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A Study of Aripiprazole in Patients With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT00105196
Recruitment Status : Completed
First Posted : March 10, 2005
Results First Posted : May 18, 2009
Last Update Posted : December 2, 2013
Sponsor:
Collaborator:
Otsuka America Pharmaceutical
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Diagnostic
Condition Major Depressive Disorder
Interventions Drug: Aripiprazole+ ADT
Drug: Placebo+ ADT
Enrollment 349

Recruitment Details  
Pre-assignment Details After initial screening period (7-28 days), subjects enrolled into an 8-wk prospective treatment phase (single-blind placebo plus an investigator-assigned, open-label, marketed antidepressant therapy [ADT]). Patients who met criteria for incomplete response at the end of this phase were randomized into the 6-wk double-blind phase in a 1:1 ratio.
Arm/Group Title Aripiprazole + ADT Placebo + ADT
Hide Arm/Group Description Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward. Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Period Title: Overall Study
Started 177 172
Completed 147 149
Not Completed 30 23
Reason Not Completed
Lack of Efficacy             2             3
Adverse Event             11             3
Withdrawal by Subject             6             6
Lost to Follow-up             3             2
Poor/noncompliance             3             4
Protocol Violation             5             2
pending surgery             0             1
marijuana use             0             1
Subject became unblinded             0             1
Arm/Group Title Aripiprazole + ADT Placebo + ADT Total
Hide Arm/Group Description Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward. Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward. Total of all reporting groups
Overall Number of Baseline Participants 177 172 349
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 177 participants 172 participants 349 participants
45.1  (10.6) 45.6  (11.3) 45.4  (10.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 172 participants 349 participants
Female
138
  78.0%
117
  68.0%
255
  73.1%
Male
39
  22.0%
55
  32.0%
94
  26.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 172 participants 349 participants
Hispanic or Latino
6
   3.4%
6
   3.5%
12
   3.4%
Not Hispanic or Latino
168
  94.9%
162
  94.2%
330
  94.6%
Unknown or Not Reported
3
   1.7%
4
   2.3%
7
   2.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 177 participants 172 participants 349 participants
American Indian or Alaska Native 0 1 1
Asian 3 2 5
Native Hawaiian or Other Pacific Islander 1 0 1
Black or African American 14 18 32
White 155 149 304
Unknown or Not Reported 4 2 6
1.Primary Outcome
Title Mean Change in the Montgomery Åsberg Depression Rating Scale (MADRS)
Hide Description Mean change from Week 8 (baseline) to Week 14 in MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score – baseline score. A negative change score indicates improvement.
Time Frame Baseline (Week 8) and Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole + ADT Placebo + ADT
Hide Arm/Group Description:
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Overall Number of Participants Analyzed 174 169
Mean (Standard Error)
Unit of Measure: units on a scale
-10.12  (0.74) -6.39  (0.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole + ADT, Placebo + ADT
Comments The sample size for the study was based on the primary outcome measure. The study was powered at 90% to detect a treatment difference between adjunctive aripiprazole and adjunctive placebo of 3.75, assuming a standard deviation of 10.5 and a two-sided alpha level of 0.05. The null-hypothesis was the lack of a treatment difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.73
Confidence Interval 95%
-5.44 to -2.02
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change in Sheehan Disability Scale (SDS) Mean Score
Hide Description Mean change from Week 8 (baseline) to Week 14 in SDS Mean Score, a 3-item, ordinal scale (0=unimpaired; 30=highly impaired). Change from baseline=postbaseline score – baseline score. A negative change score indicates improvement.
Time Frame Baseline (Week 8) and Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole + ADT Placebo + ADT
Hide Arm/Group Description:
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Overall Number of Participants Analyzed 160 160
Mean (Standard Error)
Unit of Measure: units on a scale
-1.22  (0.21) -0.80  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole + ADT, Placebo + ADT
Comments To protect the overall (primary and key secondary efficacy analysis) alpha level of 0.05, for this key secondary endpoint a hierarchical testing procedure was followed such that formal testing would take place conditional on the primary efficacy analysis showing a statistically significant difference.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.42
Confidence Interval 95%
-0.88 to 0.04
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change in SDS Item Score (Social Life)
Hide Description Mean change from Week 8 (baseline) to Week 14 in SDS Social Life Item Score, 1 item from a 3-item, ordinal scale (0=unimpaired; 10=highly impaired). Change from baseline=postbaseline score – baseline score. A negative change score indicates improvement.
Time Frame Baseline (Week 8) and Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole + ADT Placebo + ADT
Hide Arm/Group Description:
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Overall Number of Participants Analyzed 160 160
Mean (Standard Error)
Unit of Measure: units on a scale
-1.18  (0.24) -0.65  (0.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole + ADT, Placebo + ADT
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.052
Comments No adjustment for multiple comparisons was implemented for this secondary endpoint.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.53
Confidence Interval 95%
-1.06 to 0.00
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change in SDS Item Score (Family Life)
Hide Description Mean change from Week 8 (Baseline) to Week 14 in SDS Family Life Item Score, 1 item from a 3-item, ordinal scale (0=unimpaired; 10=highly impaired). Change from baseline=postbaseline score – baseline score. A negative change score indicates improvement.
