Bipolar Depression, Major Depressive Disorder
Conditions
Keywords
Mixed Features
Brief summary
This is a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of lumateperone monotherapy in the treatment of patients with major depressive episodes associated with Bipolar I or Bipolar II Disorder (Bipolar Depression) or major depressive disorder (MDD) who also meet the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5) criteria for mixed-features. The study consists of a Screening Period, a Double-blind Treatment Period, and a Safety Follow-up Period.
Interventions
DRUGLumateperone
Lumateperone 42mg oral capsule
DRUGPlacebos
Placebo oral capsule
Sponsors
Intra-Cellular Therapies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: * Male or female subjects of any race, ages 18-75 inclusive * Meets the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM 5) criteria for Bipolar I or Bipolar II Disorder or MDD * The start of the current major depressive episode is at least 2 weeks but no more than 6 months prior to the Screening (Visit 1) * Has at least moderate severity of illness, as measured by a rater-administered MADRS total score ≥ 24 and corresponding to a CGI S score of ≥ 4 at Screening (Visit 1) and Baseline (Visit 2) * The patient meets the DSM-5 criteria for mixed-features specific to the Bipolar I or II diagnosis or MDD diagnosis * Current major depressive episode is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning * Able to provide written informed consent Major
Exclusion criteria
* Any female subject who is pregnant or breast-feeding * Any subject judged to be medically inappropriate for study participation * The patient has a significant risk for suicidal behavior * The patient presents with a lifetime history of epilepsy, seizure or convulsion, or electroencephalogram with clinically significant abnormalities, delirium, dementia, amnestic, or other cognitive disorder or significant brain trauma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | Day 43 | The Montgomery-Åsberg Depression Rating Scale is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) | Day 43 | The Clinical Global Impression Scale-Severity is a clinician-rated scale to assess a patient's overall mental health. The scale ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). |
Countries
Bulgaria, Russia, Serbia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lumateperone 42mg Lumateperone 42mg administered once daily in the evening
Lumateperone: Lumateperone 42mg oral capsule | 240 |
| Placebo Matching placebo administered once daily in the evening
Placebos: Placebo oral capsule | 241 |
| Total | 481 |
Baseline characteristics
| Characteristic | Total | Placebo | Lumateperone 42mg |
|---|---|---|---|
| Age, Continuous | 43.2 years STANDARD_DEVIATION 14.21 | 43.4 years STANDARD_DEVIATION 13.89 | 42.9 years STANDARD_DEVIATION 14.54 |
| Montgomery-Asberg Depression Rating Scale Bipolar Depression Mixed Features Population | 31.5 units on a scale STANDARD_DEVIATION 4.22 | 31.1 units on a scale STANDARD_DEVIATION 4.01 | 31.8 units on a scale STANDARD_DEVIATION 4.4 |
| Montgomery-Asberg Depression Rating Scale Combined MDD and Bipolar Depression Mixed Features Population | 31.3 units on a scale STANDARD_DEVIATION 4.06 | 31.1 units on a scale STANDARD_DEVIATION 4.07 | 31.3 units on a scale STANDARD_DEVIATION 4.05 |
| Montgomery-Asberg Depression Rating Scale MDD Mixed Features Population | 31.0 units on a scale STANDARD_DEVIATION 3.88 | 31.2 units on a scale STANDARD_DEVIATION 4.16 | 30.8 units on a scale STANDARD_DEVIATION 3.59 |
| Montgomery-Asberg Depression Rating Scale Overall Population | 31.3 units on a scale STANDARD_DEVIATION 4.34 | 31.4 units on a scale STANDARD_DEVIATION 4.36 | 31.3 units on a scale STANDARD_DEVIATION 4.33 |
| Race/Ethnicity, Customized Race Asian | 3 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black or African American | 81 Participants | 49 Participants | 32 Participants |
| Race/Ethnicity, Customized Race Multiple | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 393 Participants | 188 Participants | 205 Participants |
| Region of Enrollment Bulgaria | 167 participants | 92 participants | 75 participants |
| Region of Enrollment Russia | 78 participants | 30 participants | 48 participants |
| Region of Enrollment Serbia | 39 participants | 24 participants | 15 participants |
| Region of Enrollment Ukraine | 37 participants | 17 participants | 20 participants |
| Region of Enrollment United States | 160 participants | 78 participants | 82 participants |
| Sex: Female, Male Female | 298 Participants | 148 Participants | 150 Participants |
| Sex: Female, Male Male | 183 Participants | 93 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 240 | 0 / 241 |
| other Total, other adverse events | 84 / 240 | 37 / 241 |
| serious Total, serious adverse events | 0 / 240 | 1 / 241 |
Outcome results
Primary
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The Montgomery-Åsberg Depression Rating Scale is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.
