Major Depressive Disorder
Conditions
Keywords
MDD
Brief summary
The objective of this study is to evaluate the efficacy, safety and tolerability of cariprazine as an adjunctive treatment to antidepressant therapy (ADT) in patients with MDD who have had an inadequate response to antidepressants alone.
Interventions
DRUGCariprazine
Cariprazine supplied in capsules
DRUGPlacebo
Placebo supplied in capsules
Sponsors
AbbVie
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
* Written informed consent has been obtained. * Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health and Research Study Information \[US sites\] and written Data Protection consent \[EU sites\]). * Patient must be an outpatient at the time of Visit 1 (Screening). * Patient meets the DSM-5 criteria for MDD based on SCID-5, with a current major depressive episode of at least 8 weeks and not exceeding 24 months in duration at Visit 1/Screening. A diagnosis of MDD with psychotic features will be acceptable. * Diagnosis of MDD confirmed through a formal adjudication process. * Patient demonstrates ability to follow study instructions and likely to complete all required visits. * Patient must have an inadequate response, as measured by the modified ATRQ, to 1 to 3 antidepressants administered during the current episode at an adequate dose (as per package insert) and for at least 6 weeks duration, with at least one dose escalation during the current depressive episode. * Only one antidepressant (of sufficient dose per package insert and taken for at least 6 weeks) will be allowed at randomization and patients must agree to continue taking the same ADT dosing regimen through completion of Visit 6/ET. Patients who are taking more than one antidepressant at Screening, regardless of the indication, will need to discontinue all other antidepressants prior to Visit 2 (Baseline). * Male and female patients must agree to use a medically acceptable and highly effective method of birth control during the course of the entire study. * Women of childbearing potential (only) must have a negative serum β-human chorionic gonadotropin pregnancy test prior to Visit 2.
Exclusion criteria
* Diagnosis of any current psychiatric diagnosis other than MDD (including those with current intellectual development disability) with the exception of specific phobias. * Patient has a history of intolerance or hypersensitivity to cariprazine or other drugs of the same class or to rescue medications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Score Change From Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale) | Baseline and Week 6 | The MADRS is a 10-item, clinician-rated scale that evaluates the patient's depressive symptomatology during the past week. Patients 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. mITT Population included all randomized participants who had ≥1 postbaseline assessment of the MADRS total score. Number of subjects analyzed are the number of participants with data available for analyses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in the Clinical Global Impressions-Severity (CGI-S) Score | Baseline and Week 6 | The CGI-S is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with MDD population. The participant was rated on a scale from 1 to 7, where 1=normal, not at all ill and 7=among the most extremely ill participants. Higher scores indicate worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analyses. mITT Population included all randomized participants who had ≥1 postbaseline assessment of the MADRS total score. Number of subjects analyzed are the number of participants with data available for analyses. |
Countries
Bulgaria, Estonia, Germany, Hungary, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 759 participants were randomized to double-blind treatment, 757 participants received at least 1 dose of double-blind investigational product (safety population), and 751 treated participants had at least 1 postbaseline assessment of MADRS total score (modified intent-to-treat \[mITT\] population ). At the end of treatment in the Double-blind Period, participants continued on their background antidepressant therapy (ADT) and entered the Safety Follow-up Period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + ADT During the double blind treatment period (6 weeks), participants will take 1 capsule of placebo, orally, per day in addition to their ongoing ADT (Same antidepressant and dose of ADT they were on at the Visit 2 baseline).
Placebo: Placebo supplied in capsules | 253 |
| Cariprazine 1.5 mg/Day + ADT During the double blind treatment period (6 weeks), participants will take 1 capsule of cariprazine 1.5mg, orally, per day in addition to their ongoing ADT (Same antidepressant and dose of ADT they were on at the Visit 2 baseline).
Cariprazine: Cariprazine supplied in capsules | 252 |
| Cariprazine 3 mg/Day + ADT During the double blind treatment period (6 weeks), participants will take 1 capsule of cariprazine 1.5mg, orally, per day for two weeks in addition to their ongoing ADT (Same antidepressant and dose of ADT they were on at the Visit 2 baseline). They will then titrate to Cariprazine 3 mg, orally per day, in addition to their ADT starting at Visit 4 (Week 2).