Time Frame Baseline (Week 8) and Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole + ADT Placebo + ADT
Hide Arm/Group Description:
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Overall Number of Participants Analyzed 160 160
Mean (Standard Error)
Unit of Measure: units on a scale
-1.39  (0.24) -0.82  (0.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole + ADT, Placebo + ADT
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments No adjustment for multiple comparisons was implemented for this secondary endpoint.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.57
Confidence Interval 95%
-1.10 to -0.03
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change in SDS Item Score (Work/School)
Hide Description Mean change from Week 8 (baseline) to Week 14 in SDS Work/School Item Score, 1 item from a 3-item, ordinal scale (0=unimpaired; 10=highly impaired). Change from baseline=postbaseline score – baseline score. A negative change score indicates improvement.
Time Frame Baseline (Week 8) and Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole + ADT Placebo + ADT
Hide Arm/Group Description:
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Overall Number of Participants Analyzed 115 126
Mean (Standard Error)
Unit of Measure: units on a scale
-0.75  (0.28) -0.67  (0.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole + ADT, Placebo + ADT
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.792
Comments No adjustment for multiple comparisons was implemented for this secondary endpoint.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.08
Confidence Interval 95%
-0.67 to 0.51
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title MADRS Response
Hide Description Number of subjects with a ≥50 percent reduction from Week 8 (baseline) in MADRS Total Score, a 10-item, ordinal rating scale to assess the severity of depressive symptoms (0=no symptoms; 60=most severe symptoms).
Time Frame Baseline (Week 8) and Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole + ADT Placebo + ADT
Hide Arm/Group Description:
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Overall Number of Participants Analyzed 174 169
Measure Type: Number
Unit of Measure: participants
Responders 81 45
Nonresponders 93 124
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole + ADT, Placebo + ADT
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No adjustment for multiple comparisons was implemented for this secondary endpoint.
Method CMH General Association Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of response
Estimated Value 1.74
Confidence Interval 95%
1.31 to 2.32
Estimation Comments aripiprazole/placebo
7.Other Pre-specified Outcome
Title Clinical Global Impression (CGI)-Improvement Response
Hide Description Number of subjects with response relative to Week 8 (baseline). Response defined as score of 1 (very much improved) or 2 (much improved) on a 7-point, ordinal scale (1=very much improved; 7=very much worse).
Time Frame Baseline (Week 8) and Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole + ADT Placebo + ADT
Hide Arm/Group Description:
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Overall Number of Participants Analyzed 174 169
Measure Type: Number
Unit of Measure: Participants
Responders 109 74
Nonresponders 65 95
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole + ADT, Placebo + ADT
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No adjustment for multiple comparisons was implemented for this secondary endpoint.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of response
Estimated Value 1.43
Confidence Interval 95%
1.17 to 1.74
Estimation Comments aripiprazole/placebo
8.Other Pre-specified Outcome
Title MADRS Remission
Hide Description Number of subjects in remission. Remission defined as as MADRS Total Score of <10 at 14 weeks, and a reduction of ≥50 percent from Week 8 (baseline) in MADRS, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms).
Time Frame Baseline (Week 8) and Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole + ADT Placebo + ADT
Hide Arm/Group Description:
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (aripiprazole). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Subjects with a recorded baseline value at Week 8 and at least one recorded value on randomized study drug (placebo). Missing baseline values were not imputed. Missing values on study drug were imputed using LOCF. Baseline values were not carried forward.
Overall Number of Participants Analyzed 174 169
Measure Type: Number
Unit of Measure: participants
Remission 64 32
No remission 110 137
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole + ADT, Placebo + ADT
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No adjustment for multiple comparisons was implemented for this secondary endpoint.
Method CMH General Association Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of remission
Estimated Value 1.95
Confidence Interval 95%
1.36 to 2.80
Estimation Comments aripiprazole/placebo
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Aripiprazole Placebo
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Aripiprazole Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Aripiprazole Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/176 (0.57%)   1/172 (0.58%) 
Psychiatric disorders     
SUICIDAL IDEATION  1  1/176 (0.57%)  0/172 (0.00%) 
Vascular disorders     
ARTERIAL OCCLUSIVE DISEASE  1  0/176 (0.00%)  1/172 (0.58%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aripiprazole Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   107/176 (60.80%)   62/172 (36.05%) 
Eye disorders     
VISION BLURRED  1  13/176 (7.39%)  3/172 (1.74%) 
Gastrointestinal disorders     
NAUSEA  1  7/176 (3.98%)  10/172 (5.81%) 
DIARRHOEA  1  10/176 (5.68%)  13/172 (7.56%) 
CONSTIPATION  1  10/176 (5.68%)  6/172 (3.49%) 
General disorders     
FATIGUE  1  16/176 (9.09%)  8/172 (4.65%) 
Infections and infestations     
UPPER RESPIRATORY TRACT INFECTION  1  13/176 (7.39%)  13/172 (7.56%) 
Nervous system disorders     
HEADACHE  1  15/176 (8.52%)  14/172 (8.14%) 
AKATHISIA  1  32/176 (18.18%)  6/172 (3.49%) 
DIZZINESS  1  9/176 (5.11%)  5/172 (2.91%) 
SOMNOLENCE  1  10/176 (5.68%)  1/172 (0.58%) 
Psychiatric disorders     
INSOMNIA  1  15/176 (8.52%)  9/172 (5.23%) 
RESTLESSNESS  1  22/176 (12.50%)  6/172 (3.49%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11
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.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial’s primary publication.
Results Point of Contact
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT00105196     History of Changes
Other Study ID Numbers: CN138-165
First Submitted: March 9, 2005
First Posted: March 10, 2005
Results First Submitted: March 27, 2009
Results First Posted: May 18, 2009
Last Update Posted: December 2, 2013