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A Study to Evaluate SAGE-217 in Participants With Moderate to Severe Major Depressive Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03000530
Recruitment Status : Completed
First Posted : December 22, 2016
Results First Posted : December 2, 2020
Last Update Posted : December 2, 2020
Sponsor:
Information provided by (Responsible Party):
Sage Therapeutics

Brief Summary:
This is a two-part (open-label followed by double-blind) study evaluating the safety, tolerability, pharmacokinetics, and efficacy of SAGE-217 in 102 participants diagnosed with moderate to severe Major Depressive Disorder.

Condition or disease Intervention/treatment Phase
Major Depression Drug: SAGE-217 Drug: Placebo Phase 2

Detailed Description:

Part A of the study is an open-label design with dosing of SAGE-217 for 14 days.

Part B of the study is a randomized, double-blind, parallel-group, placebo-controlled design. Eligible participants were randomized to SAGE-217 or placebo for 14 days.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 102 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Two-Part (Open-Label Followed by Double-Blind) Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of SAGE-217 in the Treatment of Adult Subjects With Moderate to Severe Major Depressive Disorder
Actual Study Start Date : December 7, 2016
Actual Primary Completion Date : October 4, 2017
Actual Study Completion Date : November 8, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A: SAGE-217
Participants received SAGE-217, 30 milligrams (mg), oral solution, once daily for 14 days, as tolerated.
Drug: SAGE-217
Placebo Comparator: Part B: Placebo
Eligible participants received matching placebo capsules once daily for 14 days.
Drug: Placebo
Experimental: Part B: SAGE-217
Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.
Drug: SAGE-217



Primary Outcome Measures :
  1. Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) - Part A [ Time Frame: Day 1 up to Day 21 ]
    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.

  2. Percentage of Participants With TEAEs, Graded by Severity - Part A [ Time Frame: Day 1 up to Day 21 ]
    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.

  3. Change From Baseline in Basophils - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  4. Change From Baseline in Basophils to Leukocytes Ratio [Percentage (%)] - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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. The blood cell differential (ratio) data are presented as International System (SI) unit, percentage (%).

  5. Change From Baseline in Eosinophils - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  6. Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

  7. Change From Baseline in Hematocrit - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  8. Change From Baseline in Hemoglobin - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  9. Change From Baseline in Lymphocytes - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  10. Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

  11. Change From Baseline in Monocytes - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  12. Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

  13. Change From Baseline in Neutrophils - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  14. Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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. The blood cell differential (ratio) data are presented as SI unit, percentage (%).

  15. Change From Baseline in Platelets - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  16. Change From Baseline in Erythrocytes - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  17. Change From Baseline in Reticulocytes - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  18. Change From Baseline in Leukocytes - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  19. Change From Baseline in Albumin - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  20. Change From Baseline in Alkaline Phosphatase - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  21. Change From Baseline in Alanine Aminotransferase - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  22. Change From Baseline in Aspartate Aminotransferase - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  23. Change From Baseline in Bilirubin - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  24. Change From Baseline in Chloride - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  25. Change From Baseline in Carbon Dioxide - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  26. Change From Baseline in Creatinine - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  27. Change From Baseline in Potassium - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  28. Change From Baseline in Protein - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  29. Change From Baseline in Sodium - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  30. Change From Baseline in Urea Nitrogen - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  31. Change From Baseline in Activated Partial Thromboplastin Time - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  32. Change From Baseline in Prothrombin International Normalized Ratio (%) - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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. The data for prothrombin international normalized ratio are presented as SI unit, percentage (%).

  33. Change From Baseline in Prothrombin Time - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    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.

  34. Change From Baseline in pH - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

  35. Change From Baseline in Specific Gravity - Part A [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28 ]
    Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part A of the study. ET = Early Termination.

  36. Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A [ Time Frame: 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 ]
    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.

  37. Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A [ Time Frame: 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 ]
    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.

  38. Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A [ Time Frame: 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 ]
    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.

  39. Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A [ Time Frame: 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 ]
    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.

  40. Change From Baseline (CFB) in Heart Rate - Part A [ Time Frame: 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 ]
    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.

