Trial Outcomes & Findings for A Study to Evaluate SAGE-217 in Participants With Bipolar I/II Disorder With a Current Major Depressive Episode (NCT NCT03692910)
NCT ID: NCT03692910
Last Updated: 2023-12-13
Results Overview
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 (including an abnormal laboratory finding), 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 adverse event with onset after the start of study through Day 42/early termination.
COMPLETED
PHASE2
35 participants
From first dose of study drug up to Day 42
2023-12-13
Participant Flow
Participants took part in the study at 11 investigative sites in the United States from 23 August 2018 to 21 May 2019.
The study was to be conducted in 2 parts: Part A (Open-label) and Part B (Double-blind). Participants received SAGE-217 during the treatment period in Part A. Part B was to be initiated post review of Part A data. However, as per the Sponsor's decision, Part B was not conducted and hence no participants were enrolled in it and no data collection and analysis was done.
Participant milestones
| Measure |
Part A (Open-label): SAGE-217
Participants self-administered SAGE-217, 30 milligrams (mg), oral capsule, once daily (QD), in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): SAGE-217
Participants were to receive SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|---|
|
Overall Study
STARTED
|
35
|
0
|
0
|
|
Overall Study
COMPLETED
|
29
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
0
|
0
|
Reasons for withdrawal
| Measure |
Part A (Open-label): SAGE-217
Participants self-administered SAGE-217, 30 milligrams (mg), oral capsule, once daily (QD), in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): SAGE-217
Participants were to receive SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
4
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
0
|
Baseline Characteristics
A Study to Evaluate SAGE-217 in Participants With Bipolar I/II Disorder With a Current Major Depressive Episode
Baseline characteristics by cohort
| Measure |
Part A (Open-label): SAGE-217
n=35 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
|---|---|
|
Age, Continuous
|
47.6 years
STANDARD_DEVIATION 9.69 • n=93 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
18 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: From first dose of study drug up to Day 42Population: Safety Set included all participants who received at least one dose of study drug.
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 (including an abnormal laboratory finding), 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 adverse event with onset after the start of study through Day 42/early termination.
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=35 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs)
|
16 Participants
|
—
|
PRIMARY outcome
Timeframe: From first dose of study drug up to Day 42Population: Safety Set included all participants who received at least one dose of study drug.
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 (including an abnormal laboratory finding), 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 adverse event with onset after the start of study through Day 42/early termination. 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).
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=35 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Number of Participants With TEAEs, Graded by Severity
Mild
|
11 Participants
|
—
|
|
Part A: Number of Participants With TEAEs, Graded by Severity
Moderate
|
5 Participants
|
—
|
|
Part A: Number of Participants With TEAEs, Graded by Severity
Severe
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Baseline, Post-baseline (any time up to Day 42)Population: Safety Set included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available for analyses at the specific time point.
Suicidality was monitored using the C-SSRS. This scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicidal ideation and behavior, and a post-baseline evaluation that focuses on suicidality since the last study visit. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal), completed suicide). Percentage of participants with response 'yes' are reported for both suicidal ideation and behavior.
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=35 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Percentages of Participants With Response to Suicidal Ideation and Suicidal Behavior Based on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Suicidal Ideation: Baseline
|
22.9 percentage of participants
|
—
|
|
Part A: Percentages of Participants With Response to Suicidal Ideation and Suicidal Behavior Based on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Suicidal Ideation: Post-Baseline (Any Time up to Day 42)
|
9.4 percentage of participants
|
—
|
|
Part A: Percentages of Participants With Response to Suicidal Ideation and Suicidal Behavior Based on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Suicidal Behavior: Baseline
|
0 percentage of participants
|
—
|
|
Part A: Percentages of Participants With Response to Suicidal Ideation and Suicidal Behavior Based on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Suicidal Behavior: Post-Baseline (Any Time up to Day 42)
|
0 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: Baseline, Days 3, 8, 12, 15, 21, 28, 35, and 42, Last value on treatment (up to Day 14), Last value on study (up to Day 42)Population: Safety Set included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available for analyses at the specific time point.
