Major Depressive Disorder
Conditions
Brief summary
This is a Phase 2 clinical study evaluating the safety and effectiveness of SP-624 as compared to placebo in the treatment of adults with Major Depressive Disorder.
Interventions
DRUGSP-624
Oral capsule
DRUGPlacebo
Oral capsule
Sponsors
Sirtsei Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide written informed consent to participate in the study * Males and females, aged 18 to 65 years * In generally good physical health * Body mass index (BMI) must be between 18 and 40 kg/m2 * Females of reproductive potential and males with partners of reproductive potential must agree to remain abstinent or use adequate and reliable contraception throughout the study and for at least 30 days after the last dose of study drug * Subjects must meet criteria for moderate to severe Major Depressive Disorder, as confirmed by the Mini International Neuropsychiatric Interview (MINI) * Willing and able to comply with the study design schedule and other requirements
Exclusion criteria
* Female who is pregnant, breastfeeding, or less than six months postpartum at Screening * History or presence of any clinically significant medical condition, disease, or surgical history that could jeopardize the safety of the subject or validity of the study data, or interfere with the absorption, distribution, metabolism, or excretion of the study drug * Failure to discontinue all psychoactive medications or psychoactive supplements including antidepressants and mood stabilizers, within a time period prior to Baseline corresponding to at least five half-lives of the medication in question * Presence of a clinically significant abnormality on physical examination or electrocardiogram (ECG), including a corrected QT interval using Fridericia's formula (QTcF) \>450 msec for males and \>470 msec for females * Presence of uncontrolled hypertension, defined as consistent systolic blood pressure (SBP) \>160 mmHg or consistent diastolic blood pressure (DBP) \>95 mmHg despite present therapy * Screening laboratory value(s) outside the laboratory reference range that are considered to be clinically significant by the Investigator (clinical chemistry, hematology, coagulation, and urinalysis) * Screening liver function tests (ALT, AST, Alkaline phosphatase) \> 2x the upper limit of normal * Subjects who, in the opinion of the Investigator, are not suitable candidates for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 4 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | Baseline to Week 4 | The Montgomery Asberg Depression rating scale is a 10-item scale used to assess the severity of depression. Individual items are scored on a 7-point scale (0 to 6). The total score is the sum of individual items, ranging from 0 to 60; where a higher score indicates more depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 4 in Clinical Global Impression - Severity (CGI-S) Total Score | Baseline to Week 4 | The CGI-S is a 7-point 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. A score of 1 represents normal and 7 represents most extremely ill. |
| Change From Baseline to Week 4 in the 17-item Hamilton Depression Rating Scale (HAM D-17) Total Score | Baseline to Week 4 | The 17-item Hamilton Depression rating scale is used to assess the severity of depression. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=No difficulty/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression. |
| Change From Baseline to Week 4 in the Sheehan Disability Scale (SDS) | Baseline to Week 4 | The Sheehan Disability Scale is a 3-part scale that measures the degree of disruption on work, social, and family life using an 11-point scale where 0 represents no disruption and 10 represents extreme disruption. Each item (work, social, and family life) can have a score of 0-10. A total global functioning impairment score can be utilized by summing the scores from work, social, and family life scales for a value range from 0 to 30, where a higher score represents a worse outcome, i.e., more disruption on work, social, and family life. In addition to the 11-point scale, participants are asked to indicate the number of days in the past week that were lost and numbers of days that were unproductive. The results of these questions have a range from 0 to 7 and are not included in the overall scale total. |
| Change From Baseline to Week 4 in the Quick Inventory of Depressive Symptomology - Self Report (QIDS-SR) | Baseline to Week 4 | The Quick Inventory of Depressive Symptomology - Self Report (QIDS-SR), is a 16 item self-reported scale where each item has a 4-point scale where 0 represents least impact scores while 3 represents greatest impact scores. Some questions are linked such that the highest score in a group of questions is entered once. For example, there are 4 questions related to sleep and the highest score on any of the 4 sleep items is entered once. The total score ranges from 0 to 27 where a higher score indicates more depression. |
| Change From Baseline to Week 4 in the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) | Baseline to Week 4 | The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 16 item satisfaction scale where each item has a 5-point scale. A score of 1 represents very poor satisfaction, while a score of 5 represents very good satisfaction. Only the first 14 items are summed for a total score that ranges from 14 to 70, where a lower score represents a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SP-624 Daily oral capsule, 20 mg/day
SP-624: Oral capsule | 161 |
| Placebo Daily oral capsule
Placebo: Oral capsule | 156 |
| Total | 317 |
Baseline characteristics
| Characteristic | SP-624 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 156 Participants | 154 Participants | 310 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 21 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 142 Participants | 135 Participants | 277 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 10 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 39 Participants | 32 Participants | 71 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 108 Participants | 107 Participants | 215 Participants |
| Region of Enrollment United States | 161 Participants | 156 Participants | 317 Participants |
| Sex: Female, Male Female | 101 Participants | 110 Participants | 211 Participants |
| Sex: Female, Male Male | 60 Participants | 46 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 161 | 0 / 156 |
| other Total, other adverse events | 35 / 161 | 36 / 156 |
| serious Total, serious adverse events | 0 / 161 | 2 / 156 |
Outcome results
Primary
Change From Baseline to Week 4 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score
The Montgomery Asberg Depression rating scale is a 10-item scale used to assess the severity of depression. Individual items are scored on a 7-point scale (0 to 6). The total score is the sum of individual items, ranging from 0 to 60; where a higher score indicates more depression.
