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Trial record 12 of 1016 for:    Score | "Depressive Disorder, Major"

Safety and Efficacy of Cariprazine as an Adjunctive to Antidepressant Therapy in Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT01469377
Recruitment Status : Completed
First Posted : November 10, 2011
Results First Posted : May 1, 2018
Last Update Posted : May 1, 2018
Sponsor:
Collaborator:
Gedeon Richter Ltd.
Information provided by (Responsible Party):
Forest Laboratories

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Placebo
Drug: Cariprazine
Enrollment 819

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Cariprazine 1-2 mg Cariprazine 2-4.5 mg
Hide Arm/Group Description Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment. Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator’s discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment. Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator’s discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
Period Title: Overall Study
Started 269 274 276
Completed 234 226 210
Not Completed 35 48 66
Reason Not Completed
Protocol Deviation             7             10             10
Lost to Follow-up             3             2             5
Withdrawal of Consent             12             14             15
Adverse Event             8             18             36
Insufficient Therapeutic Response             3             4             0
Other Miscellaneous Reasons             2             0             0
Arm/Group Title Placebo Cariprazine 1-2 mg Cariprazine 2-4.5 mg Total
Hide Arm/Group Description Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment. Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator’s discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment. Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator’s discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment. Total of all reporting groups
Overall Number of Baseline Participants 266 273 273 812
Hide Baseline Analysis Population Description
The Safety Population consisted of all subjects in the Randomized Population who received at least 1 dose of double-blind investigational product.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 266 participants 273 participants 273 participants 812 participants
46.4  (11.6) 45.5  (11.9) 45.1  (11.4) 45.7  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 266 participants 273 participants 273 participants 812 participants
Female
190
  71.4%
187
  68.5%
201
  73.6%
578
  71.2%
Male
76
  28.6%
86
  31.5%
72
  26.4%
234
  28.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 266 participants 273 participants 273 participants 812 participants
White 230 234 242 706
All other races 36 39 31 106
Black or African American 32 31 24 87
Asian 1 4 4 9
American Indian or Alaska Native 2 1 1 4
Other 1 3 2 6
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 266 participants 273 participants 273 participants 812 participants
Hispanic or Latino 14 17 22 53
Not Hispanic or Latino 252 256 251 759
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 266 participants 273 participants 273 participants 812 participants
81.53  (16.19) 79.69  (16.31) 82.17  (17.37) 81.13  (16.65)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 266 participants 273 participants 273 participants 812 participants
28.93  (5.09) 28.21  (5.51) 29.05  (5.59) 28.73  (5.41)
Waist Circumference  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 266 participants 273 participants 273 participants 812 participants
94.32  (13.44) 93.36  (14.20) 94.91  (14.66) 94.20  (14.12)
1.Primary Outcome
Title Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8
Hide Description The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.
Time Frame Baseline to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population consisted of all patients in the Safety Population who had at least 1 post-baseline assessment of the MADRS total score.
Arm/Group Title Placebo Cariprazine 1-2 mg Cariprazine 2-4.5 mg
Hide Arm/Group Description:
Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator’s discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator’s discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
Overall Number of Participants Analyzed 264 273 271
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-12.5  (0.5) -13.4  (0.5) -14.6  (0.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Cariprazine 1-2 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2404
Comments p-values were from an mixed-effects model for repeated measures with 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.
Method Mixed-effect model for repeated measures
Comments p-values were adjusted for multiple comparisons using the matched parallel gate-keeping procedure.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.4 to 0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Cariprazine 2-4.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0114
Comments p-values were from an mixed-effects model for repeated measures with 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.
Method Mixed-effect model for repeated measures
Comments p-values were adjusted for multiple comparisons using the matched parallel gate-keeping procedure.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-3.7 to -0.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in the Sheehan Disability Scale (SDS) Total Score at Week 8
Hide Description The SDS measures an individual’s perception of the extent to which his or her emotional symptoms are disrupting his or her functioning in 3 domains, work/school, social life/leisure activities, and family life/home responsibilities. The participant is asked to rate the degree to which their functioning is impaired on an 11-point scale, ranging from 0 (not at all) to 10 (extremely). Scores of 0 to 3 indicate mild functional impairment, 4 to 6 indicate moderate functional impairment, and 7 to 9 indicate marked functional impairment. The scores for the 3 domains are summed into a total score that ranges from 0 (unimpaired) to 30 (highly impaired). A higher score indicates greater impairment. A negative change score indicates improvement.
Time Frame Baseline to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population consisted of all patients in the Safety Population who had at least 1 post-baseline assessment of the MADRS total score. Only participants with scores for all 3 domains were included in the analysis.
Arm/Group Title Placebo Cariprazine 1-2 mg Cariprazine 2-4.5 mg
Hide Arm/Group Description:
Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator’s discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator’s discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
Overall Number of Participants Analyzed 264 273 271
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-6.6  (0.5) -7.7  (0.5) -8.0  (0.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Cariprazine 1-2 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2404
Comments p-values were from an mixed-effects model for repeated measures with 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.
Method Mixed-effect model for repeated measures
Comments p-values were adjusted for multiple comparisons using the matched parallel gate-keeping procedure.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.5 to 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Cariprazine 2-4.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1140
Comments p-values were from an mixed-effects model for repeated measures with 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.
Method Mixed-effect model for repeated measures
Comments p-values were adjusted for multiple comparisons using the matched parallel gate-keeping procedure.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-2.8 to 0.0
Estimation Comments [Not Specified]
Time Frame Adverse Events were collected and recorded from the time the participant signs the informed consent form until 30 days after the last dose of treatment.
Adverse Event Reporting Description Safety population: All randomized participants who received at least 1 dose of treatment.
 