Manic symptoms were assessed during the study using the YMRS. The clinician-administered scale is based on 11 items of core symptoms of mania. Four of the items (irritability, speech, thought content, and disruptive/aggressive behavior) were graded on a scale of 0 to 8 (choices given as even numbers), with the remaining 7 items graded on a scale of 0 to 4. Scoring between the points given (whole or half points) is possible. The YMRS total score ranges from 0 (no symptoms) to 60 (extreme severity of symptoms). A higher total score indicates a greater degree of mania. A negative change indicates better state of health.
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=35 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Change at Last Value on Treatment (up to Day 14)
|
-0.2 score on a scale
Standard Deviation 3.28
|
—
|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Baseline
|
4.9 score on a scale
Standard Deviation 3.23
|
—
|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Change From Baseline at Day 3
|
-0.9 score on a scale
Standard Deviation 2.24
|
—
|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Change From Baseline at Day 8
|
-0.9 score on a scale
Standard Deviation 2.66
|
—
|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Change From Baseline at Day 12
|
-0.7 score on a scale
Standard Deviation 3.35
|
—
|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Change From Baseline at Day 15
|
0.3 score on a scale
Standard Deviation 3.10
|
—
|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Change From Baseline at Day 21
|
-0.7 score on a scale
Standard Deviation 3.08
|
—
|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Change From Baseline at Day 28
|
-0.9 score on a scale
Standard Deviation 2.92
|
—
|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Change From Baseline at Day 35
|
-0.9 score on a scale
Standard Deviation 3.29
|
—
|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Change From Baseline at Day 42
|
-1.3 score on a scale
Standard Deviation 2.85
|
—
|
|
Part A: Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score
Change at Last Value on Study (up to Day 42)
|
-1.2 score on a scale
Standard Deviation 3.02
|
—
|
PRIMARY outcome
Timeframe: Baseline up to Day 42Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
The 17-item HAM-D was used to rate the severity of depression in participants who were identified as experiencing a major depressive episode (MDE). Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 include: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score was calculated as the sum of the 17 individual item scores, with a range of 0 (not at all depressed) to 52 (severely depressed). Higher scores indicated more depression. A negative change from baseline indicates improvement.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Day 15Population: Efficacy Set included all participants that received at least 1 dose of study drug, and who had at least one post-baseline Hamilton Depression Rating Scale (HAM-D) evaluation. Number analyzed is the number of participants with data available for analyses at the specific time point.
The 17-item HAM-D was used to rate the severity of depression in participants who were identified as experiencing an MDE. Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 include: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score was calculated as the sum of the 17 individual item scores, with a range of 0 (not at all depressed) to 52 (severely depressed). Higher scores indicated more depression. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=32 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Change From Baseline in the 17-Item HAM-D Total Score at Day 15
Baseline
|
25.7 score on a scale
Standard Deviation 2.97
|
—
|
|
Part A: Change From Baseline in the 17-Item HAM-D Total Score at Day 15
Day 15
|
-11.4 score on a scale
Standard Deviation 8.69
|
—
|
SECONDARY outcome
Timeframe: Day 15Population: Efficacy Set included all participants that received at least 1 dose of study drug, and who had at least one post-baseline Hamilton Depression Rating Scale (HAM-D) evaluation. Overall number of participants analyzed were the participants with data available for analyses.
HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. The HAM-D total score was calculated as the sum of the 17 individual item scores. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D total score was calculated as the sum of the 17 individual item scores, with a range of 0 (not at all depressed) to 52 (severely depressed). Higher scores indicated more depression.
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=23 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Percentage of Participants With HAM-D Response at Day 15
|
43.5 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Day 15Population: Efficacy Set included all participants that received at least 1 dose of study drug, and who had at least one post-baseline Hamilton Depression Rating Scale (HAM-D) evaluation. Overall number of participants analyzed were the participants with data available for analyses.
HAM-D remission was defined as having a HAM-D total score of ≤7. The HAM-D total score was calculated as the sum of the 17 individual item scores. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D total score was calculated as the sum of the 17 individual item scores, with a range of 0 (not at all depressed) to 52 (severely depressed). Higher scores indicated more depression.
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=23 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Percentage of Participants With HAM-D Remission at Day 15
|
30.4 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 15Population: Efficacy Set included all participants that received at least 1 dose of study drug, and who had at least one post-baseline Hamilton Depression Rating Scale (HAM-D) evaluation. Number analyzed is the number of participants with data available for analyses at the specific time point.