  41. Change From Baseline (CFB) in Respiratory Rate - Part A [ Time Frame: 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 ]
    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.

  42. Change From Baseline (CFB) in Oral Temperature - Part A [ Time Frame: 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 ]
    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.

  43. Change From Baseline (CFB) in Oxygen Saturation - Part A [ Time Frame: 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 A of the study. H = Hour(s).

  44. Change From Baseline in QT Interval - Part A [ Time Frame: 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.

  45. Change From Baseline in QTcF Interval - Part A [ Time Frame: 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.

  46. Change From Baseline in ECG Mean Heart Rate - Part A [ Time Frame: 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.

  47. Change From Baseline in RR Interval - Part A [ Time Frame: 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.

  48. Change From Baseline in PR Interval - Part A [ Time Frame: 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.

  49. Change From Baseline in QRS Interval - Part A [ Time Frame: 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.

  50. Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item - Part A [ Time Frame: Day 1 up to Day 28 ]
    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.

  51. Change From Baseline in Stanford Sleepiness Scale (SSS) Score at Day 15 - Part A [ Time Frame: Baseline, Day 15 ]
    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.

  52. Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 - Part B [ Time Frame: 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.


Secondary Outcome Measures :
  1. Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A [ Time Frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28 ]
    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.

  2. Percentage of Participants With TEAEs - Part B [ Time Frame: Day 1 up to Day 21 ]
    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.

  3. Percentage of Participants With AEs During Post-TEAE Period [ Time Frame: Day 21 up to Day 42 ]
    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.

  4. Percentage of Participants With TEAEs, Graded by Severity - Part B [ Time Frame: Day 1 up to Day 21 ]
    Severity was assessed according to the following scale: mild (awareness of sign or symptom, but easily tolerated); moderate (discomfort sufficient to cause interference with normal activities); severe (incapacitating, with inability to perform normal activities). The analysis was performed in participants included in Part B of the study.

  5. Change From Baseline in Basophils - Part B [ Time Frame: 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.

  6. Change From Baseline in Basophils to Leukocytes Ratio (%) - Part B [ Time Frame: 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 (%).

  7. Change From Baseline in Eosinophils - Part B [ Time Frame: 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.

  8. Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part B [ Time Frame: 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 (%).

  9. Change From Baseline in Hematocrit - Part B [ Time Frame: 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.

  10. Change From Baseline in Hemoglobin - Part B [ Time Frame: 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.

  11. Change From Baseline in Lymphocytes - Part B [ Time Frame: 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.

  12. Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part B [ Time Frame: 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 (%).

  13. Change From Baseline in Monocytes - Part B [ Time Frame: 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.

  14. Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part B [ Time Frame: 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 (%).

  15. Change From Baseline in Neutrophils - Part B [ Time Frame: 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.

  16. Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part B [ Time Frame: 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 (%).

  17. Change From Baseline in Platelets - Part B [ Time Frame: 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.

  18. Change From Baseline in Erythrocytes - Part B [ Time Frame: 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.

  19. Change From Baseline in Reticulocytes - Part B [ Time Frame: Baseline, Day 8, Day 15/ET ]
    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.

  20. Change From Baseline in Reticulocytes to Erythrocytes Ratio (%) - Part B [ Time Frame: 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 (%).

  21. Change From Baseline in Leukocytes - Part B [ Time Frame: 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.

  22. Change From Baseline in Albumin - Part B [ Time Frame: 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.

  23. Change From Baseline in Alkaline Phosphatase - Part B [ Time Frame: 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.

  24. Change From Baseline in Alanine Aminotransferase - Part B [ Time Frame: 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.

  25. Change From Baseline in Aspartate Aminotransferase - Part B [ Time Frame: 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.

