Depression, Bipolar
Conditions
Keywords
Bipolar I disorder, Bipolar depression, Depression, Bipolar disorder
Brief summary
The objective of this study was to evaluate the efficacy, safety, and tolerability of cariprazine relative to placebo for the treatment of participants with bipolar depression.
Interventions
DRUGPlacebo
Placebo was supplied in capsules.
DRUGCariprazine
Cariprazine was supplied in capsules.
Sponsors
Gedeon Richter Ltd.
Forest Laboratories
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Participants who have provided informed consent prior to any study specific procedures. * Participants currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder as confirmed by the Structured Clinical Interview (SCID) with a current with a current major depressive episode of at least 4 weeks and not exceeding 12 months in duration. * Participants with normal physical examination, laboratory, vital signs, and/or echocardiogram (ECG). * Verified previous manic or mixed episode. * Participants with a total Hamilton Rating Scale for Depression (HAMD)-17 score ≥ 20. * Participants with a HAMD-17 item 1 score ≥ 2. * Participants with a Clinical Global Impression of Severity (CGI-S) score ≥ 4.
Exclusion criteria
* Participants with a DSM-IV-TR diagnosis of an axis I disorder other than bipolar I disorder that was the primary focus of treatment within the previous 6 months. * Women who are pregnant or breast feeding * Participants with Young Mania Rating Scale (YMRS) total score \> 10 * Participants who have dementia, mental retardation, schizophrenia/schizoaffective disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Montgomery-Åsberg Depression Rating Scale Total Score at Week 6 | Baseline to Week 6 | The Montgomery-Åsberg Depression Rating Scale is a 10-item, clinician-rated scale that evaluates the participant's depressive symptomatology during the past week. Participants are rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item is scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity. The scores on the 10 items are summed for a total score that can range from 0 to 60. A higher score indicates greater depression. A negative change score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Clinical Global Impressions-Severity Total Score at Week 6 | Baseline to Week 6 | The Clinical Global Impressions-Severity scale is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of illness in other participants the physician has observed. The participant is rated on a scale from 1 to 7 with 1 indicating a normal state and 7 indicating among the most extremely ill participants. A higher score indicates greater illness. A negative change score indicates improvement. |
Countries
Bulgaria, Canada, Colombia, Russia, Ukraine, United States
Participant flow
Recruitment details
Adult participants with a diagnosis of bipolar I disorder with a current major depressive episode were considered for participation in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo orally once a day for 8 weeks. | 145 |
| Cariprazine 0.75 mg Participants received cariprazine 0.5 mg orally once on Days 1-2 and cariprazine 0.75 mg orally once a day starting on Day 3 for the remainder of the 8 week treatment period. | 141 |
| Cariprazine 1.5 mg Participants received cariprazine 0.5 mg orally once on Days 1-2, cariprazine 0.75 mg orally once on Days 3-4, cariprazine 1.0 mg orally once on Days 5-7, and cariprazine 1.5 mg orally once a day starting on Day 8 for the remainder of the 8 week treatment period. | 146 |
| Cariprazine 3.0 mg Participants received cariprazine 0.5 mg orally once on Days 1-2, cariprazine 0.75 mg orally once on Days 3-4, cariprazine 1.0 mg orally once on Days 5-7, cariprazine 1.5 mg orally on Days 8-14, and cariprazine 3.0 mg orally once a day starting on Day 15 for the remainder of the 8 week treatment period. | 146 |
| Total | 578 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 15 | 12 | 12 | 17 |
| Overall Study | Did Not Receive Treatment | 3 | 2 | 1 | 0 |
| Overall Study | Insufficient Therapeutic Response | 5 | 5 | 2 | 4 |
| Overall Study | Lost to Follow-up | 4 | 8 | 7 | 9 |
| Overall Study | Other Miscellaneous Reasons | 0 | 2 | 1 | 0 |
| Overall Study | Protocol Violation | 5 | 2 | 3 | 7 |
| Overall Study | Withdrawal of Consent | 11 | 9 | 4 | 15 |
Baseline characteristics
| Characteristic | Placebo | Cariprazine 0.75 mg | Cariprazine 1.5 mg | Cariprazine 3.0 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 43.6 years STANDARD_DEVIATION 12 | 40.1 years STANDARD_DEVIATION 11.2 | 40.9 years STANDARD_DEVIATION 11.4 | 42.8 years STANDARD_DEVIATION 10.8 | 41.9 years STANDARD_DEVIATION 11.4 |
| Body Mass Index (BMI) | 27.81 kg/m^2 STANDARD_DEVIATION 5.27 | 28.42 kg/m^2 STANDARD_DEVIATION 5.71 | 28.44 kg/m^2 STANDARD_DEVIATION 5.39 | 28.28 kg/m^2 STANDARD_DEVIATION 5.64 | 28.24 kg/m^2 STANDARD_DEVIATION 5.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 13 Participants | 11 Participants | 12 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 133 Participants | 128 Participants | 135 Participants | 134 Participants | 530 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African-American | 30 Participants | 26 Participants | 30 Participants | 26 Participants | 112 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 110 Participants | 111 Participants | 109 Participants | 113 Participants | 443 Participants |
