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Trial record 7 of 34 for:    "Depressive Disorder" [DISEASE] AND Behavioral | ( Map: Estonia )

Study on the Efficacy, Safety, and Tolerability of Cariprazine Relative to Placebo in Participants With Bipolar I Depression

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ClinicalTrials.gov Identifier: NCT02670551
Recruitment Status : Completed
First Posted : February 1, 2016
Results First Posted : January 30, 2019
Last Update Posted : January 30, 2019
Sponsor:
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
Conditions Bipolar Disorder
Depression
Interventions Drug: Cariprazine
Drug: Placebo
Enrollment 488
Recruitment Details  
Pre-assignment Details Total 782 participants were screened for eligibility; 488 participants randomized to receive double-blind treatment; 480 participants received at least 1 dose of double-blind treatment (Safety Population) and 474 participants had at least 1 postbaseline Montgomery-Åsberg Depression Rating Scale total score assessment (Intent-to-Treat Population).
Arm/Group Title Placebo Cariprazine 1.5 mg Cariprazine 3.0 mg
Hide Arm/Group Description Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks. Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks. Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Period Title: Overall Study
Started 163 160 165
Received Treatment (Safety Population) 158 157 165
Completed 135 134 134
Not Completed 28 26 31
Reason Not Completed
Adverse Event             4             7             9
Lack of Efficacy             2             0             3
Withdrawal of Consent             6             3             8
Lost to Follow-up             5             7             6
Protocol Violation             1             0             0
Noncompliance with study drug             3             3             2
Other Miscellaneous Reasons             2             3             3
Did Not Receive Treatment             5             3             0
Arm/Group Title Placebo Cariprazine 1.5 mg Cariprazine 3.0 mg Total
Hide Arm/Group Description Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks. Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks. Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks. Total of all reporting groups
Overall Number of Baseline Participants 163 160 165 488
Hide Baseline Analysis Population Description
All enrolled participants who were randomized to receive the double-blind treatment.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 163 participants 160 participants 165 participants 488 participants
43.9
(18 to 65)
42.6
(18 to 65)
41.9
(19 to 64)
42.8
(18 to 65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 163 participants 160 participants 165 participants 488 participants
Female
94
  57.7%
101
  63.1%
94
  57.0%
289
  59.2%
Male
69
  42.3%
59
  36.9%
71
  43.0%
199
  40.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 163 participants 160 participants 165 participants 488 participants
118
  72.4%
126
  78.8%
126
  76.4%
370
  75.8%
Black or African American Number Analyzed 163 participants 160 participants 165 participants 488 participants
39
  23.9%
29
  18.1%
37
  22.4%
105
  21.5%
Asian Number Analyzed 163 participants 160 participants 165 participants 488 participants
3
   1.8%
2
   1.3%
0
   0.0%
5
   1.0%
American Indian or Alaska Native Number Analyzed 163 participants 160 participants 165 participants 488 participants
1
   0.6%
1
   0.6%
1
   0.6%
3
   0.6%
Native Hawaiian or Other Pacific Islander Number Analyzed 163 participants 160 participants 165 participants 488 participants
2
   1.2%
0
   0.0%
0
   0.0%
2
   0.4%
Multiple Number Analyzed 163 participants 160 participants 165 participants 488 participants
0
   0.0%
2
   1.3%
1
   0.6%
3
   0.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 163 participants 160 participants 165 participants 488 participants
13
   8.0%
15
   9.4%
14
   8.5%
42
   8.6%
Not Hispanic or Latino Number Analyzed 163 participants 160 participants 165 participants 488 participants
150
  92.0%
145
  90.6%
151
  91.5%
446
  91.4%
Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 156 participants 154 participants 164 participants 474 participants
30.3  (4.5) 30.6  (4.2) 31.1  (4.8) 30.7  (4.5)
[1]
Measure Description: The Montgomery-Åsberg Depression Rating Scale is a 10-item, clinician-rated scale that evaluates the participant's depressive symptomatology during the past week. Participants were rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each of the 10 items was scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity for a total possible score of 0 (best) to 60 (worst).
[2]
Measure Analysis Population Description: Montgomery-Åsberg Depression Rating Scale (MADRS) score at Baseline was analyzed for ITT population.
Clinical Global Impressions-Severity (CGI-S) Score at Baseline   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 156 participants 154 participants 164 participants 474 participants
4.5  (0.5) 4.5  (0.5) 4.5  (0.5) 4.5  (0.5)
[1]
Measure Description: The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other participants the physician has observed. The participant was rated on a scale from 1 to 7, with 1 indicating a "normal state" and 7 indicating "among the most extremely ill participants."
[2]
Measure Analysis Population Description: Clinical Global Impressions-Severity (CGI-S) score at Baseline was analyzed for ITT population.
1.Primary Outcome
Title Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Week 6
Hide Description The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item, clinician-rated scale that evaluates the participant's depressive symptomatology during the past week. Participants were rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each of the 10 items was scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement.
Time Frame Baseline (Week 0) to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) Population included all participants from the safety population who had at least 1 postbaseline assessment of the MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title Placebo Cariprazine 1.5 mg Cariprazine 3.0 mg
Hide Arm/Group Description:
Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.
Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.
Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Overall Number of Participants Analyzed 137 135 136
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-12.6  (0.76) -15.1  (0.77) -15.6  (0.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Cariprazine 1.5 mg
Comments To control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6 for the primary and secondary efficacy parameters, the parallel gatekeeping procedure was implemented.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0331
Comments MMRM analysis was used. Fixed factors: treatment group, pooled study center, visit, treatment-group-by-visit interaction. Covariates: Baseline value, baseline value-by-visit interaction. P-value was adjusted by matched parallel gatekeeping procedure.
Method Mixed Model Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-4.6 to -0.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Cariprazine 3.0 mg
Comments To control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6 for the primary and secondary efficacy parameters, the parallel gatekeeping procedure was implemented.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0103
Comments MMRM analysis was used. Fixed factors: treatment group, pooled study center, visit, treatment-group-by-visit interaction. Covariates: Baseline value, baseline value-by-visit interaction. P-value was adjusted by matched parallel gatekeeping procedure.
Method Mixed Model Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -3.0
Confidence Interval (2-Sided) 95%
-5.1 to -0.9
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 6
Hide Description The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other participants the physician has observed. The participant was rated on a scale from 1 to 7, with 1 indicating a "normal state" and 7 indicating "among the most extremely ill participants." A negative change from Baseline indicates improvement.
Time Frame Baseline (Week 0) to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants from the safety population who had at least 1 postbaseline assessment of the MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title Placebo Cariprazine 1.5 mg Cariprazine 3.0 mg
Hide Arm/Group Description:
Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.
Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.
Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Overall Number of Participants Analyzed 137 135 136
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.3  (0.09) -1.6  (0.10) -1.6  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Cariprazine 1.5 mg
Comments To control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6 for the primary and secondary efficacy parameters, the parallel gatekeeping procedure was implemented.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0714
Comments MMRM analysis was used. Fixed factors: treatment group, pooled study center, visit, treatment-group-by-visit interaction. Covariates: Baseline value, baseline value-by-visit interaction. P-value was adjusted by matched parallel gatekeeping procedure.
Method Mixed Model Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.5 to 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Cariprazine 3.0 mg
Comments To control the overall type I error rate for multiple comparisons of 2 active doses versus placebo at Week 6 for the primary and secondary efficacy parameters, the parallel gatekeeping procedure was implemented.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0662
Comments MMRM analysis was used. Fixed factors: treatment group, pooled study center, visit, treatment-group-by-visit interaction. Covariates: Baseline value, baseline value-by-visit interaction. P-value was adjusted by matched parallel gatekeeping procedure.
Method Mixed Model Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.5 to -0.0
Estimation Comments [Not Specified]
Time Frame First dose to 30 days past last dose (Up to 80 Days)
Adverse Event Reporting Description Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
 