Time frame: Baseline to Week 4
Population: Modified Intent To Treat population - all subjects who are randomized to receive treatment, receive at least one dose of study drug, and have a Baseline and at least one post-dose efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SP-624 | Change From Baseline to Week 4 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | -12.6 Score on a scale | Standard Error 0.83 |
| Placebo | Change From Baseline to Week 4 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | -10.8 Score on a scale | Standard Error 0.84 |
p-value: 0.13395% CI: [-4.1, 0.5]Mixed Models Analysis
Secondary
Change From Baseline to Week 4 in Clinical Global Impression - Severity (CGI-S) Total Score
The CGI-S is a 7-point 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. A score of 1 represents normal and 7 represents most extremely ill.
Time frame: Baseline to Week 4
Population: Modified Intent To Treat population - all subjects who are randomized to receive treatment, receive at least one dose of study drug, and have a Baseline and at least one post-dose efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SP-624 | Change From Baseline to Week 4 in Clinical Global Impression - Severity (CGI-S) Total Score | -1.2 Score on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline to Week 4 in Clinical Global Impression - Severity (CGI-S) Total Score | -0.9 Score on a scale | Standard Error 0.1 |
p-value: 0.05995% CI: [-0.5, 0]Mixed Models Analysis
Secondary
Change From Baseline to Week 4 in the 17-item Hamilton Depression Rating Scale (HAM D-17) Total Score
The 17-item Hamilton Depression rating scale is used to assess the severity of depression. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=No difficulty/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.
Time frame: Baseline to Week 4
Population: Modified Intent To Treat population - all subjects who are randomized to receive treatment, receive at least one dose of study drug, and have a Baseline and at least one post-dose efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SP-624 | Change From Baseline to Week 4 in the 17-item Hamilton Depression Rating Scale (HAM D-17) Total Score | -8.3 Score on a scale | Standard Error 0.56 |
| Placebo | Change From Baseline to Week 4 in the 17-item Hamilton Depression Rating Scale (HAM D-17) Total Score | -7.1 Score on a scale | Standard Error 0.57 |
p-value: 0.15995% CI: [-2.7, 0.4]Mixed Models Analysis
Secondary
Change From Baseline to Week 4 in the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF)
The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 16 item satisfaction scale where each item has a 5-point scale. A score of 1 represents very poor satisfaction, while a score of 5 represents very good satisfaction. Only the first 14 items are summed for a total score that ranges from 14 to 70, where a lower score represents a worse outcome.
Time frame: Baseline to Week 4
Population: Modified Intent To Treat population - all subjects who are randomized to receive treatment, receive at least one dose of study drug, and have a Baseline and at least one post-dose efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SP-624 | Change From Baseline to Week 4 in the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) | 9.5 Score on a scale | Standard Error 1.03 |
| Placebo | Change From Baseline to Week 4 in the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) | 7.8 Score on a scale | Standard Error 1.06 |
p-value: 0.24395% CI: [-1.2, 4.6]Mixed Models Analysis
Secondary
Change From Baseline to Week 4 in the Quick Inventory of Depressive Symptomology - Self Report (QIDS-SR)
The Quick Inventory of Depressive Symptomology - Self Report (QIDS-SR), is a 16 item self-reported scale where each item has a 4-point scale where 0 represents least impact scores while 3 represents greatest impact scores. Some questions are linked such that the highest score in a group of questions is entered once. For example, there are 4 questions related to sleep and the highest score on any of the 4 sleep items is entered once. The total score ranges from 0 to 27 where a higher score indicates more depression.
Time frame: Baseline to Week 4
Population: Modified Intent To Treat population - all subjects who are randomized to receive treatment, receive at least one dose of study drug, and have a Baseline and at least one post-dose efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SP-624 | Change From Baseline to Week 4 in the Quick Inventory of Depressive Symptomology - Self Report (QIDS-SR) | -5.0 Score on a scale | Standard Error 0.39 |
| Placebo | Change From Baseline to Week 4 in the Quick Inventory of Depressive Symptomology - Self Report (QIDS-SR) | -4.1 Score on a scale | Standard Error 0.4 |
p-value: 0.09195% CI: [-2, 0.2]Mixed Models Analysis
Secondary
Change From Baseline to Week 4 in the Sheehan Disability Scale (SDS)
The Sheehan Disability Scale is a 3-part scale that measures the degree of disruption on work, social, and family life using an 11-point scale where 0 represents no disruption and 10 represents extreme disruption. Each item (work, social, and family life) can have a score of 0-10. A total global functioning impairment score can be utilized by summing the scores from work, social, and family life scales for a value range from 0 to 30, where a higher score represents a worse outcome, i.e., more disruption on work, social, and family life. In addition to the 11-point scale, participants are asked to indicate the number of days in the past week that were lost and numbers of days that were unproductive. The results of these questions have a range from 0 to 7 and are not included in the overall scale total.