Time frame: Day 43
Population: Combined MDD and Bipolar Depression Mixed Features Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -18.1 score on a scale | Standard Error 0.71 |
| Placebo | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -12.4 score on a scale | Standard Error 0.7 |
p-value: <0.000195% CI: [-7.6, -3.84]Mixed Effects Model for Repeated Measure
Primary
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The Montgomery-Åsberg Depression Rating Scale is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.
Time frame: Day 43
Population: Bipolar Depression Mixed Features Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -17.7 score on a scale | Standard Error 1 |
| Placebo | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -12.0 score on a scale | Standard Error 0.96 |
p-value: <0.000195% CI: [-8.29, -3.05]Mixed Effects Model for Repeated Measure
Primary
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The Montgomery-Åsberg Depression Rating Scale is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.
Time frame: Day 43
Population: MDD Mixed Features Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -18.2 score on a scale | Standard Error 0.95 |
| Placebo | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -12.2 score on a scale | Standard Error 0.96 |
p-value: <0.000195% CI: [-8.61, -3.29]Mixed Effects Model for Repeated Measure
Primary
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The Montgomery-Åsberg Depression Rating Scale is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.
Time frame: Day 43
Population: Overall Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -17.7 score on a scale | Standard Error 0.64 |
| Placebo | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -12.1 score on a scale | Standard Error 0.63 |
p-value: <0.000195% CI: [-7.25, -3.88]Mixed Effects Model for Repeated Measure
Secondary
Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S)
The Clinical Global Impression Scale-Severity is a clinician-rated scale to assess a patient's overall mental health. The scale ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Time frame: Day 43
Population: Combined MDD and Bipolar Depression Mixed Features Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42mg | Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) | -1.8 score on a scale | Standard Error 0.08 |
| Placebo | Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) | -1.2 score on a scale | Standard Error 0.08 |
p-value: <0.000195% CI: [-0.81, -0.39]Mixed Effects Model of Repeated Measure
Secondary
Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S)
The Clinical Global Impression Scale-Severity is a clinician-rated scale to assess a patient's overall mental health. The scale ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Time frame: Day 43
Population: Bipolar Depression Mixed Features Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42mg | Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) | -1.8 score on a scale | Standard Error 0.11 |
| Placebo | Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) | -1.2 score on a scale | Standard Error 0.11 |
p-value: <0.000195% CI: [-0.91, -0.31]Mixed Effects Model for Repeated Measure
Secondary
Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S)
The Clinical Global Impression Scale-Severity is a clinician-rated scale to assess a patient's overall mental health. The scale ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Time frame: Day 43
Population: MDD Mixed Features Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42mg | Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) | -1.7 score on a scale | Standard Error 0.11 |
| Placebo | Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) | -1.1 score on a scale | Standard Error 0.11 |
p-value: 0.000395% CI: [-0.89, -0.27]Mixed Effects Model for Repeated Measure
Secondary
Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S)
The Clinical Global Impression Scale-Severity is a clinician-rated scale to assess a patient's overall mental health. The scale ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Time frame: Day 43
Population: Overall Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42mg | Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) | -1.7 score on a scale | Standard Error 0.07 |
| Placebo | Clinical From Baseline in Clinical Global Impression Scale - Severity (CGI-S) | -1.1 score on a scale | Standard Error 0.07 |
p-value: <0.000195% CI: [-0.82, -0.44]Mixed Effects Model for Repeated Measure