  26. Change From Baseline in Bilirubin - Part B [ Time Frame: 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.

  27. Change From Baseline in Calcium - Part B [ Time Frame: 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.

  28. Change From Baseline in Chloride - Part B [ Time Frame: 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.

  29. Change From Baseline in Carbon Dioxide - Part B [ Time Frame: 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.

  30. Change From Baseline in Creatinine - Part B [ Time Frame: 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.

  31. Change From Baseline in Glucose - Part B [ Time Frame: 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.

  32. Change From Baseline in Potassium - Part B [ Time Frame: 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.

  33. Change From Baseline in Magnesium - Part B [ Time Frame: 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.

  34. Change From Baseline in Phosphate - Part B [ Time Frame: 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.

  35. Change From Baseline in Protein - Part B [ Time Frame: 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.

  36. Change From Baseline in Sodium - Part B [ Time Frame: 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.

  37. Change From Baseline in Thyrotropin - Part B [ Time Frame: 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.

  38. Change From Baseline in Urea Nitrogen - Part B [ Time Frame: 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.

  39. Change From Baseline in Activated Partial Thromboplastin Time - Part B [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42 ]
    Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio, and prothrombin time. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

  40. Change From Baseline in Prothrombin International Normalized Ratio (%) - Part B [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42 ]
    Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio, and prothrombin time. The analysis was performed in participants included in Part B of the study. ET = Early Termination. The data for prothrombin international normalized ratio are presented as SI unit, percentage (%).

  41. Change From Baseline in Prothrombin Time - Part B [ Time Frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42 ]
    Coagulation measures included activated partial thromboplastin time, prothrombin international normalized ratio, and prothrombin time. The analysis was performed in participants included in Part B of the study. ET = Early Termination.

  42. Change From Baseline in pH - Part B [ Time Frame: 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.

  43. Change From Baseline in Specific Gravity - Part B [ Time Frame: 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.

  44. Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B [ Time Frame: 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 Days 21, 28, 35 and 42 ]
    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.

  45. Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B [ Time Frame: 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 Days 21, 28, 35 and 42 ]
    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.

  46. Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B [ Time Frame: 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 Days 21, 28, 35 and 42 ]
    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.

  47. Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B [ Time Frame: 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 Days 21, 28, 35 and 42 ]
    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.

  48. Change From Baseline (CFB) in Heart Rate - Part B [ Time Frame: 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 Days 21, 28, 35 and 42 ]
    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.

  49. Change From Baseline (CFB) in Respiratory Rate - Part B [ Time Frame: 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 Days 21, 28, 35 and 42 ]
    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.

  50. Change From Baseline (CFB) in Oral Temperature - Part B [ Time Frame: 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 Days 21, 28, 35 and 42 ]
    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.

  51. Change From Baseline (CFB) in Oxygen Saturation - Part B [ Time Frame: 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.

  52. Change From Baseline in QT Interval - Part B [ Time Frame: 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 B of the study.

  53. Change From Baseline in QTcF Interval - Part B [ Time Frame: 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 B of the study.

  54. Change From Baseline in ECG Mean Heart Rate - Part B [ Time Frame: 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 B of the study.

  55. Change From Baseline in RR Interval - Part B [ Time Frame: 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 B of the study.

  56. Change From Baseline in PR Interval - Part B [ Time Frame: 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 B of the study.

  57. Change From Baseline in QRS Duration - Part B [ Time Frame: 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 B of the study.

  58. Percentage of Participants With a Response of "Yes" to Any C-SSRS Suicidal Ideation (SI) Item - Part B [ Time Frame: Screening, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 21, 28, 35 and 42 ]
    The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation 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 B of the study. SCLR = screening: lifetime recall.

  59. Percentage of Participants With HAM-D Response - Part A [ Time Frame: Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28 ]
    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 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. Data is reported for participants who had HAM-D response.

  60. Percentage of Participants With HAM-D Remission - Part A [ Time Frame: Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28 ]
    HAM-D remission was defined as having a HAM-D total score of ≤7. The HAM-D total score comprised a sum of the 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 A of the study.

