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.
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. This study was previously posted by Sage Therapeutics. In November 2023, sponsorship of the trial was transferred to Biogen.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
102
Sage Investigational Site
Garden Grove, California, United States
Sage Investigational Site
Orlando, Florida, United States
Sage Investigational Site
Atlanta, Georgia, United States
Sage Investigational Site
Lake Charles, Louisiana, United States
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) - Part A
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.
Time frame: Day 1 up to Day 21
Percentage of Participants With TEAEs, Graded by Severity - Part A
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.
Time frame: Day 1 up to Day 21
Change From Baseline in Basophils - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Basophils to Leukocytes Ratio [Percentage (%)] - Part A
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 (%).
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Sage Investigational Site
Berlin, New Jersey, United States
Sage Investigational Site
Dayton, Ohio, United States
Sage Investigational Site
Austin, Texas, United States
Sage Investigational Site
Charlottesville, Virginia, United States
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Eosinophils - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part A
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Hematocrit - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Hemoglobin - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Lymphocytes - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part A
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Monocytes - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part A
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Neutrophils - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part A
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Platelets - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Erythrocytes - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Reticulocytes - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Leukocytes - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Albumin - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Alkaline Phosphatase - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Alanine Aminotransferase - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Aspartate Aminotransferase - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Bilirubin - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Chloride - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Carbon Dioxide - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Creatinine - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Potassium - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Protein - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Sodium - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Urea Nitrogen - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Activated Partial Thromboplastin Time - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part A
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Prothrombin Time - Part A
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in pH - Part A
Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part A of the study. ET = Early Termination.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline in Specific Gravity - Part A
Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part A of the study. ET = Early Termination.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Day 21, follow-up Day 28
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part A
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.
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
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part A
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.
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
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part A
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.
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
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part A
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.
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
Change From Baseline (CFB) in Heart Rate - Part A
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.
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
Change From Baseline (CFB) in Respiratory Rate - Part A
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.
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
Change From Baseline (CFB) in Oral Temperature - Part A
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.
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
Change From Baseline (CFB) in Oxygen Saturation - Part A
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).
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)
Change From Baseline in QT Interval - Part A
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Change From Baseline in QTcF Interval - Part A
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Change From Baseline in ECG Mean Heart Rate - Part A
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Change From Baseline in RR Interval - Part A
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Change From Baseline in PR Interval - Part A
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Change From Baseline in QRS Interval - Part A
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Percentage of Participants With a Response of 'Yes' to Any Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item - Part A
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.
Time frame: Day 1 up to Day 28
Change From Baseline in Stanford Sleepiness Scale (SSS) Score at Day 15 - Part A
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.
Time frame: Baseline, Day 15
Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15 - Part B
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.
Time frame: Baseline, Day 15
Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A
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.
Time frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28
Percentage of Participants With TEAEs - Part B
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.
Time frame: Day 1 up to Day 21
Percentage of Participants With AEs During Post-TEAE Period
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.
Time frame: Day 21 up to Day 42
Percentage of Participants With TEAEs, Graded by Severity - Part B
Severity was assessed according to the following scale: mild (awareness of sign or symptom, but easily tolerated); moderate (discomfort sufficient to cause interference with normal activities); severe (incapacitating, with inability to perform normal activities). The analysis was performed in participants included in Part B of the study.
Time frame: Day 1 up to Day 21
Change From Baseline in Basophils - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Basophils to Leukocytes Ratio (%) - Part B
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Eosinophils - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Eosinophils to Leukocytes Ratio (%) - Part B
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Hematocrit - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Hemoglobin - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Lymphocytes - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Lymphocytes to Leukocytes Ratio (%) - Part B
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Monocytes - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Monocytes to Leukocytes Ratio (%) - Part B
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Neutrophils - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Neutrophils to Leukocytes Ratio (%) - Part B
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Platelets - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Erythrocytes - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Reticulocytes - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET
Change From Baseline in Reticulocytes to Erythrocytes Ratio (%) - Part B
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Leukocytes - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Albumin - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Alkaline Phosphatase - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Alanine Aminotransferase - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Aspartate Aminotransferase - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Bilirubin - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Calcium - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Chloride - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Carbon Dioxide - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Creatinine - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Glucose - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Potassium - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Magnesium - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Phosphate - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Protein - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Sodium - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Thyrotropin - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Urea Nitrogen - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Activated Partial Thromboplastin Time - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Prothrombin International Normalized Ratio (%) - Part B
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 (%).