Arm/Group Title Placebo Cariprazine 1-2 mg Cariprazine 2-4.5 mg
Hide Arm/Group Description Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment. Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator’s discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment. Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator’s discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
All-Cause Mortality
Placebo Cariprazine 1-2 mg Cariprazine 2-4.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/266 (0.00%)   0/273 (0.00%)   0/273 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Cariprazine 1-2 mg Cariprazine 2-4.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/266 (0.38%)   0/273 (0.00%)   3/273 (1.10%) 
Cardiac disorders       
Myocardial ischemia  2  0/266 (0.00%)  0/273 (0.00%)  1/273 (0.37%) 
General disorders       
Non-cardiac chest pain  1  0/266 (0.00%)  0/273 (0.00%)  1/273 (0.37%) 
Psychiatric disorders       
Agitation  2  0/266 (0.00%)  0/273 (0.00%)  1/273 (0.37%) 
Panic attack  2  0/266 (0.00%)  0/273 (0.00%)  1/273 (0.37%) 
Depression  2  1/266 (0.38%)  0/273 (0.00%)  0/273 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  2  0/266 (0.00%)  0/273 (0.00%)  1/273 (0.37%) 
1
Term from vocabulary, MedDRA (Unspecified)
2
Term from vocabulary, MedDRA Version 16.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Cariprazine 1-2 mg Cariprazine 2-4.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   102/266 (38.35%)   121/273 (44.32%)   179/273 (65.57%) 
Gastrointestinal disorders       
Constipation  1  5/266 (1.88%)  6/273 (2.20%)  14/273 (5.13%) 
Diarrhoea  2  14/266 (5.26%)  8/273 (2.93%)  8/273 (2.93%) 
Dry mouth  2  7/266 (2.63%)  14/273 (5.13%)  10/273 (3.66%) 
Nausea  2  13/266 (4.89%)  19/273 (6.96%)  35/273 (12.82%) 
General disorders       
Fatigue  2  11/266 (4.14%)  18/273 (6.59%)  27/273 (9.89%) 
Metabolism and nutrition disorders       
Increased appetite  2  4/266 (1.50%)  5/273 (1.83%)  14/273 (5.13%) 
Nervous system disorders       
Akathisia  2  6/266 (2.26%)  18/273 (6.59%)  61/273 (22.34%) 
Dizziness  2  7/266 (2.63%)  10/273 (3.66%)  14/273 (5.13%) 
Headache  2  36/266 (13.53%)  24/273 (8.79%)  24/273 (8.79%) 
Somnolence  2  14/266 (5.26%)  24/273 (8.79%)  27/273 (9.89%) 
Tremor  2  4/266 (1.50%)  13/273 (4.76%)  21/273 (7.69%) 
Psychiatric disorders       
Insomnia  2  17/266 (6.39%)  27/273 (9.89%)  38/273 (13.92%) 
Restlessness  2  7/266 (2.63%)  22/273 (8.06%)  23/273 (8.42%) 
1
Term from vocabulary, MedDRA (Unspecified)
2
Term from vocabulary, MedDRA Version 16.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.
Results Point of Contact
Name/Title: Therapeutic Area Head
Organization: Allergan
Phone: 714-246-4500
Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT01469377     History of Changes
Other Study ID Numbers: RGH-MD-75
First Submitted: November 8, 2011
First Posted: November 10, 2011
Results First Submitted: March 29, 2018
Results First Posted: May 1, 2018
Last Update Posted: May 1, 2018