  61. Change From Baseline in the Montgomery and Åsberg Depression Rating Scale (MADRS) Total Score at Day 15 and All Other Time Points - Part A [ Time Frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28 ]
    The MADRS was a ten-item diagnostic questionnaire which psychiatrists used to measure the severity of depressive episodes in participants with mood disorders. It was designed as an adjunct to the HAM-D, to be more sensitive than the Hamilton Scale to the changes brought on by antidepressants and other forms of treatment. Each item yielded a score of 0 to 6. The MADRS total score was calculated as the sum of the 10 individual item scores, which ranged from 0 to 60. Higher MADRS scores indicated more severe depression. A negative change from baseline indicated less severe depression. A positive change from baseline indicated more severe depression. The analysis was performed in participants included in Part A of the study.

  62. Change From Baseline in HAM-D Subscale Scores at Day 15 and All Other Time Points - Part A [ Time Frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28 ]
    HAM-D subscales were: Core, symptoms: depressed mood (DM), feelings of guilt (FG), suicide, work and activities (WA), and retardation (RE); Anxiety, symptoms: anxiety (psychic and somatic), somatic symptoms (SS) (gastrointestinal and general), hypochondriasis, and loss of weight; Bech-6, symptoms: DM, FG, WA, RE, anxiety psychic (AP), and SS general; and Maier, symptoms: DM, FG, WA, RE, agitation, and AP. Each item was scored in a range of 0 to 2 or 0 to 4. Higher scores indicated a greater degree of depression. Subscale scores were calculated as sum of individual rating scores related to each subscale, divided by total possible score within subscale, multiplied by 100, and rounded to a whole number. Therefore, subscale scores would be within range of 0-100 and might be larger than total score. 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 study.

  63. Change From Baseline (CFB) in HAM-D Individual Item Scores at Day 15 and All Other Time Points - Part A [ Time Frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28 ]
    The HAM-D comprised individual ratings of the following symptoms scored in a range of 0 to 2: insomnia (early, middle, late), somatic symptoms [gastrointestinal (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 A of the study.

  64. Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at All Time Points - Part A [ Time Frame: Baseline, Days 2, 3, 8, 15, 21 and 28 ]
    The 14-item HAM-A was used to rate the severity of symptoms of anxiety. Each of the 14 items was defined by a series of symptoms, and measured both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Scoring for HAM-A was calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56, where 0-13=Normal, 14-17 Mild Anxiety, 18-24 Moderate Anxiety, >=25 Severe Anxiety, per the Psych Congress Network. The HAM-A total score was calculated as the sum of the 14 individual item scores. A negative change from baseline indicated less anxiety. A positive change from baseline indicated more anxiety. The analysis was performed in participants included in Part A of the study.

  65. Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response - Part A [ Time Frame: Days 2, 3, 8, 15, 21 and 28 ]
    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 CGI-I global improvement score of 1 (very much improved) or 2 (much improved). The analysis was performed in participants included in Part A of the study. Data is reported for participants who had CGI-I response.

  66. Change From Baseline (CFB) in the SSS Score - Part B [ Time Frame: Baseline, Day 1 (0.25, 0.5, 1, 2 hours postdose), Days 2, 3, 4, 5, 6 and 7 (predose, 0.25, 0.5, 1, 2 hours postdose), Days 8, 9, 10, 11, 12, 13 and 14 (predose, 1 hour postdose), Day 15 ]
    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 B of the study. H = Hour(s).

  67. Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B [ Time Frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21, 28, 35 and 42 ]
    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.

  68. Percentage of Participants With HAM-D Response - Part B [ Time Frame: Days 2, 8, 15, 21, 28, 35 and 42 ]
    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.

  69. Percentage of Participants With HAM-D Remission - Part B [ Time Frame: Days 2, 8, 15, 21, 28, 35 and 42 ]
    HAM-D remission was defined as having a HAM-D total score of ≤7. The HAM-D total score comprised a sum of the 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.

  70. Change From Baseline in the MADRS Total Score at Day 15 and All Other Time Points - Part B [ Time Frame: Baseline, Days 2, 8, 15, 21, 28, 35 and 42 ]
    The MADRS was a ten-item diagnostic questionnaire which psychiatrists used to measure the severity of depressive episodes in participants with mood disorders. It was designed as an adjunct to the HAM-D, to be more sensitive than the Hamilton Scale to the changes brought on by antidepressants and other forms of treatment. Each item yielded a score of 0 to 6. The MADRS total score was calculated as the sum of the 10 individual item scores, which ranged from 0 to 60. Higher MADRS scores indicated more severe depression. A negative change from baseline indicated less severe depression. A positive change from baseline indicated more severe depression. The analysis was performed in participants included in Part B of the study.