The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. It includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; and suicidal thoughts. Each item was scored in a range of 0 (no symptoms) to 6 (symptoms of maximum severity). The MADRS total score was calculated as the sum of the ten individual item scores and ranges from 0 (symptoms absent) to 60 (severe depression). Higher MADRS scores indicate more severe depression. A negative change indicates improvement.
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=32 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Day 15
Baseline
|
34.4 score on a scale
Standard Deviation 4.58
|
—
|
|
Part A: Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Day 15
Change From Baseline at Day 15
|
-15.5 score on a scale
Standard Deviation 11.67
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 15Population: Efficacy Set included all participants that received at least 1 dose of study drug, and who had at least one post-baseline Hamilton Depression Rating Scale (HAM-D) evaluation. Number analyzed is the number of participants with data available for analyses at the specific time 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 had the same diagnosis. Considering total clinical experience, a participant was assessed 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 negative change from baseline indicates improvement (higher absolute number indicating more illness).
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=32 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Change From Baseline in Response to the Clinical Global Impression - Severity (CGI-S) at Day 15
Baseline
|
4.4 score on a scale
Standard Deviation 0.62
|
—
|
|
Part A: Change From Baseline in Response to the Clinical Global Impression - Severity (CGI-S) at Day 15
Change From Baseline at Day 15
|
-1.4 score on a scale
Standard Deviation 1.24
|
—
|
SECONDARY outcome
Timeframe: Day 15Population: Efficacy Set included all participants that received at least 1 dose of study drug, and who had at least one post-baseline Hamilton Depression Rating Scale (HAM-D) evaluation. Overall number of participants analyzed were the participants with data available for analyses.
The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. Response choices included: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. Higher number indicating more illness. The CGI-I is only rated at posttreatment assessments. CGI-I response were defined as having a CGI-I score "very much improved" or "much improved."
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=23 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Percentage of Participants With Response to Clinical Global Impression - Improvement (CGI-I) at Day 15
|
47.8 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Day 15Population: Efficacy Set included all participants that received at least 1 dose of study drug, and who had at least one post-baseline Hamilton Depression Rating Scale (HAM-D) evaluation. Overall number of participants analyzed were the participants with data available for analyses.
The ISI is a validated questionnaire designed to assess the nature, severity, and impact of insomnia. The ISI uses a 5-point Likert Scale to measure various aspects of insomnia severity (0 = none, 1 = mild, 2 = moderate; 3 = severe; 4 = very severe), satisfaction with current sleep pattern (0 = very satisfied, 1 = satisfied, 2 = neutral, 3 = dissatisfied, 4 = very dissatisfied), and various aspects of the impact of insomnia on daily functioning (0 = not at all, 1 = a little, 2 = somewhat, 3 = much, 4 = very much). ISI total score ranges from 0 to 28, where a total score of 0 to 7 = no clinically significant insomnia, 8 to 14 = subthreshold insomnia, 15 to 21 = clinical insomnia (moderate severity), and 22 to 28 = clinical insomnia (severe). A lower value indicates better outcome.
Outcome measures
| Measure |
Part A (Open-label): SAGE-217
n=22 Participants
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
Part B (Double-blind): Placebo
Participants were to receive SAGE-217 matching placebo capsule, orally, QD, in the evening, from Day 1 to Day 14 in Part B of the study. However, as per the Sponsor's decision, the Part B of the study was not conducted.
