Bipolar Depression
Conditions
Brief summary
The study will evaluate the efficacy and safety of ITI-007 adjunctive to lithium or valproate 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
DRUGPlacebo
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
* 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 * treatment with either lithium or valproate and inadequate therapeutic response of depressive symptoms
Exclusion criteria
* any subject unable to provide informed consent * any female subject who is pregnant or breastfeeding * 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-Severity (CGI-BP-S) Depression Score | Baseline to Day 43 | The Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) Depression Score is a clinician-rated scale that measures the patient's current state of depression from 1 (not ill at all) to 7 (among the most extremely ill). |
Countries
Bulgaria, Russia, Serbia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lumateperone 28 mg (ITI-007 40 mg Tosylate) Lumateperone 28 mg (ITI-007 40 mg tosylate) administered orally as capsules once daily for 6 weeks
Lumateperone 28 mg | 176 |
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) Lumateperone 42 mg (ITI-007 60 mg tosylate) administered orally as capsules once daily for 6 weeks
Lumateperone 42 mg | 177 |
| Placebo Placebo administered orally as visually-matched capsules once daily for 6 weeks
Placebo | 175 |
| Total | 528 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 15 | 5 |
| Overall Study | Lack of Efficacy | 3 | 8 | 5 |
| Overall Study | Lost to Follow-up | 3 | 5 | 2 |
| Overall Study | Other | 0 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 12 | 4 | 4 |
| Overall Study | Withdrawal by Subject | 7 | 11 | 7 |
Baseline characteristics
| Characteristic | Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Total | Placebo | Lumateperone 42 mg (ITI-007 60 mg Tosylate) |
|---|---|---|---|---|
| Age, Continuous | 44.0 years STANDARD_DEVIATION 13.56 | 44.6 years STANDARD_DEVIATION 13.02 | 45.1 years STANDARD_DEVIATION 12.93 | 44.7 years STANDARD_DEVIATION 12.6 |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 32.5 units on a scale STANDARD_DEVIATION 5.55 | 32.3 units on a scale STANDARD_DEVIATION 5.24 | 32.2 units on a scale STANDARD_DEVIATION 5.23 | 32.3 units on a scale STANDARD_DEVIATION 4.96 |
| Race/Ethnicity, Customized Asian | 0 Participants | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 22 Participants | 56 Participants | 14 Participants | 20 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 153 Participants | 466 Participants | 157 Participants | 156 Participants |
| Region of Enrollment Bulgaria | 49 participants | 142 participants | 48 participants | 45 participants |
| Region of Enrollment Russia | 31 participants | 104 participants | 36 participants | 37 participants |
| Region of Enrollment Serbia | 16 participants | 52 participants | 20 participants | 16 participants |
| Region of Enrollment Ukraine | 21 participants | 57 participants | 15 participants | 21 participants |
| Region of Enrollment United States | 59 participants | 173 participants | 56 participants | 58 participants |
| Sex: Female, Male Female | 101 Participants | 308 Participants | 98 Participants | 109 Participants |
| Sex: Female, Male Male | 75 Participants | 220 Participants | 77 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 176 | 0 / 177 | 0 / 175 |
| other Total, other adverse events | 50 / 176 | 47 / 177 | 28 / 175 |
| serious Total, serious adverse events | 0 / 176 | 1 / 177 | 0 / 175 |
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 28 mg (ITI-007 40 mg Tosylate) | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -16.2 score on a scale | Standard Error 0.79 |
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -16.9 score on a scale | Standard Error 0.81 |
| Placebo | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -14.5 score on a scale | Standard Error 0.79 |
p-value: 0.02195% CI: [-4.42, -0.37]Mixed Effects Model for Repeated Measure
p-value: 0.09995% CI: [-3.65, 0.32]Mixed Effects Model for Repeated Measure
Secondary
Change From Baseline in Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) Depression Score
The Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) Depression Score is a clinician-rated scale that measures the patient's current state of depression from 1 (not ill at all) to 7 (among the most extremely ill).
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 28 mg (ITI-007 40 mg Tosylate) | Change From Baseline in Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) Depression Score | -1.7 score on a scale | Standard Error 0.09 |
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Change From Baseline in Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) Depression Score | -1.8 score on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) Depression Score | -1.5 score on a scale | Standard Error 0.09 |
p-value: 0.00895% CI: [-0.59, -0.09]Mixed Effects Model for Repeated Measure
p-value: 0.0495% CI: [-0.5, -0.01]Mixed Effects Model for Repeated Measure