A Study of Aripiprazole in Patients With Major Depressive Disorder

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00105196
• Collaborator: Otsuka America Pharmaceutical (Industry)
• Enrollment: 349
• Locations: 34
• Arms: 2
• Duration (Months): 36
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this 14 week, randomized, double-blind, placebo controlled study is to assess the safety and efficacy of aripiprazole to placebo as adjunctive treatment to an assigned open-label marketed antidepressant therapy (ADT) in patients with Major Depressive Disorder who demonstrate an incomplete response to a prospective eight week trial of the same assigned open-label marketed antidepressant therapy.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Aripiprazole+ ADT; Drug: Placebo+ ADT	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 349 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Diagnostic
• Official Title: A Study of Aripiprazole in Patients With Major Depressive Disorder
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A1	Drug: Aripiprazole+ ADT; Tablets, Oral, 2 - 20 mg variable dose once daily, 14 weeks; Other Names: Abilify
Placebo Comparator: A2	Drug: Placebo+ ADT; Tablets, Oral, 2 - 20 mg variable dose once daily, 14 weeks

Outcome Measures

Primary Outcome Measures

1. Mean Change in the Montgomery Åsberg Depression Rating Scale (MADRS) [Baseline (Week 8) and Week 14]

   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.

Secondary Outcome Measures

1. Mean Change in Sheehan Disability Scale (SDS) Mean Score [Baseline (Week 8) and Week 14]

   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.

2. Mean Change in SDS Item Score (Social Life) [Baseline (Week 8) and Week 14]

   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.

3. Mean Change in SDS Item Score (Family Life) [Baseline (Week 8) and Week 14]

   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.

4. Mean Change in SDS Item Score (Work/School) [Baseline (Week 8) and Week 14]

   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.

Other Outcome Measures

1. MADRS Response [Baseline (Week 8) and Week 14]

   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).

2. Clinical Global Impression (CGI)-Improvement Response [Baseline (Week 8) and Week 14]

   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).

3. MADRS Remission [Baseline (Week 8) and Week 14]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women, 18-65 years old who have experienced single or recurrent, non-psychotic episodes of Major Depressive Disorder, with the current episode of minimally 8 weeks in duration.

• Treatment history of an inadequate response to at least one and no more than three adequate antidepressant trials.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Of Alabama At Birmingham	Birmingham	Alabama	United States	35205
2	Sharp Mesa Vista Hospital	San Diego	California	United States	92123
3	George Washington University Medical Center	Washington	District of Columbia	United States	20037
4	Cns Clinical Research Group	Coral Springs	Florida	United States	33065
5	Medical College Of Georgia	Augusta	Georgia	United States	30912
6	Carman Research	Smyrna	Georgia	United States	30080
7	Uptown Research Institute, Llc	Chicago	Illinois	United States	60640
8	Cunningham Clinical Research, Llc	Edwardsville	Illinois	United States	62025
9	Comprehensive Neuroscience, Inc.	Hoffman Estates	Illinois	United States	60194
10	Vine Street Clinical Research Center	Springfield	Illinois	United States	62711
11	Clinical Research Institute	Witchita	Kansas	United States	67211
12	Lsu Health Sciences Center	New Orleans	Louisiana	United States	70115
13	Pharmasite Research, Inc.	Baltimore	Maryland	United States	21208
14	Summit Research Network	Farmington Hills	Michigan	United States	48336
15	Summit Research Network	Flint	Michigan	United States	48507
16	University Of Minnesota	Minneapolis	Minnesota	United States	55454
17	Regions Hospital	St. Paul	Minnesota	United States	55101
18	Radiant Research Las Vegas	Las Vegas	Nevada	United States	89146
19	Behavioral Health Center	Charlotte	North Carolina	United States	28211
20	Midwest Clinical Research Center	Dayton	Ohio	United States	45408
21	Phebe Tucker, Md	Oklahoma City	Oklahoma	United States	73104
22	Summit Research Network	Portland	Oregon	United States	97210
23	Suburban Research Associates	Media	Pennsylvania	United States	19063
24	University Of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
25	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
26	Southeast Health Consultants	Charleston	South Carolina	United States	29407
27	Usc School Of Medicine	Columbia	South Carolina	United States	29203
28	Community Clinical Research, Inc.	Austin	Texas	United States	78754
29	Radiant Research, Slc	Salt Lake City	Utah	United States	84107
30	University Of Utah School Of Medicine	Salt Lake City	Utah	United States	84132
31	University Of Virginia	Charlottesville	Virginia	United States	22903
32	Northwest Clinical Research Center	Bellevue	Washington	United States	98004
33	Northbrooke Research Center	Brown Deer	Wisconsin	United States	53223
34	Dean Foundation For Health Research & Education	Middleton	Wisconsin	United States	53562

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.
• Otsuka America Pharmaceutical

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

• Berman RM, Fava M, Thase ME, Trivedi MH, Swanink R, McQuade RD, Carson WH, Adson D, Taylor L, Hazel J, Marcus RN. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr. 2009 Apr;14(4):197-206.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT00105196
• Other Study ID Numbers: CN138-165
• First Posted: Mar 10, 2005
• Last Update Posted: Dec 2, 2013
• Last Verified: Apr 1, 2011

• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Single or recurrent; non-psychotic episode of Major Depressive Disorder
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Aripiprazole

Study Results

Participant Flow

Pre-assignment Detail	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
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

