Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, MDD, Depression
Brief summary
The objective of this study is to evaluate the long-term safety and tolerability of cariprazine as an adjunctive treatment to antidepressant therapy (ADT) in patients with Major Depressive Disorder (MDD).
Interventions
DRUGCariprazine
Cariprazine capsules 0.5 mg, 1.0 mg, and 1.5 mg; Cariprazine doses 1.5, 3.0, or 4.5 mg/day (d); patients will be titrated to a starting dose of 3.0 mg/d. Patients can stay on 3.0 mg/d or the dose can be adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability. Oral administration.
ADT such as citalopram, escitalopram, fluoxetine, sertraline, paroxetine, vilazodone, venlafaxine, desvenlafaxine, duloxetine or bupropion prescribed in accordance with its respective FDA approved package insert for each drug
Sponsors
Gedeon Richter Ltd.
Forest Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients who have provided consent prior to any study specific procedures * Meets the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for MDD * New patients must have ongoing inadequate response to protocol allowed ADTs as reported in Antidepressant Treatment Response Questionnaire (ATRQ) * For rollover patients from RGH-MD-72 \[NCT01715805\], completion of Study RGH-MD-72 (either double-blind or single-blind treatment periods) with continued ADT treatment.
Exclusion criteria
* Patients who do not meet the DSM-IV-TR criteria for MDD.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment Period | First dose of study drug to last dose of study drug in the 26-week Treatment Period and within 30 days of last dose of study drug for participants who did not participate in the 2-week Safety Follow-up Period (Up to 30 weeks) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug. |
| Number of Participants With Newly Emergent Adverse Events (NEAEs) in the Safety Follow-up Period | 2 weeks following the 26-week Treatment Period | An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A NEAE is a new AE that occurred during the 2-week Safety Follow-up Period. |
| Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters | Baseline (Week 0) to up to 26 weeks in the Treatment Period | Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator assessed the results for clinical significance. |
| Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters | Baseline (Week 0) to up to 26 weeks in the Treatment Period plus a 2-week Safety Follow-up Period (Up to 28 weeks) | Vital sign parameters included blood pressure, pulse rate, body mass index (BMI), weight, and waist circumference. The investigator assessed the results for clinical significance. |
| Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG) | Baseline (Week 0) to up to 26 weeks | A standard 12-lead ECG was performed. The investigator determined the clinical significance of the ECG findings using the central ECG interpretation laboratory report. |
| Number of Participants With Extrapyramidal Symptom (EPS)-Related TEAEs | First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks) | Extrapyramidal symptoms are drug-induced movement disorders such as dystonia, akathisia, parkinsonism, bradykinesia, tremor, and tardive dyskinesia. |
| Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | Baseline (Lead-in study Baseline for roll-over participants and prior to first dose in this study for new participants) to Week 26 in this study | The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent). The C-SSRS also captures information about the intensity of ideation, specifically the frequency, duration, controllability, deterrents, and reasons for the most severe types of ideation. Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior to 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes. |
| Number of Participants With Treatment-Emergent Ocular Events | First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks) | A TEAE is an AE that occurs or worsens after receiving study drug. Ocular events are adverse events related to the eye. |
| Change From Baseline in the Arizona Sexual Experiences Scale (ASEX) Score | Baseline (Lead-in study Baseline for roll-over participants and prior to first dose of this study for new participants) to End of Treatment (Up to Week 26) in this study | The ASEX is a participant-completed scale to evaluate overall sexual experiences over the previous 7 days consisting of 5 questions answered on a scale of 1 (best) to 6 (worst) for a total possible score of 3 to 30 (2 questions were only answered if the participant was sexually active in the past week), higher score indicates greater sexual dysfunction. There are different forms for males and females. A negative change from Baseline indicates improvement. |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
Rollover participants from Study RGH-MD-72 \[NCT01715805\] were eligible for this study if they had completed either the double-blind treatment or the continued-treatment periods. New patients were eligible if they had an ongoing inadequate response to a protocol-allowed antidepressant therapy (ADT).
Participants by arm
| Arm | Count |
|---|---|
| Cariprazine + ADT Cariprazine, flexible dose (titrated to a dose of 3.0 mg adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks. | 345 |
| Total | 345 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 49 |
| Overall Study | Did not meet eligibility criteria | 78 |
| Overall Study | Insufficient Therapeutic Response | 10 |
| Overall Study | Lost to Follow-up | 21 |
| Overall Study | Protocol Violation | 34 |
| Overall Study | Reason not Specified | 7 |
| Overall Study | Study or Site Terminated by Sponsor | 1 |
| Overall Study | Withdrawal of Consent | 33 |
Baseline characteristics
| Characteristic | Cariprazine + ADT |
|---|---|
| Age, Continuous | 46.7 years STANDARD_DEVIATION 10.5 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 75 Participants |
| Race/Ethnicity, Customized Ethnicity Non-Hispanic or Latino | 270 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 6 Participants |
| Race/Ethnicity, Customized Race Black or African American | 54 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants |
| Race/Ethnicity, Customized Race White | 280 Participants |
| Sex: Female, Male Female | 249 Participants |
| Sex: Female, Male Male | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 345 |
| other Total, other adverse events | 274 / 345 |
| serious Total, serious adverse events | 7 / 345 |
Outcome results
Primary
Change From Baseline in the Arizona Sexual Experiences Scale (ASEX) Score
The ASEX is a participant-completed scale to evaluate overall sexual experiences over the previous 7 days consisting of 5 questions answered on a scale of 1 (best) to 6 (worst) for a total possible score of 3 to 30 (2 questions were only answered if the participant was sexually active in the past week), higher score indicates greater sexual dysfunction. There are different forms for males and females. A negative change from Baseline indicates improvement.
