Standard Deviation 10.92	1.8 mmHg Standard Deviation 11.83
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 14: Predose	-4.4 mmHg Standard Deviation 12.31	2.3 mmHg Standard Deviation 11.60
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 14: 1 H Postdose	-1.2 mmHg Standard Deviation 13.75	3.1 mmHg Standard Deviation 13.90
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Day 15/ET	-2.8 mmHg Standard Deviation 13.56	-0.3 mmHg Standard Deviation 11.32
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Follow-up Day 21	-1.7 mmHg Standard Deviation 14.21	1.7 mmHg Standard Deviation 12.63
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Follow-up Day 28	-3.2 mmHg Standard Deviation 12.13	-1.9 mmHg Standard Deviation 11.32
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Follow-up Day 35	-1.0 mmHg Standard Deviation 13.00	2.6 mmHg Standard Deviation 12.04
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B CFB at Follow-up Day 42	-2.5 mmHg Standard Deviation 14.02	0.8 mmHg Standard Deviation 9.94

SECONDARY outcome

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part B of the study. H = Hour(s). ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B Baseline	81.9 mmHg Standard Deviation 9.32	80.1 mmHg Standard Deviation 8.26
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 1: 0.25 H Postdose	1.0 mmHg Standard Deviation 7.45	2.6 mmHg Standard Deviation 6.06
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 1: 0.5 H Postdose	0.7 mmHg Standard Deviation 7.24	1.5 mmHg Standard Deviation 7.30
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 1: 1 H Postdose	-0.7 mmHg Standard Deviation 7.75	0.8 mmHg Standard Deviation 9.09
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 1: 2 H Postdose	1.5 mmHg Standard Deviation 7.41	0.4 mmHg Standard Deviation 8.13
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 1: 12 H Postdose	-0.1 mmHg Standard Deviation 9.77	0.0 mmHg Standard Deviation 7.96
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 2: Predose	-1.5 mmHg Standard Deviation 8.02	0.9 mmHg Standard Deviation 8.07
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 2: 0.25 H Postdose	1.7 mmHg Standard Deviation 6.86	-1.2 mmHg Standard Deviation 11.02
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 2: 0.5 H Postdose	-0.2 mmHg Standard Deviation 7.06	0.1 mmHg Standard Deviation 8.21
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 2: 1 H Postdose	0.8 mmHg Standard Deviation 6.27	-1.8 mmHg Standard Deviation 8.47
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 2: 2 H Postdose	0.0 mmHg Standard Deviation 7.65	0.6 mmHg Standard Deviation 8.05
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 2: 12 H Postdose	-0.1 mmHg Standard Deviation 7.87	1.1 mmHg Standard Deviation 9.87
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 3: Predose	-1.5 mmHg Standard Deviation 7.83	-0.4 mmHg Standard Deviation 8.08
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 3: 0.25 H Postdose	1.0 mmHg Standard Deviation 8.05	0.4 mmHg Standard Deviation 8.02
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 3: 0.5 H Postdose	1.3 mmHg Standard Deviation 8.28	-0.4 mmHg Standard Deviation 8.11
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 3: 1 H Postdose	0.3 mmHg Standard Deviation 8.17	-0.7 mmHg Standard Deviation 9.97
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 3: 2 H Postdose	-0.4 mmHg Standard Deviation 8.57	-0.1 mmHg Standard Deviation 10.06
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 3: 12 H Postdose	-0.5 mmHg Standard Deviation 6.72	-0.4 mmHg Standard Deviation 8.59
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 4: Predose	-0.7 mmHg Standard Deviation 9.70	2.4 mmHg Standard Deviation 9.41
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 4: 0.25 H Postdose	0.1 mmHg Standard Deviation 9.23	2.2 mmHg Standard Deviation 9.94
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 4: 0.5 H Postdose	0.3 mmHg Standard Deviation 8.49	0.2 mmHg Standard Deviation 9.36
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 4: 1 H Postdose	0.2 mmHg Standard Deviation 8.06	0.3 mmHg Standard Deviation 10.05
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 4: 2 H Postdose	0.6 mmHg Standard Deviation 9.46	-0.8 mmHg Standard Deviation 10.84
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 4: 12 H Postdose	0.0 mmHg Standard Deviation 8.35	-0.6 mmHg Standard Deviation 9.38
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 5: Predose	-1.1 mmHg Standard Deviation 8.74	-0.2 mmHg Standard Deviation 8.65
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 5: 0.25 H Postdose	0.2 mmHg Standard Deviation 8.12	0.6 mmHg Standard Deviation 9.08
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 5: 0.5 H Postdose	-1.1 mmHg Standard Deviation 10.02	0.8 mmHg Standard Deviation 9.19
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 5: 1 H Postdose	-0.7 mmHg Standard Deviation 8.56	1.3 mmHg Standard Deviation 10.24
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 5: 2 H Postdose	-1.3 mmHg Standard Deviation 9.05	-0.5 mmHg Standard Deviation 9.62
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 5: 12 H Postdose	-2.1 mmHg Standard Deviation 8.54	-0.3 mmHg Standard Deviation 11.77
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 6: Predose	-0.9 mmHg Standard Deviation 9.09	1.8 mmHg Standard Deviation 11.79
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 6: 0.25 H Postdose	-0.6 mmHg Standard Deviation 10.69	3.0 mmHg Standard Deviation 8.78
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 6: 0.5 H Postdose	0.0 mmHg Standard Deviation 10.09	1.3 mmHg Standard Deviation 12.70
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 6: 1 H Postdose	1.2 mmHg Standard Deviation 9.07	2.3 mmHg Standard Deviation 11.84
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 6: 2 H Postdose	1.0 mmHg Standard Deviation 9.85	1.7 mmHg Standard Deviation 9.93
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 6: 12 H Postdose	-0.7 mmHg Standard Deviation 7.21	1.6 mmHg Standard Deviation 12.66
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 7: Predose	-0.6 mmHg Standard Deviation 9.33	-0.5 mmHg Standard Deviation 8.27
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 7: 0.25 H Postdose	2.3 mmHg Standard Deviation 8.89	0.2 mmHg Standard Deviation 9.03
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 7: 0.5 H Postdose	0.1 mmHg Standard Deviation 11.03	0.7 mmHg Standard Deviation 11.28
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 7: 1 H Postdose	0.8 mmHg Standard Deviation 10.89	0.8 mmHg Standard Deviation 10.27
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 7: 2 H Postdose	-0.2 mmHg Standard Deviation 9.69	0.6 mmHg Standard Deviation 8.90
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 7: 12 H Postdose	-2.7 mmHg Standard Deviation 7.17	0.4 mmHg Standard Deviation 9.28
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 8: Predose	-0.3 mmHg Standard Deviation 9.52	0.7 mmHg Standard Deviation 9.77
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 8: 1 H Postdose	-0.4 mmHg Standard Deviation 7.18	2.3 mmHg Standard Deviation 8.57
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 9: Predose	-1.5 mmHg Standard Deviation 9.64	0.5 mmHg Standard Deviation 7.27
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 9: 1 H Postdose	0.6 mmHg Standard Deviation 9.66	1.7 mmHg Standard Deviation 8.83
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 10: Predose	0.2 mmHg Standard Deviation 8.57	2.0 mmHg Standard Deviation 10.21
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 10: 1 H Postdose	0.0 mmHg Standard Deviation 10.47	1.7 mmHg Standard Deviation 12.59
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 11: Predose	-2.3 mmHg Standard Deviation 12.73	1.6 mmHg Standard Deviation 13.81
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 11: 1 H Postdose	-4.3 mmHg Standard Deviation 12.66	0.0 mmHg Standard Deviation 10.73
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 12: Predose	2.1 mmHg Standard Deviation 9.35	1.2 mmHg Standard Deviation 10.41
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 12: 1 H Postdose	-1.4 mmHg Standard Deviation 11.63	2.0 mmHg Standard Deviation 12.93
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 13: Predose	0.0 mmHg Standard Deviation 9.92	2.1 mmHg Standard Deviation 8.87
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 13: 1 H Postdose	0.7 mmHg Standard Deviation 7.60	-0.8 mmHg Standard Deviation 9.39
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 14: Predose	-2.8 mmHg Standard Deviation 9.26	2.5 mmHg Standard Deviation 9.59
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 14: 1 H Postdose	1.2 mmHg Standard Deviation 10.72	1.8 mmHg Standard Deviation 8.36
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Day 15/ET	0.8 mmHg Standard Deviation 9.09	1.5 mmHg Standard Deviation 8.41
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Follow-up Day 21	1.7 mmHg Standard Deviation 8.65	2.3 mmHg Standard Deviation 8.58
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Follow-up Day 28	-0.3 mmHg Standard Deviation 7.05	1.9 mmHg Standard Deviation 9.00
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Follow-up Day 35	-0.4 mmHg Standard Deviation 8.34	3.5 mmHg Standard Deviation 9.60
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B CFB at Follow-up Day 42	0.3 mmHg Standard Deviation 9.61	2.5 mmHg Standard Deviation 7.69

