A Comparative Study of Sage-217 Plus an Antidepressant (ADT) Versus Placebo Plus an ADT in Adults With Major Depressive Disorder

The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. A negative change from baseline indicated improvement. Least Squares (LS) mean was estimated using mixed effects model for repeated measures (MMRM) analysis.

The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. A negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis. The data reported is summary of data collected and analyzed during double-blind treatment period at Baseline, Day 3, Day 8, Day 12, and Day 15 using equal weights for the scheduled visits.

The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. A negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis. The missing values were imputed for the analysis.

The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. A negative change from baseline indicated improvement. End of blinded treatment was defined as the average of change from baseline values of Days 12, 15 and 18. LS mean was estimated using MMRM analysis.

HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. Percentages were rounded off to the first decimal point.

HAM-D remission was defined as having a HAM-D total score of ≤7. The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. Percentages were rounded off to the first decimal point.

The CGI-S uses a 7-point Likert scale to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. Considering total clinical experience, the investigator rated the participant on severity of mental illness at the time of rating as: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = extremely ill. A higher score indicated extreme illness. A negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis.

CGI-I response was defined as having a CGI-I score of "very much improved" or "much improved." The CGI-I employs 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 IP. 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. By definition, all CGI-I assessments are evaluated against baseline conditions. Higher scores indicated worse condition. Percentages were rounded off to the first decimal point.

The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. The MADRS total score was calculated as the sum of the 10 individual item scores. Each item yields a score of 0 (no symptoms) to 6 (symptoms of maximum severity). The total MADRS score (sum of all individual items) ranges from 0 (symptoms absent) to 60 (severe depression). Higher MADRS scores indicated more severe depression. A negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis.

MADRS response was defined as having a 50% or greater reduction from baseline in MADRS total score. The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. The MADRS total score was calculated as the sum of the 10 individual item scores. Each item yields a score of 0 (no symptoms) to 6 (symptoms of maximum severity). The total MADRS score (sum of all individual items) ranges from 0 (symptoms absent) to 60 (severe depression). Higher MADRS scores indicated more severe depression. Percentages were rounded off to the first decimal point.

MADRS remission was defined as having a MADRS total score of ≤10. The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. The MADRS total score was calculated as the sum of the 10 individual item scores. Each item yields a score of 0 (no symptoms) to 6 (symptoms of maximum severity). The total MADRS score (sum of all individual items) ranges from 0 (symptoms absent) to 60 (severe depression). Higher MADRS scores indicated more severe depression. Percentages were rounded off to the first decimal point.

Each of the 14 items in the HAM-A was defined by a series of symptoms, and measured both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints). The HAM-A total score was calculated as sum of the 14 individual item scores, each rated on a five point scale ranging from 0 (not present) to 4 (very severe). The total score (sum of all individual items) range from 0 to 56, where <17 indicated mild severity, 18 to 24 indicated mild to moderate severity, and 25 to 30 indicated moderate to severe severity. Higher scores indicated more severe disease. Negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis.

HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either 3-point (0=none to 2=severe) or 5-point scale (0=none/absent to 4=most severe). Total score is the sum of individual items, ranging from 0 (not depressed) to 52 (severely depressed); where a higher score indicates more depression. Time (in days) from first dose of study drug to time of first HAMD response was reported in this outcome measure.

The PHQ-9 is a participant-rated depressive symptom severity scale. The PHQ-9 total score is calculated as the sum of the 9 individual item scores. For individual items, scoring is based on responses to specific questions, as follows: 0 = not at all; 1 = several days; 2 = more than half the days; and 3 = nearly every day. The PHQ-9 possible total score range is 0 to 27, with higher scores reflecting greater depressive symptoms, and is categorized as follows: 0 to 4 = minimal depression, 5 to 9 = mild depression, 10 to 14 = moderate depression, 15 to 19 = moderately severe depression, and 20 to 27 = severe depression. Negative change from baseline indicated improvement. LS mean was estimated using MMRM analysis.

An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE was defined as an AE with onset after the start of IP, or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.

An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE was defined as an AE with onset after the start of IP, or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. The severity was graded as mild, moderate and severe.