  71. Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B [ Time Frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21, 28, 35 and 42 ]
    HAM-D subscales were: Core, symptoms: depressed mood (DM), feelings of guilt (FG), suicide, work and activities (WA), and retardation (RE); Anxiety, symptoms: anxiety (psychic and somatic), somatic symptoms (SS) (gastrointestinal and general), hypochondriasis, and loss of weight; Bech-6, symptoms: DM, FG, WA, RE, anxiety psychic (AP), and SS general; and Maier, symptoms: DM, FG, WA, RE, agitation, and AP. Each item was scored in a range of 0 to 2 or 0 to 4. Higher scores indicated a greater degree of depression. Subscale scores were calculated as sum of individual rating scores related to each subscale, divided by total possible score within subscale, multiplied by 100, and rounded to a whole number. Therefore, subscale scores would be within range of 0-100 and might be larger than total score. 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 study.

  72. Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B [ Time Frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21, 28, 35 and 42 ]
    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.

  73. Change From Baseline in HAM-A Total Score at Day 15 and All Other Time Points - Part B [ Time Frame: Baseline, Days 2, 8, 15, 21, 28, 35 and 42 ]
    The 14-item HAM-A was used to rate the severity of symptoms of anxiety. Each of the 14 items was defined by a series of symptoms, and measured both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Scoring for HAM-A was calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56, where 0-13=Normal, 14-17 Mild Anxiety, 18-24 Moderate Anxiety, >=25 Severe Anxiety, per the Psych Congress Network. The HAM-A total score was calculated as the sum of the 14 individual item scores. A negative change from baseline indicated less anxiety. A positive change from baseline indicated more anxiety. The analysis was performed in participants included in Part B of the study.

  74. Percentage of Participants With CGI-I Response - Part B [ Time Frame: Days 2, 8, 15, 21, 28, 35 and 42 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant has a diagnosis of Major Depressive Disorder that has been present for at least a 4-week period as diagnosed by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I)

Exclusion Criteria:

  • Participant has a history of suicide attempt
  • Participant has a history of treatment-resistant depression, defined as persistent depressive symptoms despite treatment with adequate doses of antidepressants from two different classes for an adequate amount of time
  • Participant has active psychosis
  • Participant has a medical history of seizures
  • Participant has a medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03000530


Locations
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United States, California
Sage Investigational Site
Garden Grove, California, United States, 92845
United States, Florida
Sage Investigational Site
Orlando, Florida, United States, 32806
United States, Georgia
Sage Investigational Site
Atlanta, Georgia, United States, 30331
United States, Louisiana
Sage Investigational Site
Lake Charles, Louisiana, United States, 70629
United States, New Jersey
Sage Investigational Site
Berlin, New Jersey, United States, 08009
United States, Ohio
Sage Investigational Site
Dayton, Ohio, United States, 45417
United States, Texas
Sage Investigational Site
Austin, Texas, United States, 78754
United States, Virginia
Sage Investigational Site
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Sage Therapeutics
Investigators
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Study Director: Christopher Silber, MD Sage Therapeutics
  Study Documents (Full-Text)

Documents provided by Sage Therapeutics:
Study Protocol  [PDF] January 13, 2017
Statistical Analysis Plan  [PDF] November 16, 2017

Additional Information:
Publications:
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Responsible Party: Sage Therapeutics
ClinicalTrials.gov Identifier: NCT03000530    
Other Study ID Numbers: 217-MDD-201
First Posted: December 22, 2016    Key Record Dates
Results First Posted: December 2, 2020
Last Update Posted: December 2, 2020
Last Verified: November 2020
Keywords provided by Sage Therapeutics:
Depression
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders