Bipolar Depression
Conditions
Brief summary
The study will evaluate the efficacy and safety of ITI-007 (Lumateperone) in patients diagnosed with Bipolar I or Bipolar II disorder having a major depressive episode. The study will be conducted in two parts, Part A and Part B. Part A is a randomized, double-blind, placebo-controlled study. In Part B, patients who safely complete participation in part A may be enrolled in an open-label extension.
Interventions
DRUGITI-007 (Lumateperone)
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
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 Major
Exclusion criteria
* any subject unable to provide informed consent * 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 to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | 6 weeks | 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 |
|---|---|
| Time to First Sustained Response in Reduction of MADRS Total Score | 6 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 175 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | Day 175 | The MADRS total score from baseline to Day 175 for patients that rolled over into the extension portion of the study (Part B) |
| Adverse Events | Day 175 | Incidence of Treatment-Emergent Adverse Events from baseline to Day 175 for patients that rolled over into the extension portion of the study (Part B) |
Countries
United States
Participant flow
Pre-assignment details
Part A includes all patients who signed the informed consent and were randomized in to the 6 week double-blind treatment period. 554 patients were randomized; 549 patients received study drug and are included in the safety population. Part B includes all patients who signed the informed consent and received open-label study drug for up to 6 months.
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
ITI-007 (Lumateperone) | 180 |
| 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 (ITI-007) | 184 |
| Placebo Placebo administered orally as visually-matched capsules once daily for 6 weeks
Placebo | 185 |
| Total | 549 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A (6 Week Double-Blind Treatment) | Adverse Event | 13 | 15 | 4 |
| Part A (6 Week Double-Blind Treatment) | Lack of Efficacy | 2 | 4 | 2 |
| Part A (6 Week Double-Blind Treatment) | Lost to Follow-up | 12 | 28 | 10 |
| Part A (6 Week Double-Blind Treatment) | non-compliant with site request | 0 | 1 | 0 |
| Part A (6 Week Double-Blind Treatment) | Physician Decision | 2 | 3 | 4 |
| Part A (6 Week Double-Blind Treatment) | Protocol Violation | 13 | 10 | 14 |
| Part A (6 Week Double-Blind Treatment) | Withdrawal by Subject | 15 | 11 | 14 |
| Part B (6 Month Open-Label Treatment) | Adverse Event | 0 | 12 | 0 |
| Part B (6 Month Open-Label Treatment) | Lack of Efficacy | 0 | 4 | 0 |
| Part B (6 Month Open-Label Treatment) | Lost to Follow-up | 0 | 11 | 0 |
| Part B (6 Month Open-Label Treatment) | Physician Decision | 0 | 1 | 0 |
| Part B (6 Month Open-Label Treatment) | Protocol Violation | 0 | 8 | 0 |
| Part B (6 Month Open-Label Treatment) | Withdrawal by Subject | 0 | 17 | 0 |
Baseline characteristics
| Characteristic | Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 40.5 years STANDARD_DEVIATION 12.12 | 42.7 years STANDARD_DEVIATION 11.85 | 42.3 years STANDARD_DEVIATION 13.13 | 41.9 years STANDARD_DEVIATION 12.4 |
| Montgomery Asberg Depression Rating Scale (MADRS) | 35.8 units on a scale STANDARD_DEVIATION 6.08 | 35.9 units on a scale STANDARD_DEVIATION 5.79 | 34.7 units on a scale STANDARD_DEVIATION 5.84 | 35.4 units on a scale STANDARD_DEVIATION 5.92 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 3 participants | 6 participants |
| Race/Ethnicity, Customized Black or African American | 75 participants | 72 participants | 80 participants | 227 participants |
| Race/Ethnicity, Customized Multiple | 4 participants | 1 participants | 1 participants | 6 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Not Reported | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 100 participants | 106 participants | 98 participants | 304 participants |
| Sex: Female, Male Female | 109 Participants | 111 Participants | 114 Participants | 334 Participants |
| Sex: Female, Male Male | 71 Participants | 73 Participants | 71 Participants | 215 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 180 | 0 / 184 | 1 / 185 | 0 / 127 |
| other Total, other adverse events | 72 / 180 | 67 / 184 | 31 / 185 | 55 / 127 |
| serious Total, serious adverse events | 5 / 180 | 0 / 184 | 1 / 185 | 4 / 127 |
Outcome results
Primary
Change From Baseline to Day 43 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: 6 weeks
Population: Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and who 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 to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -18.9 score on a scale | Standard Error 1.11 |
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Change From Baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -20.7 score on a scale | Standard Error 1.16 |
| Placebo | Change From Baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -19.7 score on a scale | Standard Error 1.11 |
p-value: 0.51495% CI: [-1.83, 3.53]Mixed Effects Model for Repeated Measure
p-value: 0.89595% CI: [-3.73, 1.79]Mixed Effects Model for Repeated Measure
Secondary
Time to First Sustained Response in Reduction of MADRS Total Score
Time frame: 6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Time to First Sustained Response in Reduction of MADRS Total Score | 43 days |
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Time to First Sustained Response in Reduction of MADRS Total Score | 38 days |
| Placebo | Time to First Sustained Response in Reduction of MADRS Total Score | 37 days |
p-value: 0.99395% CI: [0.712, 1.4]Regression, Cox
p-value: 0.66595% CI: [0.657, 1.307]Regression, Cox
Other Pre-specified
Adverse Events
Incidence of Treatment-Emergent Adverse Events from baseline to Day 175 for patients that rolled over into the extension portion of the study (Part B)
Time frame: Day 175
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Adverse Events | Headache | 26 Participants |
| Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Adverse Events | Dry Mouth | 15 Participants |
| Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Adverse Events | Dizziness | 13 Participants |
| Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Adverse Events | Nausea | 13 Participants |
| Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Adverse Events | Somnolence | 11 Participants |
| Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Adverse Events | Anxiety | 10 Participants |
| Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Adverse Events | Irritability | 8 Participants |
Other Pre-specified
Change From Baseline to Day 175 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The MADRS total score from baseline to Day 175 for patients that rolled over into the extension portion of the study (Part B)
Time frame: Day 175
Population: Safety Analysis Set - all patients who received at least 1 dose of study medication in Part B
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 28 mg (ITI-007 40 mg Tosylate) | Change From Baseline to Day 175 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -8.9 units on a scale | Standard Deviation 10.76 |