Baseline Characteristics

Arm/Group Title	Aripiprazole + ADT	Placebo + ADT	Total
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 Participants	177	172	349
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.1 (10.6)	45.6 (11.3)	45.4 (10.9)
Sex: Female, Male (Count of Participants)
Female	138 78%	117 68%	255 73.1%
Male	39 22%	55 32%	94 26.9%
Ethnicity (NIH/OMB) (Count of 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%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%	1 0.6%	1 0.3%
Asian	3 1.7%	2 1.2%	5 1.4%
Native Hawaiian or Other Pacific Islander	1 0.6%	0 0%	1 0.3%
Black or African American	14 7.9%	18 10.5%	32 9.2%
White	155 87.6%	149 86.6%	304 87.1%
Unknown or Not Reported	4 2.3%	2 1.2%	6 1.7%

Outcome Measures

1. Primary Outcome

Title	Mean Change in the Montgomery Åsberg Depression Rating Scale (MADRS)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aripiprazole + ADT	Placebo + ADT
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.
Measure Participants	174	169
Mean (Standard Error) [units on a scale]	-10.12 (0.74)	-6.39 (0.74)

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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.73
	Confidence Interval	() 95%; -5.44 to -2.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Change in Sheehan Disability Scale (SDS) Mean Score
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aripiprazole + ADT	Placebo + ADT
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.
Measure Participants	160	160
Mean (Standard Error) [units on a scale]	-1.22 (0.21)	-0.80 (0.20)

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
Statistical Test of Hypothesis	p-Value	0.075
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.42
	Confidence Interval	() 95%; -0.88 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Change in SDS Item Score (Social Life)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aripiprazole + ADT	Placebo + ADT
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.
Measure Participants	160	160
Mean (Standard Error) [units on a scale]	-1.18 (0.24)	-0.65 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole + ADT, Placebo + ADT
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.53
	Confidence Interval	() 95%; -1.06 to 0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Mean Change in SDS Item Score (Family Life)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aripiprazole + ADT	Placebo + ADT
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.
Measure Participants	160	160
Mean (Standard Error) [units on a scale]	-1.39 (0.24)	-0.82 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole + ADT, Placebo + ADT
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.57
	Confidence Interval	() 95%; -1.10 to -0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Mean Change in SDS Item Score (Work/School)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aripiprazole + ADT	Placebo + ADT
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.
Measure Participants	115	126
Mean (Standard Error) [units on a scale]	-0.75 (0.28)	-0.67 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole + ADT, Placebo + ADT
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	() 95%; -0.67 to 0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Other Pre-specified Outcome

Title	MADRS Response
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aripiprazole + ADT	Placebo + ADT
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.
Measure Participants	174	169
Responders	81 45.8%	45 26.2%
Nonresponders	93 52.5%	124 72.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole + ADT, Placebo + ADT
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
Method of Estimation	Estimation Parameter	Ratio of response
	Estimated Value	1.74
	Confidence Interval	() 95%; 1.31 to 2.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	aripiprazole/placebo

7. Other Pre-specified Outcome

Title	Clinical Global Impression (CGI)-Improvement Response
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aripiprazole + ADT	Placebo + ADT
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.
Measure Participants	174	169
Responders	109 61.6%	74 43%
Nonresponders	65 36.7%	95 55.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole + ADT, Placebo + ADT
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No adjustment for multiple comparisons was implemented for this secondary endpoint.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio of response
	Estimated Value	1.43
	Confidence Interval	() 95%; 1.17 to 1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	aripiprazole/placebo

8. Other Pre-specified Outcome

Title	MADRS Remission
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aripiprazole + ADT	Placebo + ADT
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.
Measure Participants	174	169
Remission	64 36.2%	32 18.6%
No remission	110 62.1%	137 79.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole + ADT, Placebo + ADT
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
Method of Estimation	Estimation Parameter	Ratio of remission
	Estimated Value	1.95
	Confidence Interval	() 95%; 1.36 to 2.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	aripiprazole/placebo

Adverse Events

Arm/Group Title	Aripiprazole		Placebo
Arm/Group Description
All Cause Mortality
	Aripiprazole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aripiprazole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/176 (0.6%)		1/172 (0.6%)
Psychiatric disorders
SUICIDAL IDEATION	1/176 (0.6%)		0/172 (0%)
Vascular disorders
ARTERIAL OCCLUSIVE DISEASE	0/176 (0%)		1/172 (0.6%)
Other (Not Including Serious) Adverse Events
	Aripiprazole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	107/176 (60.8%)		62/172 (36%)
Eye disorders
VISION BLURRED	13/176 (7.4%)		3/172 (1.7%)
Gastrointestinal disorders
NAUSEA	7/176 (4%)		10/172 (5.8%)
DIARRHOEA	10/176 (5.7%)		13/172 (7.6%)
CONSTIPATION	10/176 (5.7%)		6/172 (3.5%)
General disorders
FATIGUE	16/176 (9.1%)		8/172 (4.7%)
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	13/176 (7.4%)		13/172 (7.6%)
Nervous system disorders
HEADACHE	15/176 (8.5%)		14/172 (8.1%)
AKATHISIA	32/176 (18.2%)		6/172 (3.5%)
DIZZINESS	9/176 (5.1%)		5/172 (2.9%)
SOMNOLENCE	10/176 (5.7%)		1/172 (0.6%)
Psychiatric disorders
INSOMNIA	15/176 (8.5%)		9/172 (5.2%)
RESTLESSNESS	22/176 (12.5%)		6/172 (3.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.