Arm/Group Title Placebo Cariprazine 1.5 mg Cariprazine 3.0 mg
Hide Arm/Group Description Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks. Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks. Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
All-Cause Mortality
Placebo Cariprazine 1.5 mg Cariprazine 3.0 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/158 (0.00%)   0/157 (0.00%)   0/165 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Cariprazine 1.5 mg Cariprazine 3.0 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/158 (1.27%)   2/157 (1.27%)   2/165 (1.21%) 
Blood and lymphatic system disorders       
Iron deficiency anaemia  1  0/158 (0.00%)  1/157 (0.64%)  0/165 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  1/158 (0.63%)  0/157 (0.00%)  0/165 (0.00%) 
Infections and infestations       
Chronic tonsillitis  1  1/158 (0.63%)  0/157 (0.00%)  0/165 (0.00%) 
Psychiatric disorders       
Bipolar disorder  1  0/158 (0.00%)  0/157 (0.00%)  1/165 (0.61%) 
Suicidal ideation  1  0/158 (0.00%)  0/157 (0.00%)  1/165 (0.61%) 
Respiratory, thoracic and mediastinal disorders       
Asthma  1  0/158 (0.00%)  1/157 (0.64%)  0/165 (0.00%) 
1
Term from vocabulary, MedDRA version 20.0
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 1.5 mg Cariprazine 3.0 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   43/158 (27.22%)   48/157 (30.57%)   62/165 (37.58%) 
Gastrointestinal disorders       
Nausea  1  1/158 (0.63%)  6/157 (3.82%)  15/165 (9.09%) 
Dry mouth  1  9/158 (5.70%)  6/157 (3.82%)  3/165 (1.82%) 
Nervous system disorders       
Headache  1  13/158 (8.23%)  7/157 (4.46%)  12/165 (7.27%) 
Akathisia  1  5/158 (3.16%)  10/157 (6.37%)  9/165 (5.45%) 
Dizziness  1  3/158 (1.90%)  8/157 (5.10%)  6/165 (3.64%) 
Somnolence  1  3/158 (1.90%)  8/157 (5.10%)  6/165 (3.64%) 
Sedation  1  2/158 (1.27%)  8/157 (5.10%)  5/165 (3.03%) 
Psychiatric disorders       
Insomnia  1  11/158 (6.96%)  7/157 (4.46%)  12/165 (7.27%) 
Restlessness  1  6/158 (3.80%)  2/157 (1.27%)  12/165 (7.27%) 
1
Term from vocabulary, MedDRA version 20.0
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.
A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area, Head
Organization: Allergan
Phone: 714-246-4500
EMail: clinicaltrials@allergan.com
Layout table for additonal information
Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT02670551     History of Changes
Other Study ID Numbers: RGH-MD-54
2016-000757-13 ( EudraCT Number )
First Submitted: January 28, 2016
First Posted: February 1, 2016
Results First Submitted: January 10, 2019
Results First Posted: January 30, 2019
Last Update Posted: January 30, 2019