Time frame: Baseline (Lead-in study Baseline for roll-over participants and prior to first dose of this study for new participants) to End of Treatment (Up to Week 26) in this study
Population: Participants from the Safety Population, all participants in the enrolled population who took at least 1 dose of cariprazine in this study, with data available for analysis at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cariprazine + ADT | Change From Baseline in the Arizona Sexual Experiences Scale (ASEX) Score | Baseline | 20.1 score on a scale | Standard Deviation 5.9 |
| Cariprazine + ADT | Change From Baseline in the Arizona Sexual Experiences Scale (ASEX) Score | Change from Baseline to the End of Treatment | -0.9 score on a scale | Standard Deviation 4.4 |
| Cariprazine + ADT (Male) | Change From Baseline in the Arizona Sexual Experiences Scale (ASEX) Score | Baseline | 17.2 score on a scale | Standard Deviation 5.5 |
| Cariprazine + ADT (Male) | Change From Baseline in the Arizona Sexual Experiences Scale (ASEX) Score | Change from Baseline to the End of Treatment | -0.1 score on a scale | Standard Deviation 4.6 |
Primary
Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent). The C-SSRS also captures information about the intensity of ideation, specifically the frequency, duration, controllability, deterrents, and reasons for the most severe types of ideation. Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior to 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes.
Time frame: Baseline (Lead-in study Baseline for roll-over participants and prior to first dose in this study for new participants) to Week 26 in this study
Population: Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | Ideation,Some Intent to Act,without Specific Plan | 0 participants |
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | Ideation,any Methods,without Intent to Act | 6 participants |
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | Non-specific Active Suicidal Thoughts | 3 participants |
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | Wish to be Dead | 27 participants |
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | No Suicidal Behavior | 344 participants |
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | Suicidal Behavior | 1 participants |
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | Completed Suicide | 0 participants |
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | No Suicidal Ideation | 308 participants |
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | Suicidal Ideation | 37 participants |
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | Suicidal Ideation with Specific Plan and Intent | 1 participants |
| Cariprazine + ADT | Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period | Actual Suicide Attempt | 1 participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters
Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator assessed the results for clinical significance.
Time frame: Baseline (Week 0) to up to 26 weeks in the Treatment Period
Population: Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cariprazine + ADT | Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)
A standard 12-lead ECG was performed. The investigator determined the clinical significance of the ECG findings using the central ECG interpretation laboratory report.
Time frame: Baseline (Week 0) to up to 26 weeks
Population: Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cariprazine + ADT | Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG) | 1 Participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters
Vital sign parameters included blood pressure, pulse rate, body mass index (BMI), weight, and waist circumference. The investigator assessed the results for clinical significance.
Time frame: Baseline (Week 0) to up to 26 weeks in the Treatment Period plus a 2-week Safety Follow-up Period (Up to 28 weeks)
Population: Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cariprazine + ADT | Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters | 0 Participants |
Primary
Number of Participants With Extrapyramidal Symptom (EPS)-Related TEAEs
Extrapyramidal symptoms are drug-induced movement disorders such as dystonia, akathisia, parkinsonism, bradykinesia, tremor, and tardive dyskinesia.
Time frame: First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks)
Population: Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cariprazine + ADT | Number of Participants With Extrapyramidal Symptom (EPS)-Related TEAEs | 98 Participants |
Primary
Number of Participants With Newly Emergent Adverse Events (NEAEs) in the Safety Follow-up Period
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A NEAE is a new AE that occurred during the 2-week Safety Follow-up Period.
Time frame: 2 weeks following the 26-week Treatment Period
Population: Participants in the Safety Population, all participants in the enrolled population who took at least 1 dose of cariprazine in this study, who entered the Safety Follow-up period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cariprazine + ADT | Number of Participants With Newly Emergent Adverse Events (NEAEs) in the Safety Follow-up Period | 20 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment Period
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug.
Time frame: First dose of study drug to last dose of study drug in the 26-week Treatment Period and within 30 days of last dose of study drug for participants who did not participate in the 2-week Safety Follow-up Period (Up to 30 weeks)
Population: Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cariprazine + ADT | Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment Period | 274 Participants |
Primary
Number of Participants With Treatment-Emergent Ocular Events
A TEAE is an AE that occurs or worsens after receiving study drug. Ocular events are adverse events related to the eye.
Time frame: First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks)
Population: Safety Population included all participants in the enrolled population who took at least 1 dose of cariprazine in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cariprazine + ADT | Number of Participants With Treatment-Emergent Ocular Events | 1 Participants |