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

NCT03000530 | Completed Phase 2 Results

• 1 other identifier: 217-MDD-201
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 8

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.

Conditions

Major Depression

Keywords

Depression

Outcome Measures

Primary Outcomes (52)

• 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.

  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.

  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.

  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 (%).

  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.

  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 (%).

  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.

  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.

  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.

  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 (%).

  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.

  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 (%).

  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.

  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 (%).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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 (%).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Baseline, Day 15

Secondary Outcomes (74)

• Change From Baseline in the HAM-D Total Score at Day 15 and All Other Time Points - Part A

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

• Percentage of Participants With TEAEs - Part B

  Day 1 up to Day 21

• Percentage of Participants With AEs During Post-TEAE Period

  Day 21 up to Day 42

• Percentage of Participants With TEAEs, Graded by Severity - Part B

  Day 1 up to Day 21

• Change From Baseline in Basophils - Part B

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

Study Arms (3)

Part A: SAGE-217

EXPERIMENTAL

Participants received SAGE-217, 30 milligrams (mg), oral solution, once daily for 14 days, as tolerated.

Drug: SAGE-217

Part B: Placebo

PLACEBO COMPARATOR

Eligible participants received matching placebo capsules once daily for 14 days.

Drug: Placebo

Part B: SAGE-217

EXPERIMENTAL

Eligible participants received SAGE-217, 30 mg, oral capsules, once daily for 14 days.

Drug: SAGE-217

Interventions

SAGE-217 DRUG

Part A: SAGE-217; Part B: SAGE-217

Placebo DRUG

Part B: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Biogen: lead

Study Sites (8)

Sage Investigational Site

Garden Grove, California, 92845, United States

Location

Sage Investigational Site

Orlando, Florida, 32806, United States

Location

Sage Investigational Site

Atlanta, Georgia, 30331, United States

Location

Sage Investigational Site

Lake Charles, Louisiana, 70629, United States

Location

Sage Investigational Site

Berlin, New Jersey, 08009, United States

Location

Sage Investigational Site

Dayton, Ohio, 45417, United States

Location

Sage Investigational Site

Austin, Texas, 78754, United States

Location

Sage Investigational Site

Charlottesville, Virginia, 22908, United States

Location

Related Publications (2)

• Gunduz-Bruce H, Silber C, Kaul I, Rothschild AJ, Riesenberg R, Sankoh AJ, Li H, Lasser R, Zorumski CF, Rubinow DR, Paul SM, Jonas J, Doherty JJ, Kanes SJ. Trial of SAGE-217 in Patients with Major Depressive Disorder. N Engl J Med. 2019 Sep 5;381(10):903-911. doi: 10.1056/NEJMoa1815981.

  PMID: 31483961 BACKGROUND

• Suthoff E, Kosinski M, Arnaud A, Hodgkins P, Gunduz-Bruce H, Lasser R, Silber C, Sankoh AJ, Li H, Werneburg B, Jonas J, Doherty J, Kanes SJ, Bonthapally V. Patient-reported health-related quality of life from a randomized, placebo-controlled phase 2 trial of zuranolone in adults with major depressive disorder. J Affect Disord. 2022 Jul 1;308:19-26. doi: 10.1016/j.jad.2022.03.068. Epub 2022 Apr 2.

  PMID: 35378149 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

zuranolone

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2016
• First Posted: December 22, 2016
• Study Start: December 7, 2016
• Primary Completion: October 4, 2017
• Study Completion: November 8, 2017
• Last Updated: November 28, 2023
• Results First Posted: December 2, 2020

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share

Locations

US (8)