SECONDARY outcome

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part B of the study. H = Hour(s). ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Heart Rate - Part B Baseline	74.3 beats/min Standard Deviation 12.80	76.8 beats/min Standard Deviation 12.33
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 1: 0.25 H Postdose	-1.9 beats/min Standard Deviation 9.96	-2.8 beats/min Standard Deviation 8.50
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 1: 0.5 H Postdose	-2.1 beats/min Standard Deviation 10.77	-2.5 beats/min Standard Deviation 9.26
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 1: 1 H Postdose	-1.8 beats/min Standard Deviation 11.14	-4.6 beats/min Standard Deviation 9.13
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 1: 2 H Postdose	-0.8 beats/min Standard Deviation 12.63	-1.1 beats/min Standard Deviation 9.30
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 1: 12 H Postdose	-1.0 beats/min Standard Deviation 11.53	-4.3 beats/min Standard Deviation 12.18
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 2: Predose	2.5 beats/min Standard Deviation 11.80	-1.8 beats/min Standard Deviation 11.47
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 2: 0.25 H Postdose	-0.2 beats/min Standard Deviation 10.75	-1.8 beats/min Standard Deviation 11.79
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 2: 0.5 H Postdose	-1.0 beats/min Standard Deviation 10.98	-2.4 beats/min Standard Deviation 10.50
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 2: 1 H Postdose	-0.2 beats/min Standard Deviation 11.79	-3.0 beats/min Standard Deviation 11.15
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 2: 2 H Postdose	-1.7 beats/min Standard Deviation 8.50	-1.3 beats/min Standard Deviation 11.50
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 2: 12 H Postdose	-2.3 beats/min Standard Deviation 11.09	-4.0 beats/min Standard Deviation 11.51
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 3: Predose	2.5 beats/min Standard Deviation 12.40	-0.7 beats/min Standard Deviation 13.35
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 3: 0.25 H Postdose	0.0 beats/min Standard Deviation 9.56	-1.4 beats/min Standard Deviation 10.93
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 3: 0.5 H Postdose	-0.5 beats/min Standard Deviation 10.82	-1.8 beats/min Standard Deviation 11.57
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 3: 1 H Postdose	0.8 beats/min Standard Deviation 10.24	-1.2 beats/min Standard Deviation 11.03
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 3: 2 H Postdose	0.4 beats/min Standard Deviation 12.45	-0.5 beats/min Standard Deviation 11.19
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 3: 12 H Postdose	-3.0 beats/min Standard Deviation 10.46	-4.2 beats/min Standard Deviation 11.62
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 4: Predose	4.9 beats/min Standard Deviation 10.28	2.0 beats/min Standard Deviation 10.30
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 4: 0.25 H Postdose	2.8 beats/min Standard Deviation 9.06	3.5 beats/min Standard Deviation 15.13
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 4: 0.5 H Postdose	1.9 beats/min Standard Deviation 10.43	-1.4 beats/min Standard Deviation 10.73
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 4: 1 H Postdose	1.4 beats/min Standard Deviation 9.75	-0.8 beats/min Standard Deviation 10.63
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 4: 2 H Postdose	1.1 beats/min Standard Deviation 11.94	1.6 beats/min Standard Deviation 12.66
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 4: 12 H Postdose	-0.6 beats/min Standard Deviation 11.36	-3.6 beats/min Standard Deviation 11.76
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 5: Predose	4.3 beats/min Standard Deviation 11.14	1.9 beats/min Standard Deviation 9.70
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 5: 0.25 H Postdose	2.4 beats/min Standard Deviation 11.59	0.3 beats/min Standard Deviation 12.44
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 5: 0.5 H Postdose	3.7 beats/min Standard Deviation 11.81	0.0 beats/min Standard Deviation 9.57
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 5: 1 H Postdose	0.6 beats/min Standard Deviation 10.52	2.0 beats/min Standard Deviation 12.34
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 5: 2 H Postdose	1.5 beats/min Standard Deviation 11.68	2.5 beats/min Standard Deviation 10.62
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 5: 12 H Postdose	-0.2 beats/min Standard Deviation 14.80	-1.4 beats/min Standard Deviation 12.45
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 6: Predose	4.7 beats/min Standard Deviation 10.64	3.9 beats/min Standard Deviation 8.00
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 6: 0.25 H Postdose	3.1 beats/min Standard Deviation 11.30	0.7 beats/min Standard Deviation 9.81
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 6: 0.5 H Postdose	2.5 beats/min Standard Deviation 11.80	0.4 beats/min Standard Deviation 10.44
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 6: 1 H Postdose	3.2 beats/min Standard Deviation 12.71	0.4 beats/min Standard Deviation 8.54
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 6: 2 H Postdose	2.6 beats/min Standard Deviation 9.70	0.5 beats/min Standard Deviation 11.53
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 6: 12 H Postdose	1.4 beats/min Standard Deviation 12.65	-2.3 beats/min Standard Deviation 12.57
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 7: Predose	3.7 beats/min Standard Deviation 10.26	3.0 beats/min Standard Deviation 11.63
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 7: 0.25 H Postdose	3.9 beats/min Standard Deviation 12.00	1.5 beats/min Standard Deviation 11.16
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 7: 0.5 H Postdose	3.7 beats/min Standard Deviation 12.25	-0.4 beats/min Standard Deviation 11.19
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 7: 1 H Postdose	5.5 beats/min Standard Deviation 13.30	1.4 beats/min Standard Deviation 11.25
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 7: 2 H Postdose	0.9 beats/min Standard Deviation 10.64	2.2 beats/min Standard Deviation 13.04
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 7: 12 H Postdose	-0.4 beats/min Standard Deviation 11.53	-1.3 beats/min Standard Deviation 13.75
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 8: Predose	10.1 beats/min Standard Deviation 14.90	6.9 beats/min Standard Deviation 14.46
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 8: 1 H Postdose	8.5 beats/min Standard Deviation 12.78	6.9 beats/min Standard Deviation 12.02
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 9: Predose	7.7 beats/min Standard Deviation 10.64	7.5 beats/min Standard Deviation 12.00
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 9: 1 H Postdose	5.9 beats/min Standard Deviation 10.94	4.4 beats/min Standard Deviation 12.05
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 10: Predose	6.4 beats/min Standard Deviation 11.40	8.9 beats/min Standard Deviation 13.59
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 10: 1 H Postdose	4.0 beats/min Standard Deviation 12.11	6.1 beats/min Standard Deviation 13.09
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 11: Predose	6.2 beats/min Standard Deviation 15.10	4.6 beats/min Standard Deviation 11.26
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 11: 1 H Postdose	4.3 beats/min Standard Deviation 14.76	4.5 beats/min Standard Deviation 11.22
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 12: Predose	4.4 beats/min Standard Deviation 11.99	3.8 beats/min Standard Deviation 13.85
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 12: 1 H Postdose	4.8 beats/min Standard Deviation 13.56	2.1 beats/min Standard Deviation 13.19
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 13: Predose	3.1 beats/min Standard Deviation 12.72	4.1 beats/min Standard Deviation 11.22
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 13: 1 H Postdose	2.9 beats/min Standard Deviation 10.46	5.0 beats/min Standard Deviation 11.53
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 14: Predose	6.4 beats/min Standard Deviation 12.18	4.6 beats/min Standard Deviation 10.91
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 14: 1 H Postdose	3.6 beats/min Standard Deviation 10.21	2.8 beats/min Standard Deviation 9.96
Change From Baseline (CFB) in Heart Rate - Part B CFB at Day 15/ET	-1.6 beats/min Standard Deviation 12.73	-0.1 beats/min Standard Deviation 10.78
Change From Baseline (CFB) in Heart Rate - Part B CFB at Follow-up Day 21	0.1 beats/min Standard Deviation 10.32	-5.9 beats/min Standard Deviation 10.54
Change From Baseline (CFB) in Heart Rate - Part B CFB at Follow-up Day 28	-0.5 beats/min Standard Deviation 13.06	-5.3 beats/min Standard Deviation 15.54
Change From Baseline (CFB) in Heart Rate - Part B CFB at Follow-up Day 35	-3.8 beats/min Standard Deviation 11.13	-3.9 beats/min Standard Deviation 13.47
Change From Baseline (CFB) in Heart Rate - Part B CFB at Follow-up Day 42	-3.7 beats/min Standard Deviation 11.93	-6.0 beats/min Standard Deviation 12.73

SECONDARY outcome

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part B of the study. H = Hour(s). ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 5: 0.25 H Postdose	0.0 breaths/min Standard Deviation 2.10	0.1 breaths/min Standard Deviation 1.87
Change From Baseline (CFB) in Respiratory Rate - Part B Baseline	16.7 breaths/min Standard Deviation 1.72	16.8 breaths/min Standard Deviation 1.41
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 1: 0.25 H Postdose	0.2 breaths/min Standard Deviation 1.24	-0.1 breaths/min Standard Deviation 1.05
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 1: 0.5 H Postdose	0.4 breaths/min Standard Deviation 1.08	0.0 breaths/min Standard Deviation 0.71
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 1: 1 H Postdose	0.3 breaths/min Standard Deviation 1.76	0.1 breaths/min Standard Deviation 1.00
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 1: 2 H Postdose	0.4 breaths/min Standard Deviation 1.66	-0.1 breaths/min Standard Deviation 0.98
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 1: 12 H Postdose	-0.3 breaths/min Standard Deviation 1.99	0.2 breaths/min Standard Deviation 1.65
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 2: Predose	-0.1 breaths/min Standard Deviation 2.36	0.0 breaths/min Standard Deviation 1.48
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 2: 0.25 H Postdose	0.0 breaths/min Standard Deviation 1.86	0.0 breaths/min Standard Deviation 1.41
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 2: 0.5 H Postdose	0.4 breaths/min Standard Deviation 1.94	0.1 breaths/min Standard Deviation 1.59
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 2: 1 H Postdose	0.1 breaths/min Standard Deviation 1.89	-0.2 breaths/min Standard Deviation 1.40
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 2: 2 H Postdose	0.3 breaths/min Standard Deviation 1.88	0.0 breaths/min Standard Deviation 1.45
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 2: 12 H Postdose	-0.2 breaths/min Standard Deviation 2.14	0.0 breaths/min Standard Deviation 1.83
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 3: Predose	0.0 breaths/min Standard Deviation 1.88	0.1 breaths/min Standard Deviation 2.07
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 3: 0.25 H Postdose	0.0 breaths/min Standard Deviation 1.87	0.0 breaths/min Standard Deviation 1.52
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 3: 0.5 H Postdose	0.0 breaths/min Standard Deviation 2.00	0.0 breaths/min Standard Deviation 1.45
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 3: 1 H Postdose	0.2 breaths/min Standard Deviation 2.14	0.2 breaths/min Standard Deviation 1.51
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 3: 2 H Postdose	0.4 breaths/min Standard Deviation 1.94	0.3 breaths/min Standard Deviation 1.63
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 3: 12 H Postdose	0.0 breaths/min Standard Deviation 2.33	0.2 breaths/min Standard Deviation 1.82
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 4: Predose	0.3 breaths/min Standard Deviation 1.92	-0.1 breaths/min Standard Deviation 1.75
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 4: 0.25 H Postdose	0.4 breaths/min Standard Deviation 1.94	-0.1 breaths/min Standard Deviation 2.03
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 4: 0.5 H Postdose	0.2 breaths/min Standard Deviation 2.12	0.2 breaths/min Standard Deviation 1.90
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 4: 1 H Postdose	0.3 breaths/min Standard Deviation 1.71	0.4 breaths/min Standard Deviation 2.01
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 4: 2 H Postdose	0.2 breaths/min Standard Deviation 1.80	0.1 breaths/min Standard Deviation 1.90
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 4: 12 H Postdose	0.2 breaths/min Standard Deviation 2.46	0.2 breaths/min Standard Deviation 2.43
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 5: Predose	0.3 breaths/min Standard Deviation 2.23	0.0 breaths/min Standard Deviation 1.82
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 5: 0.5 H Postdose	0.1 breaths/min Standard Deviation 2.10	0.0 breaths/min Standard Deviation 1.82
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 5: 1 H Postdose	0.2 breaths/min Standard Deviation 2.16	0.2 breaths/min Standard Deviation 1.66
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 5: 2 H Postdose	0.2 breaths/min Standard Deviation 2.13	0.1 breaths/min Standard Deviation 1.90
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 5: 12 H Postdose	0.1 breaths/min Standard Deviation 2.24	0.4 breaths/min Standard Deviation 2.01
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 6: Predose	0.5 breaths/min Standard Deviation 2.02	0.6 breaths/min Standard Deviation 2.56
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 6: 0.25 H Postdose	0.6 breaths/min Standard Deviation 2.11	0.2 breaths/min Standard Deviation 1.85
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 6: 0.5 H Postdose	0.3 breaths/min Standard Deviation 1.95	0.2 breaths/min Standard Deviation 1.81
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 6: 1 H Postdose	0.3 breaths/min Standard Deviation 1.71	0.2 breaths/min Standard Deviation 2.00
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 6: 2 H Postdose	0.5 breaths/min Standard Deviation 2.18	0.4 breaths/min Standard Deviation 1.84
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 6: 12 H Postdose	0.1 breaths/min Standard Deviation 1.92	1.4 breaths/min Standard Deviation 8.64
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 7: Predose	0.8 breaths/min Standard Deviation 2.70	0.7 breaths/min Standard Deviation 1.91
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 7: 0.25 H Postdose	1.0 breaths/min Standard Deviation 2.71	0.0 breaths/min Standard Deviation 2.01
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 7: 0.5 H Postdose	1.1 breaths/min Standard Deviation 2.28	0.3 breaths/min Standard Deviation 1.48
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 7: 1 H Postdose	0.8 breaths/min Standard Deviation 2.48	0.4 breaths/min Standard Deviation 1.99
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 7: 2 H Postdose	0.5 breaths/min Standard Deviation 2.26	0.5 breaths/min Standard Deviation 1.91
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 7: 12 H Postdose	-0.2 breaths/min Standard Deviation 1.96	0.1 breaths/min Standard Deviation 1.73
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 8: Predose	0.5 breaths/min Standard Deviation 2.05	0.4 breaths/min Standard Deviation 1.88
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 8: 1 H Postdose	1.0 breaths/min Standard Deviation 2.26	0.4 breaths/min Standard Deviation 1.65
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 9: Predose	0.7 breaths/min Standard Deviation 2.22	0.3 breaths/min Standard Deviation 1.81
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 9: 1 H Postdose	0.4 breaths/min Standard Deviation 1.91	0.1 breaths/min Standard Deviation 1.82
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 10: Predose	0.5 breaths/min Standard Deviation 1.60	0.5 breaths/min Standard Deviation 2.05
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 10: 1 H Postdose	0.5 breaths/min Standard Deviation 2.21	0.6 breaths/min Standard Deviation 1.67
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 11: Predose	0.3 breaths/min Standard Deviation 1.97	0.5 breaths/min Standard Deviation 1.99
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 11: 1 H Postdose	0.3 breaths/min Standard Deviation 2.18	0.3 breaths/min Standard Deviation 2.04
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 12: Predose	0.7 breaths/min Standard Deviation 2.27	0.5 breaths/min Standard Deviation 1.93
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 12: 1 H Postdose	0.6 breaths/min Standard Deviation 2.05	0.4 breaths/min Standard Deviation 1.83
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 13: Predose	1.0 breaths/min Standard Deviation 1.94	0.4 breaths/min Standard Deviation 1.96
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 13: 1 H Postdose	1.0 breaths/min Standard Deviation 2.18	0.3 breaths/min Standard Deviation 1.79
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 14: Predose	0.8 breaths/min Standard Deviation 2.08	0.1 breaths/min Standard Deviation 2.89
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 14: 1 H Postdose	0.9 breaths/min Standard Deviation 1.98	0.4 breaths/min Standard Deviation 1.61
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Day 15/ET	1.2 breaths/min Standard Deviation 8.39	-0.4 breaths/min Standard Deviation 1.59
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Follow-up Day 21	0.1 breaths/min Standard Deviation 2.21	0.2 breaths/min Standard Deviation 1.70
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Follow-up Day 28	0.0 breaths/min Standard Deviation 2.15	0.0 breaths/min Standard Deviation 1.88
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Follow-up Day 35	0.0 breaths/min Standard Deviation 2.40	0.1 breaths/min Standard Deviation 1.64
Change From Baseline (CFB) in Respiratory Rate - Part B CFB at Follow-up Day 42	-0.2 breaths/min Standard Deviation 2.48	0.1 breaths/min Standard Deviation 1.50