Cariprazine: Cariprazine supplied in capsules | 252 |
| Total | 757 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Treatment Period (6 Weeks) | Adverse Event | 6 | 3 | 18 |
| Double-blind Treatment Period (6 Weeks) | Lack of Efficacy | 2 | 2 | 0 |
| Double-blind Treatment Period (6 Weeks) | Lost to Follow-up | 3 | 3 | 5 |
| Double-blind Treatment Period (6 Weeks) | Non-Compliance with Study Drug | 0 | 1 | 1 |
| Double-blind Treatment Period (6 Weeks) | Protocol Violation | 0 | 1 | 0 |
| Double-blind Treatment Period (6 Weeks) | Withdrawal by Subject | 13 | 11 | 9 |
| Safety Follow Up Period (4 Weeks) | Adverse Event | 0 | 0 | 1 |
| Safety Follow Up Period (4 Weeks) | Lost to Follow-up | 2 | 2 | 4 |
| Safety Follow Up Period (4 Weeks) | Reason Not Specified | 0 | 2 | 0 |
| Safety Follow Up Period (4 Weeks) | Withdrawal by Subject | 1 | 1 | 3 |
Baseline characteristics
| Characteristic | Cariprazine 3 mg/Day + ADT | Cariprazine 1.5 mg/Day + ADT | Placebo + ADT | Total |
|---|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 13.33 | 43.3 years STANDARD_DEVIATION 13.59 | 46.4 years STANDARD_DEVIATION 11.89 | 44.8 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 24 Participants | 25 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 233 Participants | 228 Participants | 228 Participants | 689 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 4 Participants | 5 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 37 Participants | 43 Participants | 110 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 215 Participants | 205 Participants | 203 Participants | 623 Participants |
| Region of Enrollment Bulgaria | 34 participants | 34 participants | 35 participants | 103 participants |
| Region of Enrollment Estonia | 9 participants | 10 participants | 10 participants | 29 participants |
| Region of Enrollment Germany | 12 participants | 12 participants | 13 participants | 37 participants |
| Region of Enrollment Hungary | 7 participants | 7 participants | 7 participants | 21 participants |
| Region of Enrollment Ukraine | 34 participants | 33 participants | 33 participants | 100 participants |
| Region of Enrollment United Kingdom | 3 participants | 3 participants | 3 participants | 9 participants |
| Region of Enrollment United States | 153 participants | 153 participants | 152 participants | 458 participants |
| Sex: Female, Male Female | 180 Participants | 191 Participants | 184 Participants | 555 Participants |
| Sex: Female, Male Male | 72 Participants | 61 Participants | 69 Participants | 202 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 253 | 0 / 252 | 0 / 252 |
| other Total, other adverse events | 39 / 253 | 68 / 252 | 62 / 252 |
| serious Total, serious adverse events | 2 / 253 | 3 / 252 | 3 / 252 |
Outcome results
Primary
Total Score Change From Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale)
The MADRS is a 10-item, clinician-rated scale that evaluates the patient's depressive symptomatology during the past week. Patients 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. mITT Population included all randomized participants who had ≥1 postbaseline assessment of the MADRS total score. Number of subjects analyzed are the number of participants with data available for analyses.
Time frame: Baseline and Week 6
Population: mITT population includes all randomized participants who had ≥ 1 postbaseline assessment of the MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + ADT | Total Score Change From Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale) | -11.5 score on a scale | Standard Error 0.7 |
| Cariprazine 1.5 mg/Day + ADT | Total Score Change From Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale) | -14.1 score on a scale | Standard Error 0.7 |
| Cariprazine 3 mg/Day + ADT | Total Score Change From Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale) | -13.1 score on a scale | Standard Error 0.7 |
p-value: 0.00595% CI: [-4.17, -0.89]MMRM
p-value: 0.072795% CI: [-3.16, 0.12]MMRM
Secondary
Change From Baseline to Week 6 in the Clinical Global Impressions-Severity (CGI-S) Score
The CGI-S is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with MDD population. The participant was rated on a scale from 1 to 7, where 1=normal, not at all ill and 7=among the most extremely ill participants. Higher scores indicate worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analyses. mITT Population included all randomized participants who had ≥1 postbaseline assessment of the MADRS total score. Number of subjects analyzed are the number of participants with data available for analyses.
Time frame: Baseline and Week 6
Population: mITT population includes all randomized participants who had ≥ 1 postbaseline assessment of the MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + ADT | Change From Baseline to Week 6 in the Clinical Global Impressions-Severity (CGI-S) Score | -1.1 score on a scale | Standard Error 0.09 |
| Cariprazine 1.5 mg/Day + ADT | Change From Baseline to Week 6 in the Clinical Global Impressions-Severity (CGI-S) Score | -1.4 score on a scale | Standard Error 0.09 |
| Cariprazine 3 mg/Day + ADT | Change From Baseline to Week 6 in the Clinical Global Impressions-Severity (CGI-S) Score | -1.3 score on a scale | Standard Error 0.09 |
p-value: 0.072795% CI: [-0.49, -0.07]MMRM
p-value: 0.094495% CI: [-0.39, 0.03]MMRM