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Prothrombin Time - Part B
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.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in pH - Part B
Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part B of the study. ET = Early Termination.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline in Specific Gravity - Part B
Urinalysis measures included pH and specific gravity. The analysis was performed in participants included in Part B of the study. ET = Early Termination.
Time frame: Baseline, Day 8, Day 15/ET, follow-up Days 21, 28, 35 and 42
Change From Baseline (CFB) in Supine Systolic Blood Pressure - Part B
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.
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
Change From Baseline (CFB) in Supine Diastolic Blood Pressure - Part B
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.
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
Change From Baseline (CFB) in Standing Systolic Blood Pressure - Part B
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.
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
Change From Baseline (CFB) in Standing Diastolic Blood Pressure - Part B
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.
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
Change From Baseline (CFB) in Heart Rate - Part B
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.
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
Change From Baseline (CFB) in Respiratory Rate - Part B
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.
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
Change From Baseline (CFB) in Oral Temperature - Part B
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.
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
Change From Baseline (CFB) in Oxygen Saturation - Part B
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.
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)
Change From Baseline in QT Interval - Part B
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Change From Baseline in QTcF Interval - Part B
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Change From Baseline in ECG Mean Heart Rate - Part B
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Change From Baseline in RR Interval - Part B
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Change From Baseline in PR Interval - Part B
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Change From Baseline in QRS Duration - Part B
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.
Time frame: Baseline, Days 1, 2, 7, 14 and follow-up Day 21
Percentage of Participants With a Response of "Yes" to Any C-SSRS Suicidal Ideation (SI) Item - Part B
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.
Time frame: Screening, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 21, 28, 35 and 42
Percentage of Participants With HAM-D Response - Part A
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.
Time frame: Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28
Percentage of Participants With HAM-D Remission - Part A
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.
Time frame: Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28
Change From Baseline in the Montgomery and Åsberg Depression Rating Scale (MADRS) Total Score at Day 15 and All Other Time Points - Part A
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.
Time frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28
Change From Baseline in HAM-D Subscale Scores at Day 15 and All Other Time Points - Part A
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.
Time frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28
Change From Baseline (CFB) in HAM-D Individual Item Scores at Day 15 and All Other Time Points - Part A
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.
Time frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21 and 28
Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at All Time Points - Part A
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.
Time frame: Baseline, Days 2, 3, 8, 15, 21 and 28
Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response - Part A
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.
Time frame: Days 2, 3, 8, 15, 21 and 28
Change From Baseline (CFB) in the SSS Score - Part B
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).
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
Change From Baseline in the 17-item HAM-D Total Score at All Time Points - Part B
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.
Time frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21, 28, 35 and 42
Percentage of Participants With HAM-D Response - Part B
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.
Time frame: Days 2, 8, 15, 21, 28, 35 and 42
Percentage of Participants With HAM-D Remission - Part B
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.
Time frame: Days 2, 8, 15, 21, 28, 35 and 42
Change From Baseline in the MADRS Total Score at Day 15 and All Other Time Points - Part B
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.
Time frame: Baseline, Days 2, 8, 15, 21, 28, 35 and 42
Change From Baseline in HAM-D Subscale Scores at All Time Points - Part B
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.
Time frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21, 28, 35 and 42
Change From Baseline (CFB) in HAM-D Individual Item Scores at All Time Points - Part B
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.
Time frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 15, 21, 28, 35 and 42
Change From Baseline in HAM-A Total Score at Day 15 and All Other Time Points - Part B
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.
Time frame: Baseline, Days 2, 8, 15, 21, 28, 35 and 42
Percentage of Participants With CGI-I Response - Part B
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.
Time frame: Days 2, 8, 15, 21, 28, 35 and 42