SECONDARY outcome

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part B of the study. H = Hour(s). ET = Early Termination.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 12: Predose	0.01 degrees C Standard Deviation 0.422	-0.06 degrees C Standard Deviation 0.358
Change From Baseline (CFB) in Oral Temperature - Part B Baseline	36.72 degrees C Standard Deviation 0.298	36.72 degrees C Standard Deviation 0.324
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 1: 0.25 H Postdose	0.03 degrees C Standard Deviation 0.309	0.03 degrees C Standard Deviation 0.374
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 1: 0.5 H Postdose	0.03 degrees C Standard Deviation 0.315	0.05 degrees C Standard Deviation 0.367
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 1: 1 H Postdose	0.05 degrees C Standard Deviation 0.311	-0.02 degrees C Standard Deviation 0.414
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 1: 2 H Postdose	0.03 degrees C Standard Deviation 0.360	-0.05 degrees C Standard Deviation 0.384
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 1: 12 H Postdose	-0.09 degrees C Standard Deviation 0.328	-0.10 degrees C Standard Deviation 0.382
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 2: Predose	-0.04 degrees C Standard Deviation 0.250	-0.01 degrees C Standard Deviation 0.283
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 2: 0.25 H Postdose	-0.03 degrees C Standard Deviation 0.330	-0.04 degrees C Standard Deviation 0.421
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 2: 0.5 H Postdose	0.01 degrees C Standard Deviation 0.284	-0.06 degrees C Standard Deviation 0.539
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 2: 1 H Postdose	-0.05 degrees C Standard Deviation 0.242	-0.02 degrees C Standard Deviation 0.371
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 2: 2 H Postdose	-0.06 degrees C Standard Deviation 0.257	-0.05 degrees C Standard Deviation 0.327
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 2: 12 H Postdose	-0.13 degrees C Standard Deviation 0.307	-0.06 degrees C Standard Deviation 0.397
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 3: Predose	-0.03 degrees C Standard Deviation 0.403	-0.02 degrees C Standard Deviation 0.321
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 3: 0.25 H Postdose	-0.06 degrees C Standard Deviation 0.417	-0.05 degrees C Standard Deviation 0.332
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 3: 0.5 H Postdose	0.08 degrees C Standard Deviation 0.408	-0.03 degrees C Standard Deviation 0.361
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 3: 1 H Postdose	0.03 degrees C Standard Deviation 0.430	-0.04 degrees C Standard Deviation 0.330
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 3: 2 H Postdose	-0.03 degrees C Standard Deviation 0.353	0.00 degrees C Standard Deviation 0.380
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 3: 12 H Postdose	-0.13 degrees C Standard Deviation 0.269	-0.08 degrees C Standard Deviation 0.339
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 4: Predose	-0.14 degrees C Standard Deviation 0.421	-0.03 degrees C Standard Deviation 0.348
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 4: 0.25 H Postdose	-0.07 degrees C Standard Deviation 0.335	-0.04 degrees C Standard Deviation 0.343
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 4: 0.5 H Postdose	-0.03 degrees C Standard Deviation 0.414	-0.04 degrees C Standard Deviation 0.333
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 4: 1 H Postdose	-0.11 degrees C Standard Deviation 0.310	0.01 degrees C Standard Deviation 0.392
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 4: 2 H Postdose	-0.02 degrees C Standard Deviation 0.458	-0.04 degrees C Standard Deviation 0.367
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 4: 12 H Postdose	-0.07 degrees C Standard Deviation 0.370	0.01 degrees C Standard Deviation 0.586
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 5: Predose	0.01 degrees C Standard Deviation 0.414	-0.01 degrees C Standard Deviation 0.343
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 5: 0.25 H Postdose	0.01 degrees C Standard Deviation 0.376	-0.03 degrees C Standard Deviation 0.349
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 5: 0.5 H Postdose	0.07 degrees C Standard Deviation 0.359	-0.08 degrees C Standard Deviation 0.359
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 5: 1 H Postdose	-0.01 degrees C Standard Deviation 0.345	-0.01 degrees C Standard Deviation 0.354
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 5: 2 H Postdose	-0.04 degrees C Standard Deviation 0.301	-0.08 degrees C Standard Deviation 0.349
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 5: 12 H Postdose	-0.09 degrees C Standard Deviation 0.322	-0.12 degrees C Standard Deviation 0.277
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 6: Predose	0.06 degrees C Standard Deviation 0.381	0.07 degrees C Standard Deviation 0.428
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 6: 0.25 H Postdose	0.01 degrees C Standard Deviation 0.381	0.04 degrees C Standard Deviation 0.523
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 6: 0.5 H Postdose	0.04 degrees C Standard Deviation 0.401	0.00 degrees C Standard Deviation 0.376
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 6: 1 H Postdose	0.04 degrees C Standard Deviation 0.373	-0.05 degrees C Standard Deviation 0.392
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 6: 2 H Postdose	0.05 degrees C Standard Deviation 0.405	0.01 degrees C Standard Deviation 0.452
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 6: 12 H Postdose	-0.10 degrees C Standard Deviation 0.341	-0.10 degrees C Standard Deviation 0.366
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 7: Predose	0.02 degrees C Standard Deviation 0.386	0.02 degrees C Standard Deviation 0.430
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 7: 0.25 H Postdose	-0.04 degrees C Standard Deviation 0.341	-0.02 degrees C Standard Deviation 0.358
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 7: 0.5 H Postdose	0.05 degrees C Standard Deviation 0.402	0.00 degrees C Standard Deviation 0.390
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 7: 1 H Postdose	0.05 degrees C Standard Deviation 0.388	0.06 degrees C Standard Deviation 0.444
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 7: 2 H Postdose	0.01 degrees C Standard Deviation 0.489	0.01 degrees C Standard Deviation 0.387
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 7: 12 H Postdose	-0.06 degrees C Standard Deviation 0.350	-0.10 degrees C Standard Deviation 0.353
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 8: Predose	0.05 degrees C Standard Deviation 0.350	0.02 degrees C Standard Deviation 0.388
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 8: 1 H Postdose	0.11 degrees C Standard Deviation 0.372	0.02 degrees C Standard Deviation 0.355
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 9: Predose	0.04 degrees C Standard Deviation 0.421	0.04 degrees C Standard Deviation 0.414
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 9: 1 H Postdose	0.09 degrees C Standard Deviation 0.404	0.05 degrees C Standard Deviation 0.389
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 10: Predose	-0.01 degrees C Standard Deviation 0.409	-0.04 degrees C Standard Deviation 0.402
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 10: 1 H Postdose	0.06 degrees C Standard Deviation 0.454	0.01 degrees C Standard Deviation 0.412
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 11: Predose	-0.02 degrees C Standard Deviation 0.536	-0.06 degrees C Standard Deviation 0.382
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 11: 1 H Postdose	-0.05 degrees C Standard Deviation 0.374	-0.10 degrees C Standard Deviation 0.387
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 12: 1 H Postdose	0.01 degrees C Standard Deviation 0.364	-0.12 degrees C Standard Deviation 0.359
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 13: Predose	-0.01 degrees C Standard Deviation 0.348	0.04 degrees C Standard Deviation 0.353
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 13: 1 H Postdose	0.03 degrees C Standard Deviation 0.449	0.02 degrees C Standard Deviation 0.418
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 14: Predose	0.06 degrees C Standard Deviation 0.416	-0.01 degrees C Standard Deviation 0.315
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 14: 1 H Postdose	0.06 degrees C Standard Deviation 0.378	0.00 degrees C Standard Deviation 0.419
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Day 15/ET	-0.09 degrees C Standard Deviation 0.320	-0.03 degrees C Standard Deviation 0.391
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Follow-up Day 21	-0.12 degrees C Standard Deviation 0.281	-0.03 degrees C Standard Deviation 0.314
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Follow-up Day 28	-0.04 degrees C Standard Deviation 0.321	-0.07 degrees C Standard Deviation 0.352
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Follow-up Day 35	-0.05 degrees C Standard Deviation 0.324	-0.05 degrees C Standard Deviation 0.359
Change From Baseline (CFB) in Oral Temperature - Part B CFB at Follow-up Day 42	0.03 degrees C Standard Deviation 0.338	-0.08 degrees C Standard Deviation 0.389

SECONDARY outcome

Timeframe: Baseline, Day 1 (0.25, 0.5, 1, 2, 12 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2, 12 hours postdose), Day 8 (predose, 1 hour postdose)

Vital signs measures included supine systolic blood pressure, supine diastolic blood pressure, standing systolic blood pressure, standing diastolic blood pressure, heart rate, respiratory rate, oral temperature, and oxygen saturation. The analysis was performed in participants included in Part B of the study. H = Hour(s). ET = Early Termination.

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 1: 1 H Postdose	-0.1 score on a scale Standard Deviation 0.84	0.2 score on a scale Standard Deviation 1.54
Change From Baseline (CFB) in the SSS Score - Part B Baseline	2.7 score on a scale Standard Deviation 1.47	2.6 score on a scale Standard Deviation 1.31
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 1: 0.25 H Postdose	0.0 score on a scale Standard Deviation 0.94	0.0 score on a scale Standard Deviation 0.82
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 1: 0.5 H Postdose	-0.1 score on a scale Standard Deviation 0.73	0.0 score on a scale Standard Deviation 1.20
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 1: 2 H Postdose	-0.1 score on a scale Standard Deviation 1.26	0.6 score on a scale Standard Deviation 1.70
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 2: Predose	-0.6 score on a scale Standard Deviation 1.19	-0.1 score on a scale Standard Deviation 1.39
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 2: 0.25 H Postdose	-0.5 score on a scale Standard Deviation 1.28	0.1 score on a scale Standard Deviation 1.59
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 2: 0.5 H Postdose	-0.5 score on a scale Standard Deviation 1.13	0.2 score on a scale Standard Deviation 1.62
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 2: 1 H Postdose	-0.3 score on a scale Standard Deviation 1.06	0.5 score on a scale Standard Deviation 1.75
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 2: 2 H Postdose	0.1 score on a scale Standard Deviation 1.29	0.4 score on a scale Standard Deviation 1.73
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 3: Predose	-0.6 score on a scale Standard Deviation 1.14	-0.4 score on a scale Standard Deviation 1.11
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 3: 0.25 H Postdose	-0.7 score on a scale Standard Deviation 1.20	-0.2 score on a scale Standard Deviation 1.45
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 3: 0.5 H Postdose	-0.5 score on a scale Standard Deviation 1.05	-0.1 score on a scale Standard Deviation 1.50
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 3: 1 H Postdose	-0.3 score on a scale Standard Deviation 1.06	0.1 score on a scale Standard Deviation 1.55
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 3: 2 H Postdose	0.0 score on a scale Standard Deviation 1.21	0.5 score on a scale Standard Deviation 1.53
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 4: Predose	-0.7 score on a scale Standard Deviation 1.22	-0.3 score on a scale Standard Deviation 1.39
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 4: 0.25 H Postdose	-0.7 score on a scale Standard Deviation 1.16	-0.2 score on a scale Standard Deviation 1.37
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 4: 0.5 H Postdose	-0.5 score on a scale Standard Deviation 1.19	0.0 score on a scale Standard Deviation 1.42
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 4: 1 H Postdose	-0.4 score on a scale Standard Deviation 1.19	0.0 score on a scale Standard Deviation 1.44
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 4: 2 H Postdose	-0.3 score on a scale Standard Deviation 1.21	0.4 score on a scale Standard Deviation 1.53
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 5: Predose	-1.0 score on a scale Standard Deviation 1.49	-0.5 score on a scale Standard Deviation 1.32
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 5: 0.25 H Postdose	-0.8 score on a scale Standard Deviation 1.41	-0.3 score on a scale Standard Deviation 1.44
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 5: 0.5 H Postdose	-0.8 score on a scale Standard Deviation 1.31	-0.2 score on a scale Standard Deviation 1.29
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 5: 1 H Postdose	-0.6 score on a scale Standard Deviation 1.35	0.2 score on a scale Standard Deviation 1.50
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 5: 2 H Postdose	-0.3 score on a scale Standard Deviation 1.37	0.4 score on a scale Standard Deviation 1.49
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 6: Predose	-0.8 score on a scale Standard Deviation 1.15	-0.5 score on a scale Standard Deviation 1.39
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 6: 0.25 H Postdose	-0.7 score on a scale Standard Deviation 1.20	-0.2 score on a scale Standard Deviation 1.40
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 6: 0.5 H Postdose	-0.6 score on a scale Standard Deviation 1.18	-0.2 score on a scale Standard Deviation 1.39
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 6: 1 H Postdose	-0.4 score on a scale Standard Deviation 1.03	0.1 score on a scale Standard Deviation 1.45
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 6: 2 H Postdose	-0.2 score on a scale Standard Deviation 1.17	0.2 score on a scale Standard Deviation 1.49
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 7: Predose	-0.8 score on a scale Standard Deviation 1.26	-0.6 score on a scale Standard Deviation 1.31
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 7: 0.25 H Postdose	-0.8 score on a scale Standard Deviation 1.25	-0.5 score on a scale Standard Deviation 1.47
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 7: 0.5 H Postdose	-0.6 score on a scale Standard Deviation 1.23	-0.3 score on a scale Standard Deviation 1.30
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 7: 1 H Postdose	-0.4 score on a scale Standard Deviation 1.25	-0.2 score on a scale Standard Deviation 1.36
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 7: 2 H Postdose	-0.2 score on a scale Standard Deviation 1.25	0.1 score on a scale Standard Deviation 1.40
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 8: Predose	-0.8 score on a scale Standard Deviation 1.34	-0.7 score on a scale Standard Deviation 1.36
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 8: 1 H Postdose	-0.6 score on a scale Standard Deviation 1.38	-0.2 score on a scale Standard Deviation 1.65
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 9: Predose	-0.9 score on a scale Standard Deviation 1.38	-0.6 score on a scale Standard Deviation 1.35
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 9: 1 H Postdose	-0.6 score on a scale Standard Deviation 1.23	-0.3 score on a scale Standard Deviation 1.42
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 10: Predose	-1.0 score on a scale Standard Deviation 1.32	-0.6 score on a scale Standard Deviation 1.38
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 10: 1 H Postdose	-0.7 score on a scale Standard Deviation 1.28	-0.3 score on a scale Standard Deviation 1.55
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 11: Predose	-0.7 score on a scale Standard Deviation 1.23	-0.6 score on a scale Standard Deviation 1.36
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 11: 1 H Postdose	-0.6 score on a scale Standard Deviation 1.31	-0.3 score on a scale Standard Deviation 1.68
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 12: Predose	-0.9 score on a scale Standard Deviation 1.25	-0.7 score on a scale Standard Deviation 1.44
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 12: 1 H Postdose	-0.7 score on a scale Standard Deviation 1.30	-0.4 score on a scale Standard Deviation 1.76
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 13: Predose	-0.8 score on a scale Standard Deviation 1.30	-0.8 score on a scale Standard Deviation 1.50
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 13: 1 H Postdose	-0.6 score on a scale Standard Deviation 1.34	-0.4 score on a scale Standard Deviation 1.50
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 14: Predose	-0.7 score on a scale Standard Deviation 1.27	-0.7 score on a scale Standard Deviation 1.35
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 14: 1 H Postdose	-0.5 score on a scale Standard Deviation 1.31	-0.3 score on a scale Standard Deviation 1.46
Change From Baseline (CFB) in the SSS Score - Part B CFB at Day 15	-0.6 score on a scale Standard Deviation 1.50	-0.8 score on a scale Standard Deviation 1.61

SECONDARY outcome

Timeframe: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 3	-5.2 score on a scale Standard Error 1.09	-9.3 score on a scale Standard Error 1.07
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 2	-3.5 score on a scale Standard Error 0.98	-5.8 score on a scale Standard Error 0.97
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 4	-7.7 score on a scale Standard Error 1.13	-10.6 score on a scale Standard Error 1.11
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 5	-8.5 score on a scale Standard Error 1.19	-12.3 score on a scale Standard Error 1.17
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 6	-9.1 score on a scale Standard Error 1.21	-13.6 score on a scale Standard Error 1.19
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 7	-9.2 score on a scale Standard Error 1.29	-13.7 score on a scale Standard Error 1.27
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 8	-11.0 score on a scale Standard Error 1.29	-14.4 score on a scale Standard Error 1.27
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 15	-10.3 score on a scale Standard Error 1.33	-17.4 score on a scale Standard Error 1.31
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 21	-11.3 score on a scale Standard Error 1.43	-16.3 score on a scale Standard Error 1.40
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 28	-11.3 score on a scale Standard Error 1.44	-15.4 score on a scale Standard Error 1.41
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 35	-12.6 score on a scale Standard Error 1.49	-14.9 score on a scale Standard Error 1.47
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B Change from Baseline at Day 42	-12.3 score on a scale Standard Error 1.49	-14.6 score on a scale Standard Error 1.46

SECONDARY outcome

Timeframe: Days 2, 8, 15, 21, 28, 35 and 42

Population: The efficacy set included all participants who were randomized and received at least 1 dose of the double-blind study drug and had a baseline and at least 1 post-baseline efficacy evaluation. Number analyzed: Number of participants in the efficacy set ith a non-missing value at the visit within each treatment group.

HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. The HAM-D total score comprised a sum of 17 individual item scores. Items scored in a range of 0 to 2 included: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following items were scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The total score could range from 0 to 52. Higher scores indicated a greater degree of depression. A negative change from baseline indicated less depression. A positive change from baseline indicated more depression. The analysis was performed in participants included in Part B of the study. Data is reported for participants who had HAM-D response.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Percentage of Participants With HAM-D Response - Part B Day 2	4.5 percentage of participants	15.6 percentage of participants
Percentage of Participants With HAM-D Response - Part B Day 8	47.6 percentage of participants	59.1 percentage of participants
Percentage of Participants With HAM-D Response - Part B Day 15	40.5 percentage of participants	78.6 percentage of participants
Percentage of Participants With HAM-D Response - Part B Day 21	42.1 percentage of participants	73.8 percentage of participants
Percentage of Participants With HAM-D Response - Part B Day 28	46.2 percentage of participants	61.9 percentage of participants
Percentage of Participants With HAM-D Response - Part B Day 35	50.0 percentage of participants	65.9 percentage of participants
Percentage of Participants With HAM-D Response - Part B Day 42	56.4 percentage of participants	61.9 percentage of participants

SECONDARY outcome

Timeframe: Days 2, 8, 15, 21, 28, 35 and 42

Population: The efficacy set included all participants who were randomized and received at least 1 dose of the double-blind study drug and had a baseline and at least 1 post-baseline efficacy evaluation. Number analyzed: Number of participants in efficacy set with a non-missing value at both baseline and the visit within each treatment group.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Percentage of Participants With HAM-D Remission - Part B Day 2	0 percentage of participants	2.2 percentage of participants
Percentage of Participants With HAM-D Remission - Part B Day 8	28.6 percentage of participants	36.4 percentage of participants
Percentage of Participants With HAM-D Remission - Part B Day 15	26.2 percentage of participants	64.3 percentage of participants
Percentage of Participants With HAM-D Remission - Part B Day 21	26.3 percentage of participants	52.4 percentage of participants
Percentage of Participants With HAM-D Remission - Part B Day 28	28.2 percentage of participants	52.4 percentage of participants
Percentage of Participants With HAM-D Remission - Part B Day 35	35.0 percentage of participants	43.9 percentage of participants
Percentage of Participants With HAM-D Remission - Part B Day 42	33.3 percentage of participants	45.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Days 2, 8, 15, 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in the MADRS Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 2	-4.5 score on a scale Standard Error 1.36	-6.9 score on a scale Standard Error 1.35
Change From Baseline in the MADRS Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 8	-15.4 score on a scale Standard Error 1.90	-19.4 score on a scale Standard Error 1.88
Change From Baseline in the MADRS Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 15	-15.0 score on a scale Standard Error 1.94	-22.5 score on a scale Standard Error 1.92
Change From Baseline in the MADRS Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 21	-15.2 score on a scale Standard Error 2.14	-21.9 score on a scale Standard Error 2.11
Change From Baseline in the MADRS Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 28	-14.8 score on a scale Standard Error 2.14	-20.1 score on a scale Standard Error 2.11
Change From Baseline in the MADRS Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 35	-16.4 score on a scale Standard Error 2.25	-19.4 score on a scale Standard Error 2.23
Change From Baseline in the MADRS Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 42	-17.2 score on a scale Standard Error 2.15	-19.1 score on a scale Standard Error 2.11

SECONDARY outcome

Timeframe: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21, 28, 35 and 42

Population: The efficacy set included all participants who were randomized and received at least 1 dose of the double-blind study drug and had a baseline and at least 1 post-baseline efficacy evaluation. Number analyzed: Number of participants in efficacy set with a non-missing value at both baseline and visit within each treatment group.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 2	-6.3 score on a scale Standard Deviation 8.68	-7.8 score on a scale Standard Deviation 12.10
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 35	-29.3 score on a scale Standard Deviation 22.03	-35.0 score on a scale Standard Deviation 21.51
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 42	-30.2 score on a scale Standard Deviation 22.34	-34.7 score on a scale Standard Deviation 22.35
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Baseline	51.1 score on a scale Standard Deviation 6.56	49.4 score on a scale Standard Deviation 5.58
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 3	-9.6 score on a scale Standard Deviation 8.54	-16.0 score on a scale Standard Deviation 15.18
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 4	-14.1 score on a scale Standard Deviation 12.47	-20.4 score on a scale Standard Deviation 16.38
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 5	-17.3 score on a scale Standard Deviation 13.74	-23.2 score on a scale Standard Deviation 15.88
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 6	-18.2 score on a scale Standard Deviation 14.24	-27.5 score on a scale Standard Deviation 16.95
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 7	-19.4 score on a scale Standard Deviation 16.85	-26.3 score on a scale Standard Deviation 16.90
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 8	-24.6 score on a scale Standard Deviation 16.85	-27.9 score on a scale Standard Deviation 16.72
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 15	-22.6 score on a scale Standard Deviation 17.15	-35.1 score on a scale Standard Deviation 14.55
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 21	-23.8 score on a scale Standard Deviation 18.08	-32.5 score on a scale Standard Deviation 16.88
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 28	-24.2 score on a scale Standard Deviation 17.57	-30.8 score on a scale Standard Deviation 17.36
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 35	-25.5 score on a scale Standard Deviation 17.89	-29.5 score on a scale Standard Deviation 18.24
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Meier: Change from Baseline at Day 42	-26.7 score on a scale Standard Deviation 18.21	-29.1 score on a scale Standard Deviation 18.27
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Baseline	47.3 score on a scale Standard Deviation 6.86	46.9 score on a scale Standard Deviation 7.01
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 2	-5.9 score on a scale Standard Deviation 6.84	-7.2 score on a scale Standard Deviation 12.04
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 3	-9.4 score on a scale Standard Deviation 9.16	-14.1 score on a scale Standard Deviation 14.31
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 4	-13.3 score on a scale Standard Deviation 10.85	-18.3 score on a scale Standard Deviation 14.92
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 5	-15.8 score on a scale Standard Deviation 12.39	-21.2 score on a scale Standard Deviation 15.45
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 6	-17.5 score on a scale Standard Deviation 14.04	-25.6 score on a scale Standard Deviation 15.20
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 7	-18.0 score on a scale Standard Deviation 15.97	-24.8 score on a scale Standard Deviation 15.74
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 8	-22.5 score on a scale Standard Deviation 16.28	-26.6 score on a scale Standard Deviation 16.35
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 15	-21.9 score on a scale Standard Deviation 17.94	-33.1 score on a scale Standard Deviation 14.73
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 21	-22.9 score on a scale Standard Deviation 17.77	-30.7 score on a scale Standard Deviation 16.10
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 28	-22.1 score on a scale Standard Deviation 17.42	-29.3 score on a scale Standard Deviation 17.89
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 35	-24.3 score on a scale Standard Deviation 17.34	-28.2 score on a scale Standard Deviation 17.20
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Core: Change from Baseline at Day 42	-25.8 score on a scale Standard Deviation 17.79	-28.0 score on a scale Standard Deviation 18.41
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Baseline	48.1 score on a scale Standard Deviation 13.28	48.8 score on a scale Standard Deviation 11.46
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 2	-8.4 score on a scale Standard Deviation 10.51	-12.8 score on a scale Standard Deviation 12.63
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 3	-12.5 score on a scale Standard Deviation 10.21	-18.9 score on a scale Standard Deviation 15.03
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 4	-17.5 score on a scale Standard Deviation 17.17	-21.8 score on a scale Standard Deviation 16.33
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 5	-18.5 score on a scale Standard Deviation 18.72	-24.1 score on a scale Standard Deviation 15.83
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 6	-18.8 score on a scale Standard Deviation 18.30	-26.5 score on a scale Standard Deviation 17.21
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 7	-19.5 score on a scale Standard Deviation 17.65	-25.4 score on a scale Standard Deviation 17.66
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 8	-21.5 score on a scale Standard Deviation 18.32	-27.9 score on a scale Standard Deviation 17.96
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 15	-20.5 score on a scale Standard Deviation 17.11	-34.1 score on a scale Standard Deviation 16.27
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 21	-23.6 score on a scale Standard Deviation 18.67	-32.7 score on a scale Standard Deviation 17.85
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 28	-23.1 score on a scale Standard Deviation 20.34	-30.8 score on a scale Standard Deviation 16.95
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 35	-24.9 score on a scale Standard Deviation 20.74	-30.0 score on a scale Standard Deviation 17.75
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Anxiety: Change from Baseline at Day 42	-22.9 score on a scale Standard Deviation 21.60	-29.7 score on a scale Standard Deviation 16.57
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Baseline	60.1 score on a scale Standard Deviation 7.12	59.8 score on a scale Standard Deviation 7.23
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 2	-6.8 score on a scale Standard Deviation 9.71	-10.2 score on a scale Standard Deviation 14.55
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 3	-11.3 score on a scale Standard Deviation 9.38	-18.8 score on a scale Standard Deviation 17.93
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 4	-17.0 score on a scale Standard Deviation 13.92	-23.8 score on a scale Standard Deviation 19.11
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 5	-19.5 score on a scale Standard Deviation 16.61	-26.8 score on a scale Standard Deviation 19.32
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 6	-21.4 score on a scale Standard Deviation 16.76	-32.0 score on a scale Standard Deviation 20.13
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 7	-22.8 score on a scale Standard Deviation 18.88	-31.4 score on a scale Standard Deviation 19.69
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 8	-27.5 score on a scale Standard Deviation 19.47	-33.0 score on a scale Standard Deviation 20.08
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 15	-26.3 score on a scale Standard Deviation 21.07	-41.8 score on a scale Standard Deviation 17.78
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 21	-27.9 score on a scale Standard Deviation 20.69	-38.8 score on a scale Standard Deviation 20.80
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B Bech-6: Change from Baseline at Day 28	-27.7 score on a scale Standard Deviation 21.02	-36.1 score on a scale Standard Deviation 21.86

SECONDARY outcome

Timeframe: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21, 28, 35 and 42

Population: The efficacy set included all participants who were randomized and received at least 1 dose of the double-blind study drug and had a baseline and at least 1 post-baseline efficacy evaluation. Number analyzed: Number of participants in efficacy set with a non-missing value at both baseline and the visit within each treatment group.