| Sex: Female, Male Female | 89 Participants | 91 Participants | 92 Participants | 88 Participants | 360 Participants |
| Sex: Female, Male Male | 56 Participants | 50 Participants | 54 Participants | 58 Participants | 218 Participants |
| Waist circumference | 91.40 cm STANDARD_DEVIATION 14.24 | 93.32 cm STANDARD_DEVIATION 15.45 | 93.38 cm STANDARD_DEVIATION 14.55 | 93.24 cm STANDARD_DEVIATION 15.4 | 92.83 cm STANDARD_DEVIATION 14.9 |
| Weight | 79.98 kg STANDARD_DEVIATION 17.08 | 80.81 kg STANDARD_DEVIATION 18.36 | 81.43 kg STANDARD_DEVIATION 16.79 | 81.45 kg STANDARD_DEVIATION 17.86 | 80.92 kg STANDARD_DEVIATION 17.49 |
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 / 145 | 0 / 141 | 0 / 146 | 0 / 146 |
| other Total, other adverse events | 42 / 145 | 43 / 141 | 51 / 146 | 56 / 146 |
| serious Total, serious adverse events | 5 / 145 | 1 / 141 | 2 / 146 | 2 / 146 |
Outcome results
Primary
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale Total Score at Week 6
The Montgomery-Åsberg Depression Rating Scale is a 10-item, clinician-rated scale that evaluates the participant's depressive symptomatology during the past week. Participants are rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item is scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity. The scores on the 10 items are summed for a total score that can range from 0 to 60. A higher score indicates greater depression. A negative change score indicates improvement.
Time frame: Baseline to Week 6
Population: Intent-to-treat population: All randomized participants who took at least 1 dose of investigational product and had at least 1 post-Baseline assessment of the Montgomery-Åsberg Depression Rating Scale.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Montgomery-Åsberg Depression Rating Scale Total Score at Week 6 | -11.1 units on a scale | Standard Error 0.9 |
| Cariprazine 0.75 mg | Change From Baseline in the Montgomery-Åsberg Depression Rating Scale Total Score at Week 6 | -13.0 units on a scale | Standard Error 0.9 |
| Cariprazine 1.5 mg | Change From Baseline in the Montgomery-Åsberg Depression Rating Scale Total Score at Week 6 | -15.1 units on a scale | Standard Error 0.8 |
| Cariprazine 3.0 mg | Change From Baseline in the Montgomery-Åsberg Depression Rating Scale Total Score at Week 6 | -13.7 units on a scale | Standard Error 0.9 |
p-value: 0.129295% CI: [-4.3, 0.5]Repeated measures mixed-effects model
p-value: 0.00195% CI: [-6.3, -1.6]Repeated measures mixed-effects model
p-value: 0.037495% CI: [-4.9, -0.1]Repeated measures mixed-effects model
Secondary
Change From Baseline in the Clinical Global Impressions-Severity Total Score at Week 6
The Clinical Global Impressions-Severity scale is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of illness in other participants the physician has observed. The participant is rated on a scale from 1 to 7 with 1 indicating a normal state and 7 indicating among the most extremely ill participants. A higher score indicates greater illness. A negative change score indicates improvement.
Time frame: Baseline to Week 6
Population: Intent-to-treat population: All randomized participants who took at least 1 dose of investigational product and had at least 1 post-Baseline assessment of the Montgomery-Åsberg Depression Rating Scale.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Clinical Global Impressions-Severity Total Score at Week 6 | -1.0 units on a scale | Standard Error 0.1 |
| Cariprazine 0.75 mg | Change From Baseline in the Clinical Global Impressions-Severity Total Score at Week 6 | -1.1 units on a scale | Standard Error 0.1 |
| Cariprazine 1.5 mg | Change From Baseline in the Clinical Global Impressions-Severity Total Score at Week 6 | -1.4 units on a scale | Standard Error 0.1 |
| Cariprazine 3.0 mg | Change From Baseline in the Clinical Global Impressions-Severity Total Score at Week 6 | -1.3 units on a scale | Standard Error 0.1 |
Comparison: The analysis included treatment group, pooled study center, visit, and treatment-group-by-visit interaction as fixed effects and the baseline value and baseline value-by-visit interaction as covariates.p-value: 0.302595% CI: [-0.4, 0.1]Repeated measures mixed-effects model
Comparison: The analysis included treatment group, pooled study center, visit, and treatment-group-by-visit interaction as fixed effects and the baseline value and baseline value-by-visit interaction as covariates.p-value: 0.004495% CI: [-0.6, -0.2]Repeated measures mixed-effects model
Comparison: The analysis included treatment group, pooled study center, visit, and treatment-group-by-visit interaction as fixed effects and the baseline value and baseline value-by-visit interaction as covariates.p-value: 0.048995% CI: [-0.5, 0]Repeated measures mixed-effects model