Bipolar Depression
Conditions
Brief summary
The study will evaluate the efficacy and safety of ITI-007 in a randomized, double-blind, parallel-group, placebo-controlled, multi-center study in patients diagnosed with Bipolar I or Bipolar II disorder having a major depressive episode.
Interventions
DRUGLumateperone
Lumateperone 42 mg (ITI-007 60 mg tosylate)
OTHERPlacebo
Placebo
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, with a clinical diagnosis of Bipolar I or Bipolar II disorder * experiencing a current major depressive episode * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | Baseline to Day 43 | The Montgomery-Åsberg Depression Rating Scale (MADRS) 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 |
|---|---|---|
| Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score | Baseline to Day 43 | The Clinical Global Impression Scale, Bipolar version (CGI-BP-S) total score is a clinician-rated scale that measures the patient's current illness state on a 3 to 21 point scale where a higher score is associated with greater illness severity.. Each domain (depression, mania, and overall illness) is rated from 1 (not ill at all) to 7 (among the most extremely ill) and the 3 scores are added to obtain the total score. |
| Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score | Baseline to Day 43 | The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 14 item patient self-reported questionnaire that assesses how satisfied a patient is, using a 5-point scale from 1-very poor to 5-very good. |
Countries
Bulgaria, Colombia, Russia, Serbia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lumateperone Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks
Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate) | 188 |
| Placebo Placebo administered once daily every evening for 6 weeks
Placebo: Placebo | 189 |
| Total | 377 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 5 |
| Overall Study | Lack of Efficacy | 2 | 4 |
| Overall Study | LTFU | 2 | 1 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 9 |
Baseline characteristics
| Characteristic | Lumateperone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.7 years STANDARD_DEVIATION 14.09 | 44.1 years STANDARD_DEVIATION 12.87 | 44.9 years STANDARD_DEVIATION 13.5 |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 30.8 units on a scale STANDARD_DEVIATION 4.92 | 30.2 units on a scale STANDARD_DEVIATION 4.65 | 30.5 units on a scale STANDARD_DEVIATION 4.79 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 14 Participants | 15 Participants | 29 Participants |
| Race/Ethnicity, Customized Caucasian/White | 173 Participants | 171 Participants | 344 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 3 Participants | 3 Participants |
| Region of Enrollment Bulgaria | 49 participants | 43 participants | 92 participants |
| Region of Enrollment Colombia | 1 participants | 2 participants | 3 participants |
| Region of Enrollment Russia | 32 participants | 34 participants | 66 participants |
| Region of Enrollment Serbia | 6 participants | 13 participants | 19 participants |
| Region of Enrollment Ukraine | 49 participants | 38 participants | 87 participants |
| Region of Enrollment United States | 51 participants | 59 participants | 110 participants |
| Sex: Female, Male Female | 99 Participants | 120 Participants | 219 Participants |
| Sex: Female, Male Male | 89 Participants | 69 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 188 | 0 / 189 |
| other Total, other adverse events | 58 / 188 | 31 / 189 |
| serious Total, serious adverse events | 1 / 188 | 0 / 189 |
Outcome results
Primary
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The Montgomery-Åsberg Depression Rating Scale (MADRS) 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: Baseline to Day 43
Population: Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -16.70 score on a scale | Standard Error 0.693 |
| Placebo | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -12.12 score on a scale | Standard Error 0.677 |
p-value: <0.000195% CI: [-6.34, -2.83]Mixed Effects Model for Repeated Measure
Secondary
Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score
The Clinical Global Impression Scale, Bipolar version (CGI-BP-S) total score is a clinician-rated scale that measures the patient's current illness state on a 3 to 21 point scale where a higher score is associated with greater illness severity.. Each domain (depression, mania, and overall illness) is rated from 1 (not ill at all) to 7 (among the most extremely ill) and the 3 scores are added to obtain the total score.
Time frame: Baseline to Day 43
Population: Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone | Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score | -3.48 score on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score | -2.54 score on a scale | Standard Error 0.167 |
p-value: <0.000195% CI: [-1.37, -0.51]Mixed Effects Model for Repeated Measure
Secondary
Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score
The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 14 item patient self-reported questionnaire that assesses how satisfied a patient is, using a 5-point scale from 1-very poor to 5-very good.
Time frame: Baseline to Day 43
Population: Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone | Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score | 19.4 Percent Score | Standard Error 1.49 |
| Placebo | Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score | 14.9 Percent Score | Standard Error 1.45 |
p-value: 0.00595% CI: [1.42, 7.69]ANCOVA