The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms (GI and general), genital symptoms, loss of weight, and insight. The following symptoms were scored in a range of 0 to 4: agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. Higher scores indicated a greater degree of depression. A negative change from baseline indicated less depression. A positive change from baseline indicated more depression. The analysis was performed in participants included in Part B of the study.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 5	-1.0 score on a scale Standard Deviation 0.88	-1.3 score on a scale Standard Deviation 1.28
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 8	-0.9 score on a scale Standard Deviation 1.01	-1.1 score on a scale Standard Deviation 0.93
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 15	-0.4 score on a scale Standard Deviation 1.01	-1.1 score on a scale Standard Deviation 0.86
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 2	-0.5 score on a scale Standard Deviation 0.95	-0.6 score on a scale Standard Deviation 1.05
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 21	-0.8 score on a scale Standard Deviation 0.88	-1.0 score on a scale Standard Deviation 0.90
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 35	-1.3 score on a scale Standard Deviation 1.31	-1.7 score on a scale Standard Deviation 1.15
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 28	-0.8 score on a scale Standard Deviation 0.96	-0.9 score on a scale Standard Deviation 0.87
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 42	-1.4 score on a scale Standard Deviation 1.29	-1.7 score on a scale Standard Deviation 1.20
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: Baseline	3.1 score on a scale Standard Deviation 0.42	3.1 score on a scale Standard Deviation 0.33
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: Baseline	3.1 score on a scale Standard Deviation 0.56	3.1 score on a scale Standard Deviation 0.32
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 2	-0.3 score on a scale Standard Deviation 0.54	-0.5 score on a scale Standard Deviation 0.84
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 3	-0.5 score on a scale Standard Deviation 0.63	-0.8 score on a scale Standard Deviation 0.90
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 4	-0.7 score on a scale Standard Deviation 0.77	-1.2 score on a scale Standard Deviation 1.09
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 5	-1.0 score on a scale Standard Deviation 0.86	-1.2 score on a scale Standard Deviation 1.10
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 2	-0.3 score on a scale Standard Deviation 0.56	-0.5 score on a scale Standard Deviation 0.89
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 3	-0.5 score on a scale Standard Deviation 0.59	-1.0 score on a scale Standard Deviation 1.18
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 4	-0.9 score on a scale Standard Deviation 0.77	-1.1 score on a scale Standard Deviation 1.12
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 6	-1.2 score on a scale Standard Deviation 0.99	-1.4 score on a scale Standard Deviation 1.27
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 7	-1.1 score on a scale Standard Deviation 1.05	-1.4 score on a scale Standard Deviation 1.20
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 8	-1.4 score on a scale Standard Deviation 1.15	-1.6 score on a scale Standard Deviation 1.22
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 15	-1.5 score on a scale Standard Deviation 1.09	-2.1 score on a scale Standard Deviation 1.18
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 21	-1.5 score on a scale Standard Deviation 1.22	-1.9 score on a scale Standard Deviation 1.09
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 28	-1.6 score on a scale Standard Deviation 1.27	-1.8 score on a scale Standard Deviation 1.22
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 35	-1.7 score on a scale Standard Deviation 1.26	-1.8 score on a scale Standard Deviation 1.31
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Work and Activities: CFB at Day 42	-1.8 score on a scale Standard Deviation 1.29	-1.7 score on a scale Standard Deviation 1.29
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: Baseline	1.7 score on a scale Standard Deviation 0.71	1.7 score on a scale Standard Deviation 0.65
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 2	0.0 score on a scale Standard Deviation 0.82	-0.5 score on a scale Standard Deviation 1.08
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 3	-0.2 score on a scale Standard Deviation 0.92	-0.8 score on a scale Standard Deviation 1.07
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 4	-0.3 score on a scale Standard Deviation 0.80	-0.7 score on a scale Standard Deviation 1.16
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 5	-0.3 score on a scale Standard Deviation 0.88	-1.0 score on a scale Standard Deviation 1.13
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 6	-0.5 score on a scale Standard Deviation 1.00	-1.0 score on a scale Standard Deviation 1.02
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 7	-0.3 score on a scale Standard Deviation 0.94	-1.0 score on a scale Standard Deviation 1.02
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 8	-0.4 score on a scale Standard Deviation 1.01	-1.2 score on a scale Standard Deviation 0.90
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 15	-0.2 score on a scale Standard Deviation 0.96	-1.3 score on a scale Standard Deviation 1.00
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 21	-0.3 score on a scale Standard Deviation 1.14	-1.2 score on a scale Standard Deviation 0.94
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 28	-0.5 score on a scale Standard Deviation 1.17	-1.0 score on a scale Standard Deviation 0.96
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 35	-0.5 score on a scale Standard Deviation 1.13	-1.0 score on a scale Standard Deviation 1.04
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Early: CFB at Day 42	-0.7 score on a scale Standard Deviation 1.13	-0.9 score on a scale Standard Deviation 0.98
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: Baseline	1.8 score on a scale Standard Deviation 0.51	1.7 score on a scale Standard Deviation 0.64
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 2	-0.4 score on a scale Standard Deviation 0.87	-0.5 score on a scale Standard Deviation 0.99
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 3	-0.5 score on a scale Standard Deviation 0.79	-1.0 score on a scale Standard Deviation 0.93
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 4	-0.6 score on a scale Standard Deviation 0.95	-0.9 score on a scale Standard Deviation 0.97
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 5	-0.6 score on a scale Standard Deviation 0.87	-0.9 score on a scale Standard Deviation 1.07
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 6	-0.8 score on a scale Standard Deviation 1.05	-0.9 score on a scale Standard Deviation 1.06
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 7	-0.7 score on a scale Standard Deviation 0.99	-1.0 score on a scale Standard Deviation 0.95
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 15	-0.6 score on a scale Standard Deviation 0.99	-1.2 score on a scale Standard Deviation 0.95
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 21	-0.8 score on a scale Standard Deviation 0.90	-1.2 score on a scale Standard Deviation 0.86
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: Baseline	2.1 score on a scale Standard Deviation 0.70	1.9 score on a scale Standard Deviation 0.83
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 28	-0.8 score on a scale Standard Deviation 0.98	-0.9 score on a scale Standard Deviation 0.96
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 35	-0.9 score on a scale Standard Deviation 1.00	-0.9 score on a scale Standard Deviation 0.98
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Middle: CFB at Day 42	-0.8 score on a scale Standard Deviation 0.94	-1.0 score on a scale Standard Deviation 0.94
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: Baseline	1.6 score on a scale Standard Deviation 0.70	1.5 score on a scale Standard Deviation 0.82
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 3	-0.6 score on a scale Standard Deviation 1.00	-0.7 score on a scale Standard Deviation 1.24
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 4	-0.7 score on a scale Standard Deviation 1.09	-0.7 score on a scale Standard Deviation 1.18
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 5	-0.8 score on a scale Standard Deviation 1.06	-0.8 score on a scale Standard Deviation 1.24
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 6	-0.8 score on a scale Standard Deviation 1.06	-0.9 score on a scale Standard Deviation 1.22
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 7	-0.9 score on a scale Standard Deviation 1.10	-0.8 score on a scale Standard Deviation 1.31
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 8	-0.9 score on a scale Standard Deviation 1.05	-0.9 score on a scale Standard Deviation 1.18
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 15	-0.7 score on a scale Standard Deviation 1.04	-1.1 score on a scale Standard Deviation 1.13
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 21	-0.8 score on a scale Standard Deviation 1.05	-1.0 score on a scale Standard Deviation 1.22
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 28	-0.8 score on a scale Standard Deviation 1.14	-1.0 score on a scale Standard Deviation 1.19
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 35	-1.0 score on a scale Standard Deviation 1.11	-0.9 score on a scale Standard Deviation 1.21
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insomnia Late: CFB at Day 42	-0.9 score on a scale Standard Deviation 1.09	-1.1 score on a scale Standard Deviation 1.01
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: Baseline	1.7 score on a scale Standard Deviation 0.60	1.6 score on a scale Standard Deviation 0.68
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 2	-0.1 score on a scale Standard Deviation 0.50	-0.1 score on a scale Standard Deviation 0.50
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 3	-0.1 score on a scale Standard Deviation 0.42	-0.1 score on a scale Standard Deviation 0.42
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 4	-0.2 score on a scale Standard Deviation 0.57	-0.1 score on a scale Standard Deviation 0.67
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 5	-0.2 score on a scale Standard Deviation 0.51	-0.4 score on a scale Standard Deviation 0.69
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 6	-0.3 score on a scale Standard Deviation 0.61	-0.3 score on a scale Standard Deviation 0.56
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 7	-0.3 score on a scale Standard Deviation 0.58	-0.6 score on a scale Standard Deviation 0.72
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 8	-0.4 score on a scale Standard Deviation 0.67	-0.5 score on a scale Standard Deviation 0.66
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 15	-0.6 score on a scale Standard Deviation 0.79	-0.8 score on a scale Standard Deviation 0.78
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 21	-0.6 score on a scale Standard Deviation 0.89	-0.9 score on a scale Standard Deviation 0.80
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 28	-0.6 score on a scale Standard Deviation 0.78	-0.8 score on a scale Standard Deviation 0.87
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 35	-0.9 score on a scale Standard Deviation 0.94	-1.0 score on a scale Standard Deviation 0.89
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 42	-0.8 score on a scale Standard Deviation 0.92	-0.9 score on a scale Standard Deviation 0.89
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 6	-1.0 score on a scale Standard Deviation 0.99	-1.6 score on a scale Standard Deviation 1.12
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 7	-1.1 score on a scale Standard Deviation 1.14	-1.4 score on a scale Standard Deviation 1.16
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 8	-1.4 score on a scale Standard Deviation 1.25	-1.7 score on a scale Standard Deviation 1.14
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 15	-1.3 score on a scale Standard Deviation 1.23	-2.0 score on a scale Standard Deviation 1.07
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 21	-1.3 score on a scale Standard Deviation 1.34	-1.8 score on a scale Standard Deviation 1.09
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Depressed Mood: CFB at Day 28	-1.3 score on a scale Standard Deviation 1.31	-1.7 score on a scale Standard Deviation 1.22
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 2	-0.1 score on a scale Standard Deviation 0.55	-0.3 score on a scale Standard Deviation 0.60
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 3	-0.3 score on a scale Standard Deviation 0.47	-0.4 score on a scale Standard Deviation 0.66
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 4	-0.5 score on a scale Standard Deviation 0.74	-0.5 score on a scale Standard Deviation 0.73
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 5	-0.5 score on a scale Standard Deviation 0.85	-0.5 score on a scale Standard Deviation 0.89
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 6	-0.6 score on a scale Standard Deviation 0.70	-0.7 score on a scale Standard Deviation 0.89
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 7	-0.6 score on a scale Standard Deviation 0.72	-0.9 score on a scale Standard Deviation 0.76
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 8	-0.6 score on a scale Standard Deviation 0.79	-0.8 score on a scale Standard Deviation 0.86
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: CFB at Day 15	-0.7 score on a scale Standard Deviation 0.91	-1.1 score on a scale Standard Deviation 0.78
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 2	-0.3 score on a scale Standard Deviation 0.69	-0.4 score on a scale Standard Deviation 0.68
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 3	-0.5 score on a scale Standard Deviation 0.73	-0.5 score on a scale Standard Deviation 0.82
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 4	-0.6 score on a scale Standard Deviation 0.87	-0.7 score on a scale Standard Deviation 0.84
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 5	-0.7 score on a scale Standard Deviation 0.76	-1.0 score on a scale Standard Deviation 0.93
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 6	-0.8 score on a scale Standard Deviation 0.97	-1.2 score on a scale Standard Deviation 0.96
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 7	-0.9 score on a scale Standard Deviation 0.99	-1.2 score on a scale Standard Deviation 1.04
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 8	-1.2 score on a scale Standard Deviation 0.91	-1.2 score on a scale Standard Deviation 1.12
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 15	-1.0 score on a scale Standard Deviation 1.15	-1.4 score on a scale Standard Deviation 1.01
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 21	-1.1 score on a scale Standard Deviation 1.04	-1.2 score on a scale Standard Deviation 1.12
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 3	-0.5 score on a scale Standard Deviation 0.90	-0.7 score on a scale Standard Deviation 0.88
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 28	-1.0 score on a scale Standard Deviation 1.03	-1.3 score on a scale Standard Deviation 1.05
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 35	-1.2 score on a scale Standard Deviation 1.00	-1.1 score on a scale Standard Deviation 1.14
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Feelings of Guilt: CFB at Day 42	-1.3 score on a scale Standard Deviation 0.95	-1.2 score on a scale Standard Deviation 1.09
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: Baseline	0.3 score on a scale Standard Deviation 0.51	0.1 score on a scale Standard Deviation 0.29
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 2	-0.2 score on a scale Standard Deviation 0.46	0.0 score on a scale Standard Deviation 0.15
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 3	-0.2 score on a scale Standard Deviation 0.46	0.0 score on a scale Standard Deviation 0.15
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 4	-0.2 score on a scale Standard Deviation 0.45	0.0 score on a scale Standard Deviation 0.21
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 5	-0.2 score on a scale Standard Deviation 0.45	0.0 score on a scale Standard Deviation 0.26
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 6	-0.2 score on a scale Standard Deviation 0.48	0.0 score on a scale Standard Deviation 0.21
