Bipolar Depression
Conditions
Keywords
bipolar, depression
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of cariprazine in the treatment of outpatients with bipolar depression.
Interventions
DRUGcariprazine
Drug: cariprazine (0.25 - 0.75 mg/day)
DRUGplacebo
placebo capsules, oral administration, once daily dosing
Sponsors
Gedeon Richter Ltd.
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Men and women, 18-65 years old * Currently meet the DSM-IV-TR criteria for Bipolar I or II Disorder without psychotic features, with a current depressive episode * A verified previous manic, hypomanic, or mixed episode * Score of 20 or higher on the HAMD-17 * Score of 2 or higher on Item 1 of the HAMD
Exclusion criteria
* Score greater than 12 on the Young Mania Rating Scale * Eight or more episodes of a mood disturbance (depression, mania, hypomania, or mixed state) within the 12 months prior to Visit 1 * Principal DSM-IV-TR-based diagnosis of an axis I disorder other than bipolar disorder (a secondary diagnosis of comorbid Generalized Anxiety Disorder, Social Anxiety Disorder, or specific phobias is acceptable)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) | Baseline to Week 8 | The patient is rated on a scale from 0-6 on 10 items. Apparent sadness, reported sadness, lassitude, pessimistic thoughts, inner tension, suicidal thoughts, reduced sleep and appetite, concentration difficulties, inability to feel. The overall MADRS score ranges from 0-60, with 0 meaning no symptoms and score of 60 meaning maximum severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Baseline in Clinical Global Impressions-Improvement ( CGI-I ) | Baseline to Week 8 | The patient was rated on a scale from 1 to 7, with 1 indicating the patient was very much improved and 7 indicating that the patient was very much worse. |
Countries
United States
Participant flow
Pre-assignment details
233 patients were randomized to receive double-blind treatment, 227 patients received at least 1 dose of double-blind treatment and were included in safety Population
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo capsules, orally administered for 8 weeks | 77 |
| 0.25 to 0.75 mg Cariprazine Cariprazine capsules 0.25 to 0.75 mg was orally administrated once daily for 8 weeks | 75 |
| 1.5 to 3.0 mg Cariprazine Cariprazine capsules 1.5 to 3.0 mg was orally administrated once daily for 8 weeks | 75 |
| Total | 227 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 7 |
| Overall Study | Lack of Efficacy | 4 | 1 | 2 |
| Overall Study | Lost to Follow-up | 5 | 5 | 6 |
| Overall Study | pregnancy,moving away and surgery | 1 | 0 | 2 |
| Overall Study | Protocol Violation | 2 | 2 | 7 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo | 0.25 to 0.75 mg Cariprazine | 1.5 to 3.0 mg Cariprazine |
|---|---|---|---|---|
| Age, Continuous | 38.9 Years STANDARD_DEVIATION 11.2 | 40.6 Years STANDARD_DEVIATION 10.7 | 37.4 Years STANDARD_DEVIATION 10.7 | 38.8 Years STANDARD_DEVIATION 12.1 |
| Age, Customized < 20 | 4 Participants | 1 Participants | 1 Participants | 2 Participants |
| Age, Customized 20, 30 | 50 Participants | 11 Participants | 21 Participants | 18 Participants |
| Age, Customized 30, 40 | 64 Participants | 24 Participants | 20 Participants | 20 Participants |
| Age, Customized 40, 50 | 66 Participants | 23 Participants | 23 Participants | 20 Participants |
| Age, Customized 50, 60 | 40 Participants | 17 Participants | 10 Participants | 13 Participants |
| Age, Customized ≥ 60 | 3 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 3 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 214 Participants | 74 Participants | 71 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 2 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 46 Participants | 19 Participants | 16 Participants | 11 Participants |
| Race/Ethnicity, Customized Caucasian | 172 Participants | 54 Participants | 56 Participants | 62 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Non-Caucasian | 55 Participants | 23 Participants | 19 Participants | 13 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Sex/Gender, Customized Female | 145 participant | 46 participant | 48 participant | 51 participant |
| Sex/Gender, Customized Male | 82 participant | 31 participant | 27 participant | 24 participant |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 51 / 77 | 48 / 75 | 52 / 75 |
| serious Total, serious adverse events | 2 / 77 | 2 / 75 | 2 / 75 |
Outcome results
Primary
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS)
The patient is rated on a scale from 0-6 on 10 items. Apparent sadness, reported sadness, lassitude, pessimistic thoughts, inner tension, suicidal thoughts, reduced sleep and appetite, concentration difficulties, inability to feel. The overall MADRS score ranges from 0-60, with 0 meaning no symptoms and score of 60 meaning maximum severity.
Time frame: Baseline to Week 8
Population: of the 227 included to the safety population, the mixed-effects model for repeated measures (MMRM) of the Intent to Treat study population was 60 for placebo, 64 for 0.25-0.75 mg Cariprazine and 54 for 1.5 to 3.0 mg Cariprazine
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) | 29.9 Score on scale | Standard Error 0.6 |
| 0.25 to 0.75 mg Cariprazine | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) | 30.2 Score on scale | Standard Error 0.6 |
| 1.5 to 3.0 mg Cariprazine | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) | 30.9 Score on scale | Standard Error 0.6 |
p-value: 0.7408ANCOVA
p-value: 0.9961ANCOVA
Secondary
Change in Baseline in Clinical Global Impressions-Improvement ( CGI-I )
The patient was rated on a scale from 1 to 7, with 1 indicating the patient was very much improved and 7 indicating that the patient was very much worse.
Time frame: Baseline to Week 8
Population: of the 227 included to the safety population, the mixed-effects model for repeated measures (MMRM) of the Intent to Treat study population was 60 for placebo, 64 for 0.25-0.75 mg Cariprazine and 53 for 1.5 to 3.0 mg Cariprazine
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Baseline in Clinical Global Impressions-Improvement ( CGI-I ) | 2.1 Score on Scale | Standard Error 0.1 |
| 0.25 to 0.75 mg Cariprazine | Change in Baseline in Clinical Global Impressions-Improvement ( CGI-I ) | 2.1 Score on Scale | Standard Error 0.1 |
| 1.5 to 3.0 mg Cariprazine | Change in Baseline in Clinical Global Impressions-Improvement ( CGI-I ) | 2.1 Score on Scale | Standard Error 0.2 |
p-value: 0.3441ANCOVA
p-value: 0.2683ANCOVA