|
|---|---|---|
|
Part A: Insomnia Severity Index (ISI) at Day 15
|
13.1 score on a scale
Standard Deviation 6.97
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 15Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
The 17-item HAM-D was used to rate the severity of depression in participants who were identified as experiencing an MDE. Items scored in a range of 0 to 2 include: insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items scored in a range of 0 to 4 include: agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), hypochondriasis. The HAM-D total score was calculated as the sum of the 17 individual item scores, with a total score of 0 (not at all depressed) to 52 (severely depressed). Higher scores indicated more depression. A negative change from baseline indicates improvement.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 15Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
HAM-D response was defined as having a 50% or greater reduction from baseline in HAM-D total score. The HAM-D total score was calculated as the sum of the 17 individual item scores. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D total score was calculated as the sum of the 17 individual item scores, with a range of 0 (not at all depressed) to 52 (severely depressed). Higher scores indicated more depression.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 15Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
HAM-D remission was defined as having a HAM-D total score of ≤7. The HAM-D total score was calculated as the sum of the 17 individual item scores. The 17-item HAM-D comprises individual ratings related to the following symptoms: depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D total score was calculated as the sum of the 17 individual item scores, with a range of 0 (not at all depressed) to 52 (severely depressed). Higher scores indicated more depression.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Day 15Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. It includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; and suicidal thoughts. Each item was scored in a range of 0 (no symptoms) to 6 (symptoms of maximum severity). The MADRS total score was calculated as the sum of the ten individual item scores and ranges from 0 (symptoms absent) to 60 (severe depression). Higher MADRS scores indicate more severe depression. A negative change indicates improvement.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Day 15Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
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 had the same diagnosis. Considering total clinical experience, a participant was assessed 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 negative change from baseline indicates improvement (higher absolute number indicating more illness).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 15Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
The CGI-I employs a 7-point Likert scale to measure the overall improvement in the participant's condition posttreatment. The Investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. Response choices included: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. Higher number indicating more illness. The CGI-I is only rated at posttreatment assessments. CGI-I response were defined as having a CGI-I score "very much improved" or "much improved."
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From first dose of study drug up to Day 42Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
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 (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as an adverse event with onset after the start of study through Day 42/early termination.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From first dose of study drug up to Day 42Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
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 (including an abnormal laboratory finding), 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 adverse event with onset after the start of study through Day 42/early termination. 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).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to Day 42Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
Suicidality was monitored using the C-SSRS. This scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicidal ideation and behavior, and a post-baseline evaluation that focuses on suicidality since the last study visit. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal), completed suicide). Percentage of participants with response 'yes' were to be reported for both suicidal ideation and behavior.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to Day 42Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
Manic symptoms were assessed during the study using the YMRS. The clinician-administered scale is based on 11 items of core symptoms of mania. Four of the items (irritability, speech, thought content, and disruptive/aggressive behavior) were graded on a scale of 0 to 8 (choices given as even numbers), with the remaining 7 items graded on a scale of 0 to 4. Scoring between the points given (whole or half points) is possible. The YMRS total score ranges from 0 (no symptoms) to 60 (extreme severity of symptoms). A higher total score indicates a greater degree of mania. A negative change indicates better state of health.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 15Population: Part B of the study was not conducted, so data was not collected and analyzed for this outcome measure.
The ISI is a validated questionnaire designed to assess the nature, severity, and impact of insomnia. The ISI uses a 5-point Likert Scale to measure various aspects of insomnia severity (0 = none, 1 = mild, 2 = moderate; 3 = severe; 4 = very severe), satisfaction with current sleep pattern (0 = very satisfied, 1 = satisfied, 2 = neutral, 3 = dissatisfied, 4 = very dissatisfied), and various aspects of the impact of insomnia on daily functioning (0 = not at all, 1 = a little, 2 = somewhat, 3 = much, 4 = very much). ISI total score ranges from 0 to 28, where a total score of 0 to 7 = no clinically significant insomnia, 8 to 14 = subthreshold insomnia, 15 to 21 = clinical insomnia (moderate severity), and 22 to 28 = clinical insomnia (severe). A lower value indicates better outcome.
Outcome measures
Outcome data not reported
Adverse Events
Part A (Open-label): SAGE-217
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part A (Open-label): SAGE-217
n=35 participants at risk
Participants self-administered SAGE-217, 30 mg, oral capsule, QD, in the evening, from Day 1 to Day 14.
|
|---|---|
|
Nervous system disorders
Somnolence
|
11.4%
4/35 • From first dose of study drug up to Day 42
Safety Set included all participants who received at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
8.6%
3/35 • From first dose of study drug up to Day 42
Safety Set included all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
5.7%
2/35 • From first dose of study drug up to Day 42
Safety Set included all participants who received at least one dose of study drug.
|
|
Psychiatric disorders
Hypomania
|
5.7%
2/35 • From first dose of study drug up to Day 42
Safety Set included all participants who received at least one dose of study drug.
|
|
Nervous system disorders
Sedation
|
5.7%
2/35 • From first dose of study drug up to Day 42
Safety Set included all participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
- Publication restrictions are in place
Restriction type: OTHER