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 7	-0.2 score on a scale Standard Deviation 0.48	-0.1 score on a scale Standard Deviation 0.25
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 8	-0.2 score on a scale Standard Deviation 0.51	-0.1 score on a scale Standard Deviation 0.29
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 15	-0.2 score on a scale Standard Deviation 0.52	-0.1 score on a scale Standard Deviation 0.30
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 21	-0.2 score on a scale Standard Deviation 0.54	-0.1 score on a scale Standard Deviation 0.30
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 28	-0.2 score on a scale Standard Deviation 0.52	-0.1 score on a scale Standard Deviation 0.30
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 35	-0.2 score on a scale Standard Deviation 0.52	-0.1 score on a scale Standard Deviation 0.26
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Suicide: CFB at Day 42	-0.2 score on a scale Standard Deviation 0.52	-0.1 score on a scale Standard Deviation 0.30
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: Baseline	2.3 score on a scale Standard Deviation 0.67	2.1 score on a scale Standard Deviation 0.49
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 2	-0.3 score on a scale Standard Deviation 0.78	-0.4 score on a scale Standard Deviation 0.75
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 3	-0.5 score on a scale Standard Deviation 0.66	-0.8 score on a scale Standard Deviation 0.94
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 4	-0.7 score on a scale Standard Deviation 1.05	-1.0 score on a scale Standard Deviation 1.16
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 5	-0.8 score on a scale Standard Deviation 1.05	-1.1 score on a scale Standard Deviation 0.98
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 6	-0.8 score on a scale Standard Deviation 0.91	-1.2 score on a scale Standard Deviation 1.13
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 7	-0.9 score on a scale Standard Deviation 1.01	-1.1 score on a scale Standard Deviation 1.25
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 8	-1.1 score on a scale Standard Deviation 0.97	-1.2 score on a scale Standard Deviation 1.01
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 15	-0.9 score on a scale Standard Deviation 0.93	-1.5 score on a scale Standard Deviation 0.86
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 21	-1.0 score on a scale Standard Deviation 0.90	-1.4 score on a scale Standard Deviation 0.97
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 28	-1.0 score on a scale Standard Deviation 1.00	-1.2 score on a scale Standard Deviation 0.92
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 35	-0.9 score on a scale Standard Deviation 1.13	-1.1 score on a scale Standard Deviation 1.04
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Psychic: CFB at Day 42	-0.9 score on a scale Standard Deviation 1.08	-1.2 score on a scale Standard Deviation 0.83
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: Baseline	1.4 score on a scale Standard Deviation 0.78	1.4 score on a scale Standard Deviation 0.75
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 2	-0.3 score on a scale Standard Deviation 0.61	-0.4 score on a scale Standard Deviation 0.81
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 3	-0.4 score on a scale Standard Deviation 0.75	-0.6 score on a scale Standard Deviation 0.84
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 4	-0.5 score on a scale Standard Deviation 0.88	-0.5 score on a scale Standard Deviation 0.84
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 5	-0.4 score on a scale Standard Deviation 0.87	-0.6 score on a scale Standard Deviation 0.81
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 6	-0.4 score on a scale Standard Deviation 0.87	-0.6 score on a scale Standard Deviation 0.69
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 7	-0.4 score on a scale Standard Deviation 0.91	-0.5 score on a scale Standard Deviation 0.87
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 8	-0.6 score on a scale Standard Deviation 0.99	-0.7 score on a scale Standard Deviation 0.87
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 15	-0.6 score on a scale Standard Deviation 0.80	-0.8 score on a scale Standard Deviation 0.83
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 21	-0.7 score on a scale Standard Deviation 0.92	-0.8 score on a scale Standard Deviation 0.87
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 28	-0.7 score on a scale Standard Deviation 0.90	-0.7 score on a scale Standard Deviation 0.94
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 35	-0.8 score on a scale Standard Deviation 0.80	-0.8 score on a scale Standard Deviation 0.86
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Anxiety Somatic: CFB at Day 42	-0.6 score on a scale Standard Deviation 1.02	-0.8 score on a scale Standard Deviation 0.85
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: Baseline	1.1 score on a scale Standard Deviation 0.85	1.0 score on a scale Standard Deviation 0.83
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 2	-0.2 score on a scale Standard Deviation 0.76	-0.2 score on a scale Standard Deviation 0.67
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 3	-0.3 score on a scale Standard Deviation 0.74	-0.3 score on a scale Standard Deviation 0.84
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 4	-0.5 score on a scale Standard Deviation 0.83	-0.5 score on a scale Standard Deviation 0.82
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 5	-0.5 score on a scale Standard Deviation 0.90	-0.6 score on a scale Standard Deviation 0.78
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 6	-0.5 score on a scale Standard Deviation 1.02	-0.6 score on a scale Standard Deviation 0.80
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 7	-0.5 score on a scale Standard Deviation 1.03	-0.5 score on a scale Standard Deviation 0.84
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 8	-0.5 score on a scale Standard Deviation 1.02	-0.6 score on a scale Standard Deviation 0.87
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 15	-0.5 score on a scale Standard Deviation 0.77	-0.7 score on a scale Standard Deviation 0.91
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 21	-0.5 score on a scale Standard Deviation 0.73	-0.7 score on a scale Standard Deviation 0.81
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 28	-0.5 score on a scale Standard Deviation 0.91	-0.7 score on a scale Standard Deviation 0.92
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 35	-0.6 score on a scale Standard Deviation 0.87	-0.7 score on a scale Standard Deviation 0.94
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Hypochondriasis: CFB at Day 42	-0.6 score on a scale Standard Deviation 0.96	-0.7 score on a scale Standard Deviation 0.92
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: Baseline	0.1 score on a scale Standard Deviation 0.25	0.1 score on a scale Standard Deviation 0.25
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 2	0.0 score on a scale Standard Deviation 0.15	0.0 score on a scale Standard Deviation 0.21
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 3	0.0 score on a scale Standard Deviation 0.21	0.0 score on a scale Standard Deviation 0.26
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 4	0.0 score on a scale Standard Deviation 0.21	0.0 score on a scale Standard Deviation 0.26
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 5	0.0 score on a scale Standard Deviation 0.21	0.0 score on a scale Standard Deviation 0.26
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 6	0.0 score on a scale Standard Deviation 0.21	0.0 score on a scale Standard Deviation 0.26
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 7	0.0 score on a scale Standard Deviation 0.21	0.0 score on a scale Standard Deviation 0.26
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 8	0.0 score on a scale Standard Deviation 0.22	0.0 score on a scale Standard Deviation 0.26
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 15	0.0 score on a scale Standard Deviation 0.22	0.0 score on a scale Standard Deviation 0.22
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 21	-0.1 score on a scale Standard Deviation 0.23	0.0 score on a scale Standard Deviation 0.22
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 28	-0.1 score on a scale Standard Deviation 0.22	0.0 score on a scale Standard Deviation 0.15
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 35	-0.1 score on a scale Standard Deviation 0.22	0.0 score on a scale Standard Deviation 0.16
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Insight: CFB at Day 42	-0.1 score on a scale Standard Deviation 0.22	0.0 score on a scale Standard Deviation 0.22
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: Baseline	0.8 score on a scale Standard Deviation 0.88	0.5 score on a scale Standard Deviation 0.63
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 2	-0.2 score on a scale Standard Deviation 0.73	0.0 score on a scale Standard Deviation 0.52
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 3	-0.2 score on a scale Standard Deviation 0.87	-0.2 score on a scale Standard Deviation 0.53
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 4	-0.2 score on a scale Standard Deviation 0.97	-0.2 score on a scale Standard Deviation 0.53
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 5	-0.4 score on a scale Standard Deviation 0.76	-0.2 score on a scale Standard Deviation 0.61
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 6	-0.3 score on a scale Standard Deviation 0.87	-0.3 score on a scale Standard Deviation 0.60
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 7	-0.3 score on a scale Standard Deviation 0.86	-0.3 score on a scale Standard Deviation 0.60
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 8	-0.5 score on a scale Standard Deviation 0.92	-0.3 score on a scale Standard Deviation 0.64
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 15	-0.4 score on a scale Standard Deviation 0.99	-0.4 score on a scale Standard Deviation 0.66
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 21	-0.4 score on a scale Standard Deviation 0.79	-0.3 score on a scale Standard Deviation 0.65
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 28	-0.6 score on a scale Standard Deviation 1.04	-0.4 score on a scale Standard Deviation 0.59
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 35	-0.6 score on a scale Standard Deviation 0.96	-0.4 score on a scale Standard Deviation 0.63
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Agitation: CFB at Day 42	-0.6 score on a scale Standard Deviation 0.88	-0.3 score on a scale Standard Deviation 0.68
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: Baseline	0.8 score on a scale Standard Deviation 0.89	1.2 score on a scale Standard Deviation 0.97
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 2	-0.1 score on a scale Standard Deviation 0.63	-0.2 score on a scale Standard Deviation 0.83
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 3	-0.2 score on a scale Standard Deviation 0.67	-0.5 score on a scale Standard Deviation 0.87
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 4	-0.3 score on a scale Standard Deviation 0.85	-0.7 score on a scale Standard Deviation 0.95
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 5	-0.3 score on a scale Standard Deviation 0.82	-0.8 score on a scale Standard Deviation 0.96
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 6	-0.3 score on a scale Standard Deviation 0.86	-0.9 score on a scale Standard Deviation 0.99
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 7	-0.4 score on a scale Standard Deviation 0.88	-0.8 score on a scale Standard Deviation 0.90
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 8	-0.4 score on a scale Standard Deviation 0.93	-0.8 score on a scale Standard Deviation 0.93
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 15	-0.4 score on a scale Standard Deviation 0.96	-1.0 score on a scale Standard Deviation 0.91
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 21	-0.4 score on a scale Standard Deviation 0.86	-1.1 score on a scale Standard Deviation 0.93
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 28	-0.4 score on a scale Standard Deviation 0.75	-1.0 score on a scale Standard Deviation 1.02
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 35	-0.5 score on a scale Standard Deviation 0.85	-1.0 score on a scale Standard Deviation 0.94
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Retardation: CFB at Day 42	-0.5 score on a scale Standard Deviation 0.79	-0.9 score on a scale Standard Deviation 0.99
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 35	-0.7 score on a scale Standard Deviation 0.86	-0.8 score on a scale Standard Deviation 0.90
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Genital Symptoms: CFB at Day 42	-0.6 score on a scale Standard Deviation 0.88	-0.7 score on a scale Standard Deviation 0.86
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: Baseline	1.3 score on a scale Standard Deviation 0.79	1.5 score on a scale Standard Deviation 0.76
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 2	-0.1 score on a scale Standard Deviation 0.69	-0.4 score on a scale Standard Deviation 0.62
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 3	-0.2 score on a scale Standard Deviation 0.64	-0.6 score on a scale Standard Deviation 0.77
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 4	-0.4 score on a scale Standard Deviation 0.82	-0.7 score on a scale Standard Deviation 0.73
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 5	-0.5 score on a scale Standard Deviation 0.98	-0.8 score on a scale Standard Deviation 0.77
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 6	-0.5 score on a scale Standard Deviation 0.95	-0.8 score on a scale Standard Deviation 0.85
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 7	-0.4 score on a scale Standard Deviation 1.00	-0.9 score on a scale Standard Deviation 0.89
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 8	-0.5 score on a scale Standard Deviation 0.94	-0.9 score on a scale Standard Deviation 0.95
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 21	-0.6 score on a scale Standard Deviation 0.95	-1.1 score on a scale Standard Deviation 0.89
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 28	-0.6 score on a scale Standard Deviation 0.91	-1.0 score on a scale Standard Deviation 0.92
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 35	-0.7 score on a scale Standard Deviation 0.94	-1.0 score on a scale Standard Deviation 0.89
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms GI: CFB at Day 42	-0.7 score on a scale Standard Deviation 0.77	-0.9 score on a scale Standard Deviation 0.84
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: Baseline	0.9 score on a scale Standard Deviation 0.87	1.1 score on a scale Standard Deviation 0.86
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 2	-0.5 score on a scale Standard Deviation 0.73	-0.5 score on a scale Standard Deviation 0.79
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 4	-0.5 score on a scale Standard Deviation 0.91	-0.7 score on a scale Standard Deviation 1.00
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 5	-0.6 score on a scale Standard Deviation 0.97	-0.7 score on a scale Standard Deviation 0.86
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 6	-0.6 score on a scale Standard Deviation 0.90	-0.8 score on a scale Standard Deviation 0.93
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 7	-0.7 score on a scale Standard Deviation 0.87	-0.7 score on a scale Standard Deviation 0.94
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 8	-0.6 score on a scale Standard Deviation 0.94	-0.8 score on a scale Standard Deviation 0.91
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 15	-0.7 score on a scale Standard Deviation 0.93	-0.8 score on a scale Standard Deviation 0.88
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 21	-0.7 score on a scale Standard Deviation 0.93	-0.9 score on a scale Standard Deviation 0.88
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 28	-0.6 score on a scale Standard Deviation 0.97	-1.0 score on a scale Standard Deviation 0.88
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 35	-0.7 score on a scale Standard Deviation 0.97	-0.9 score on a scale Standard Deviation 0.90
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Loss of Weight: CFB at Day 42	-0.6 score on a scale Standard Deviation 0.88	-0.9 score on a scale Standard Deviation 0.95
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B Somatic Symptoms General: Baseline	1.7 score on a scale Standard Deviation 0.50	1.7 score on a scale Standard Deviation 0.46