Time frame: Baseline to Week 4
Population: Modified Intent To Treat population - all subjects who are randomized to receive treatment, receive at least one dose of study drug, and have a Baseline and at least one post-dose efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SP-624 | Change From Baseline to Week 4 in the Sheehan Disability Scale (SDS) | -5.6 Score on a scale | Standard Error 0.52 |
| Placebo | Change From Baseline to Week 4 in the Sheehan Disability Scale (SDS) | -4.6 Score on a scale | Standard Error 0.54 |
p-value: 0.18895% CI: [-2.5, 0.5]Mixed Models Analysis
Post Hoc
Female Change From Baseline to Week 4 in Clinical Global Impression - Severity (CGI-S) Total Score
The CGI-S is a 7-point 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. A score of 1 represents normal and 7 represents most extremely ill.
Time frame: Baseline to Week 4
Population: Modified Intent To Treat population - all subjects who are randomized to receive treatment, receive at least one dose of study drug, and have a Baseline and at least one post-dose efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SP-624 | Female Change From Baseline to Week 4 in Clinical Global Impression - Severity (CGI-S) Total Score | -1.2 Score on a scale | Standard Error 0.12 |
| Placebo | Female Change From Baseline to Week 4 in Clinical Global Impression - Severity (CGI-S) Total Score | -0.8 Score on a scale | Standard Error 0.11 |
p-value: 0.00695% CI: [-0.8, -0.1]Mixed Models Analysis
Post Hoc
Female Subjects Change From Baseline Montgomery Asberg Depression Rating Scale Score at Week 4
The Montgomery Asberg Depression rating scale is a 10-item scale used to assess the severity of depression. Individual items are scored on a 7-point scale (0 to 6). The total score is the sum of individual items, ranging from 0 to 60; where a higher score indicates more depression.
Time frame: Baseline to Week 4
Population: Modified Intent To Treat population - all subjects who are randomized to receive treatment, receive at least one dose of study drug, and have a Baseline and at least one post-dose efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SP-624 | Female Subjects Change From Baseline Montgomery Asberg Depression Rating Scale Score at Week 4 | -13.4 Score on a scale | Standard Error 1.05 |
| Placebo | Female Subjects Change From Baseline Montgomery Asberg Depression Rating Scale Score at Week 4 | -9.4 Score on a scale | Standard Error 1.02 |
p-value: 0.00895% CI: [-6.8, -1]Mixed Models Analysis
Post Hoc
Male Change From Baseline to Week 4 in Clinical Global Impression - Severity (CGI-S) Total Score
The CGI-S is a 7-point 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. A score of 1 represents normal and 7 represents most extremely ill.
Time frame: Baseline to Week 4
Population: Modified Intent To Treat population - all subjects who are randomized to receive treatment, receive at least one dose of study drug, and have a Baseline and at least one post-dose efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SP-624 | Male Change From Baseline to Week 4 in Clinical Global Impression - Severity (CGI-S) Total Score | -1.0 Score on a scale | Standard Error 0.15 |
| Placebo | Male Change From Baseline to Week 4 in Clinical Global Impression - Severity (CGI-S) Total Score | -1.2 Score on a scale | Standard Error 0.16 |
p-value: 0.43795% CI: [-0.3, 0.6]Mixed Models Analysis
Post Hoc
Male Subjects Change From Baseline Montgomery Asberg Depression Rating Scale Score at Week 4
The Montgomery Asberg Depression rating scale is a 10-item scale used to assess the severity of depression. Individual items are scored on a 7-point scale (0 to 6). The total score is the sum of individual items, ranging from 0 to 60; where a higher score indicates more depression.
Time frame: Baseline to Week 4
Population: Modified Intent To Treat population - all subjects who are randomized to receive treatment, receive at least one dose of study drug, and have a Baseline and at least one post-dose efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SP-624 | Male Subjects Change From Baseline Montgomery Asberg Depression Rating Scale Score at Week 4 | -11.3 Score on a scale | Standard Error 1.21 |
| Placebo | Male Subjects Change From Baseline Montgomery Asberg Depression Rating Scale Score at Week 4 | -14.0 Score on a scale | Standard Error 1.35 |
p-value: 0.13495% CI: [-0.8, 6.3]Mixed Models Analysis