Major Depressive Disorder
Conditions
Keywords
MDD, Major Depressive Disorder
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
Interventions
ADT such as bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, paroxetine or vilazodone as prescribed by the physician.
DRUGCariprazine
Cariprazine capsules 1.5 to 4.5 mg/day
DRUGPlacebo
Dose-matched placebo capsule once per day
Sponsors
Gedeon Richter Ltd.
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients who have provided consent prior to any specific procedure * Meet the The Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria for Major Depressive Disorder (MDD) * Have a minimum score of 20 on 17-Item Hamilton Depression (HAMD-17) rating scale at Visits 1 and 2
Exclusion criteria
* Patients who do not meet DSM-IV-TR criteria for MDD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline in the Double-Blind Period | Baseline (Week 8) | The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Patients are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60. |
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in the Double-Blind Period | Baseline (Week 8) to Week 16 | The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Participants are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60. A negative change from Baseline indicates improvement. Mixed-effects model for repeated measures (MMRM) with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Sheehan Disability Scale (SDS) Score in the Double-Blind Period | Baseline (Week 8) to Week 16 | The Sheehan Disability Scale (SDS) is a 3-item patient-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum from 0 (no impairment) to 10 (most severe). The 3 individual scores are summed for a total possible score of 0 (unimpaired) to 30 (highly impaired). A negative change from Baseline indicates improvement. MMRM with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses. |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
1022 patients participated in an 8 week open label antidepression therapy (ADT) + single blind placebo lead-in period. 530 patients who did not respond were randomized to receive ADT or cariprazine + ADT in the double-blind period and non-responders continued ADT + Placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + ADT Lead-in Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks. | 1,022 |
| Total | 1,022 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind or Continued Treatment | Adverse Event | 0 | 3 | 23 | 2 |
| Double-Blind or Continued Treatment | Did not ingest Double-Blind Treatment | 0 | 3 | 0 | 0 |
| Double-Blind or Continued Treatment | Lost to Follow-up | 0 | 7 | 10 | 10 |
| Double-Blind or Continued Treatment | Other Reason Not Specified | 0 | 1 | 0 | 3 |
| Double-Blind or Continued Treatment | Protocol Violation | 0 | 14 | 12 | 19 |
| Double-Blind or Continued Treatment | Study or Site Terminated by Sponsor | 0 | 0 | 0 | 1 |
| Double-Blind or Continued Treatment | Withdrawal of consent | 0 | 11 | 11 | 13 |
| Placebo + ADT Lead-in Period | Adverse Event | 41 | 0 | 0 | 0 |
| Placebo + ADT Lead-in Period | Insufficient therapeutic response | 6 | 0 | 0 | 0 |
| Placebo + ADT Lead-in Period | Lost to Follow-up | 34 | 0 | 0 | 0 |
| Placebo + ADT Lead-in Period | Other Reason Not Specified | 10 | 0 | 0 | 0 |
| Placebo + ADT Lead-in Period | Protocol Violation | 74 | 0 | 0 | 0 |
| Placebo + ADT Lead-in Period | Site Terminated by Sponsor | 1 | 0 | 0 | 0 |
| Placebo + ADT Lead-in Period | Withdrawal of Consent | 49 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo + ADT Lead-in |
|---|---|
| Age, Continuous | 44.1 years STANDARD_DEVIATION 12 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 234 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 788 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 8 Participants |
| Race/Ethnicity, Customized Race Asian | 18 Participants |
| Race/Ethnicity, Customized Race Black or African American | 250 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants |
| Race/Ethnicity, Customized Race White | 741 Participants |
| Sex: Female, Male Female | 673 Participants |
| Sex: Female, Male Male | 349 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 / 1,022 | 0 / 258 | 0 / 269 | 0 / 270 |
| other Total, other adverse events | 261 / 1,022 | 50 / 258 | 101 / 269 | 14 / 270 |
| serious Total, serious adverse events | 9 / 1,022 | 3 / 258 | 1 / 269 | 1 / 270 |
Outcome results
Primary
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in the Double-Blind Period
The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Participants are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60. A negative change from Baseline indicates improvement. Mixed-effects model for repeated measures (MMRM) with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses.
Time frame: Baseline (Week 8) to Week 16
Population: Double-blind ITT Population included all participants in the double-blind safety population who had a randomization baseline assessment and at least 1 postbaseline assessment of the MADRS total score during the double-blind treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + ADT (Double-Blind) | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in the Double-Blind Period | -7.5 score on a scale | Standard Error 0.5 |
| Cariprazine + ADT (Double-Blind) | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in the Double-Blind Period | -7.7 score on a scale | Standard Error 0.5 |
p-value: 0.794895% CI: [-1.6, 1.2]Mixed Models Analysis
Primary
Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline in the Double-Blind Period
The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Patients are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60.
Time frame: Baseline (Week 8)
Population: Double-blind Intent-to-Treat (ITT) Population included all participants in the double-blind safety population who had a randomization baseline assessment and at least 1 postbaseline assessment of the MADRS total score during the double-blind treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + ADT (Double-Blind) | Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline in the Double-Blind Period | 25.2 score on a scale | Standard Deviation 6.1 |
| Cariprazine + ADT (Double-Blind) | Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline in the Double-Blind Period | 25.4 score on a scale | Standard Deviation 5.5 |
Secondary
Change From Baseline in Sheehan Disability Scale (SDS) Score in the Double-Blind Period
The Sheehan Disability Scale (SDS) is a 3-item patient-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum from 0 (no impairment) to 10 (most severe). The 3 individual scores are summed for a total possible score of 0 (unimpaired) to 30 (highly impaired). A negative change from Baseline indicates improvement. MMRM with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses.
Time frame: Baseline (Week 8) to Week 16
Population: Double-blind ITT Population included all participants in the double-blind safety population who had a randomization baseline assessment and at least 1 postbaseline assessment of the MADRS total score during the double-blind treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + ADT (Double-Blind) | Change From Baseline in Sheehan Disability Scale (SDS) Score in the Double-Blind Period | -3.1 score on a scale | Standard Error 0.5 |
| Cariprazine + ADT (Double-Blind) | Change From Baseline in Sheehan Disability Scale (SDS) Score in the Double-Blind Period | -3.7 score on a scale | Standard Error 0.5 |
p-value: 0.278495% CI: [-1.9, 0.5]Mixed Models Analysis