SECONDARY outcome

Timeframe: Baseline, Days 2, 8, 15, 21, 28, 35 and 42

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline in HAM-A Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 2	-3.7 score on a scale Standard Error 0.86	-5.5 score on a scale Standard Error 0.83
Change From Baseline in HAM-A Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 8	-8.9 score on a scale Standard Error 1.09	-11.4 score on a scale Standard Error 1.06
Change From Baseline in HAM-A Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 15	-8.6 score on a scale Standard Error 1.11	-13.2 score on a scale Standard Error 1.08
Change From Baseline in HAM-A Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 21	-9.5 score on a scale Standard Error 1.25	-12.9 score on a scale Standard Error 1.21
Change From Baseline in HAM-A Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 28	-10.0 score on a scale Standard Error 1.26	-12.2 score on a scale Standard Error 1.22
Change From Baseline in HAM-A Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 35	-9.9 score on a scale Standard Error 1.38	-12.0 score on a scale Standard Error 1.35
Change From Baseline in HAM-A Total Score at Day 15 and All Other Time Points - Part B Change from Baseline at Day 42	-9.6 score on a scale Standard Error 1.39	-11.8 score on a scale Standard Error 1.35

SECONDARY outcome

Timeframe: Days 2, 8, 15, 21, 28, 35 and 42

Population: The efficacy set included all participants who were randomized and received at least 1 dose of the double-blind study drug and had a baseline and at least 1 post-baseline efficacy evaluation. Number analyzed: Number of participants in efficacy set with a non-missing value at both baseline and the visit within each treatment group.

The CGI-I item employed a 7-point Likert scale to measure the overall improvement in the participant's condition post-treatment. The investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The CGI-I was only rated at post-treatment assessments. By definition, all CGI-I assessments were evaluated against baseline conditions. CGI-I response was defined as having a score of 1 (very much improved) or 2 (much improved). The analysis was performed in participants included in Part B of the study. Data is reported for participants who had CGI-I response.

Outcome measures

Outcome measures
Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Percentage of Participants With CGI-I Response - Part B Day 2	0 percentage of participants	15.6 percentage of participants
Percentage of Participants With CGI-I Response - Part B Day 8	45.2 percentage of participants	70.5 percentage of participants
Percentage of Participants With CGI-I Response - Part B Day 15	45.2 percentage of participants	78.6 percentage of participants
Percentage of Participants With CGI-I Response - Part B Day 21	50.0 percentage of participants	71.4 percentage of participants
Percentage of Participants With CGI-I Response - Part B Day 28	46.2 percentage of participants	66.7 percentage of participants
Percentage of Participants With CGI-I Response - Part B Day 35	55.0 percentage of participants	63.4 percentage of participants
Percentage of Participants With CGI-I Response - Part B Day 42	59.0 percentage of participants	69.0 percentage of participants

Adverse Events

Part A: SAGE-217

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Part B: Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Part B: SAGE-217

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Part A: SAGE-217 n=44 Participants Participants received SAGE-217, 30 mg, oral solution, once daily for 14 days, as tolerated.	Part B: SAGE-217 n=45 Participants Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Change From Baseline (CFB) in Oxygen Saturation - Part B Baseline	97.95 percentage of oxygen saturation Standard Deviation 1.509	98.02 percentage of oxygen saturation Standard Deviation 1.485
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 1: 0.25 H Postdose	-0.11 percentage of oxygen saturation Standard Deviation 1.768	-0.02 percentage of oxygen saturation Standard Deviation 1.502
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 1: 0.5 H Postdose	0.12 percentage of oxygen saturation Standard Deviation 1.384	0.00 percentage of oxygen saturation Standard Deviation 1.510
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 1: 1 H Postdose	0.02 percentage of oxygen saturation Standard Deviation 1.470	-0.39 percentage of oxygen saturation Standard Deviation 1.401
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 1: 2 H Postdose	0.11 percentage of oxygen saturation Standard Deviation 1.513	-0.32 percentage of oxygen saturation Standard Deviation 1.459
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 1: 12 H Postdose	0.09 percentage of oxygen saturation Standard Deviation 1.789	-0.24 percentage of oxygen saturation Standard Deviation 1.827
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 2: Predose	-0.23 percentage of oxygen saturation Standard Deviation 1.939	-0.29 percentage of oxygen saturation Standard Deviation 1.576
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 2: 0.25 H Postdose	-0.23 percentage of oxygen saturation Standard Deviation 1.915	-0.22 percentage of oxygen saturation Standard Deviation 1.475
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 2: 0.5 H Postdose	-0.20 percentage of oxygen saturation Standard Deviation 2.041	-0.44 percentage of oxygen saturation Standard Deviation 1.726
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 2: 1 H Postdose	-0.09 percentage of oxygen saturation Standard Deviation 1.902	-0.38 percentage of oxygen saturation Standard Deviation 1.762
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 2: 2 H Postdose	-0.11 percentage of oxygen saturation Standard Deviation 1.907	-0.36 percentage of oxygen saturation Standard Deviation 1.654
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 2: 12 H Postdose	-0.34 percentage of oxygen saturation Standard Deviation 5.278	-0.47 percentage of oxygen saturation Standard Deviation 2.599
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 3: Predose	-0.32 percentage of oxygen saturation Standard Deviation 1.827	-0.29 percentage of oxygen saturation Standard Deviation 1.766
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 3: 0.25 H Postdose	-0.09 percentage of oxygen saturation Standard Deviation 1.789	-0.32 percentage of oxygen saturation Standard Deviation 1.695
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 3: 0.5 H Postdose	-0.11 percentage of oxygen saturation Standard Deviation 1.742	-0.42 percentage of oxygen saturation Standard Deviation 1.712
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 3: 1 H Postdose	-0.27 percentage of oxygen saturation Standard Deviation 1.860	-0.44 percentage of oxygen saturation Standard Deviation 1.902
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 3: 2 H Postdose	-0.32 percentage of oxygen saturation Standard Deviation 2.340	-0.78 percentage of oxygen saturation Standard Deviation 1.894
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 3: 12 H Postdose	0.14 percentage of oxygen saturation Standard Deviation 1.959	-0.24 percentage of oxygen saturation Standard Deviation 1.824
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 4: Predose	-0.20 percentage of oxygen saturation Standard Deviation 1.579	-0.27 percentage of oxygen saturation Standard Deviation 1.643
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 4: 0.25 H Postdose	0.09 percentage of oxygen saturation Standard Deviation 1.709	-0.24 percentage of oxygen saturation Standard Deviation 1.667
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 4: 0.5 H Postdose	-0.20 percentage of oxygen saturation Standard Deviation 1.720	-0.33 percentage of oxygen saturation Standard Deviation 1.581
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 4: 1 H Postdose	-0.41 percentage of oxygen saturation Standard Deviation 1.933	-0.29 percentage of oxygen saturation Standard Deviation 1.646
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 4: 2 H Postdose	-0.70 percentage of oxygen saturation Standard Deviation 2.018	-1.16 percentage of oxygen saturation Standard Deviation 2.667
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 4: 12 H Postdose	0.00 percentage of oxygen saturation Standard Deviation 2.000	-1.31 percentage of oxygen saturation Standard Deviation 4.986
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 5: Predose	-0.16 percentage of oxygen saturation Standard Deviation 1.539	-0.36 percentage of oxygen saturation Standard Deviation 2.165
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 5: 0.25 H Postdose	0.20 percentage of oxygen saturation Standard Deviation 1.407	-0.58 percentage of oxygen saturation Standard Deviation 2.179
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 5: 0.5 H Postdose	-0.09 percentage of oxygen saturation Standard Deviation 1.736	-0.49 percentage of oxygen saturation Standard Deviation 2.564
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 5: 1 H Postdose	-0.07 percentage of oxygen saturation Standard Deviation 2.161	-0.61 percentage of oxygen saturation Standard Deviation 2.895
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 5: 2 H Postdose	-0.05 percentage of oxygen saturation Standard Deviation 1.765	-0.62 percentage of oxygen saturation Standard Deviation 2.338
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 5: 12 H Postdose	0.11 percentage of oxygen saturation Standard Deviation 1.979	0.09 percentage of oxygen saturation Standard Deviation 1.856
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 6: Predose	-0.02 percentage of oxygen saturation Standard Deviation 1.933	-0.13 percentage of oxygen saturation Standard Deviation 1.424
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 6: 0.25 H Postdose	0.09 percentage of oxygen saturation Standard Deviation 1.525	-0.02 percentage of oxygen saturation Standard Deviation 1.631
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 6: 0.5 H Postdose	0.12 percentage of oxygen saturation Standard Deviation 1.749	0.16 percentage of oxygen saturation Standard Deviation 1.147
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 6: 1 H Postdose	0.09 percentage of oxygen saturation Standard Deviation 1.849	-0.22 percentage of oxygen saturation Standard Deviation 1.820
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 6: 2 H Postdose	-0.07 percentage of oxygen saturation Standard Deviation 1.920	0.16 percentage of oxygen saturation Standard Deviation 1.492
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 6: 12 H Postdose	0.37 percentage of oxygen saturation Standard Deviation 1.852	0.02 percentage of oxygen saturation Standard Deviation 1.672
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 7: Predose	-0.31 percentage of oxygen saturation Standard Deviation 1.932	-0.16 percentage of oxygen saturation Standard Deviation 1.656
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 7: 0.25 H Postdose	0.05 percentage of oxygen saturation Standard Deviation 2.129	0.07 percentage of oxygen saturation Standard Deviation 1.516
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 7: 0.5 H Postdose	-0.21 percentage of oxygen saturation Standard Deviation 2.007	-0.16 percentage of oxygen saturation Standard Deviation 1.928
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 7: 1 H Postdose	-0.05 percentage of oxygen saturation Standard Deviation 1.987	-0.45 percentage of oxygen saturation Standard Deviation 1.663
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 7: 2 H Postdose	0.17 percentage of oxygen saturation Standard Deviation 1.987	-0.55 percentage of oxygen saturation Standard Deviation 2.757
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 7: 12 H Postdose	0.31 percentage of oxygen saturation Standard Deviation 2.089	-0.11 percentage of oxygen saturation Standard Deviation 1.833
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 8: Predose	0.21 percentage of oxygen saturation Standard Deviation 1.510	-0.26 percentage of oxygen saturation Standard Deviation 1.499
Change From Baseline (CFB) in Oxygen Saturation - Part B CFB at Day 8: 1 H Postdose	0.08 percentage of oxygen saturation Standard Deviation 2.005	-0.67 percentage of oxygen saturation Standard Deviation 1.789