A Study of Aripiprazole in Patients With Major Depressive Disorder

This study has been completed.

Sponsor:

Collaborator:

Otsuka America Pharmaceutical

Information provided by:

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT00105196

First received: March 9, 2005

Last updated: April 12, 2011

Last verified: April 2011

History of Changes

Results First Received: March 27, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Diagnostic
Condition:	Major Depressive Disorder
Interventions:	Drug: Aripiprazole+ ADT Drug: Placebo+ ADT

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
Aripiprazole + ADT	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.
Placebo + ADT	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.

Participant Flow: Overall Study

	Aripiprazole + ADT	Placebo + ADT
STARTED	177	172
COMPLETED	147	149
NOT COMPLETED	30	23
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

Baseline Characteristics

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Reporting Groups

	Description
Aripiprazole + ADT	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.
Placebo + ADT	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	Total of all reporting groups

Baseline Measures

	Aripiprazole + ADT	Placebo + ADT	Total
Number of Participants [units: participants]	177	172	349
Age [units: years] Mean ± Standard Deviation	45.1 ± 10.6	45.6 ± 11.3	45.4 ± 10.9
Gender [units: participants]
Female	138	117	255
Male	39	55	94
Ethnicity (NIH/OMB) [units: participants]
Hispanic or Latino	6	6	12
Not Hispanic or Latino	168	162	330
Unknown or Not Reported	3	4	7
Race/Ethnicity, Customized [units: 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

Outcome Measures

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1. Primary:

Mean Change in the Montgomery Åsberg Depression Rating Scale (MADRS) [ Time Frame: Baseline (Week 8) and Week 14 ]

Measure Type	Primary
Measure Title	Mean Change in the Montgomery Åsberg Depression Rating Scale (MADRS)
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Aripiprazole + ADT	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.
Placebo + ADT	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.

Measured Values

	Aripiprazole + ADT	Placebo + ADT
Number of Participants Analyzed [units: participants]	174	169
Mean Change in the Montgomery Åsberg Depression Rating Scale (MADRS) [units: units on a scale] Mean ± Standard Error	-10.12 ± 0.74	-6.39 ± 0.74

Statistical Analysis 1 for Mean Change in the Montgomery Åsberg Depression Rating Scale (MADRS)

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	<0.001
Mean Difference (Final Values) ^[4]	-3.73
95% Confidence Interval	( -5.44 to -2.02 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	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.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

2. Secondary:

Mean Change in Sheehan Disability Scale (SDS) Mean Score [ Time Frame: Baseline (Week 8) and Week 14 ]

Measure Type	Secondary
Measure Title	Mean Change in Sheehan Disability Scale (SDS) Mean Score
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Aripiprazole + ADT	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.
Placebo + ADT	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.

Measured Values

	Aripiprazole + ADT	Placebo + ADT
Number of Participants Analyzed [units: participants]	160	160
Mean Change in Sheehan Disability Scale (SDS) Mean Score [units: units on a scale] Mean ± Standard Error	-1.22 ± 0.21	-0.80 ± 0.20

Statistical Analysis 1 for Mean Change in Sheehan Disability Scale (SDS) Mean Score

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	0.075
Mean Difference (Final Values) ^[4]	-0.42
95% Confidence Interval	( -0.88 to 0.04 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	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.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

3. Secondary:

Mean Change in SDS Item Score (Social Life) [ Time Frame: Baseline (Week 8) and Week 14 ]

Measure Type	Secondary
Measure Title	Mean Change in SDS Item Score (Social Life)
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Aripiprazole + ADT	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.
Placebo + ADT	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.

Measured Values

	Aripiprazole + ADT	Placebo + ADT
Number of Participants Analyzed [units: participants]	160	160
Mean Change in SDS Item Score (Social Life) [units: units on a scale] Mean ± Standard Error	-1.18 ± 0.24	-0.65 ± 0.23

Statistical Analysis 1 for Mean Change in SDS Item Score (Social Life)

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	0.052
Mean Difference (Final Values) ^[4]	-0.53
95% Confidence Interval	( -1.06 to 0.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustment for multiple comparisons was implemented for this secondary endpoint.
[4]	Other relevant estimation information:
	No text entered.

4. Secondary:

Mean Change in SDS Item Score (Family Life) [ Time Frame: Baseline (Week 8) and Week 14 ]

Measure Type	Secondary
Measure Title	Mean Change in SDS Item Score (Family Life)
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Aripiprazole + ADT	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.
Placebo + ADT	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.

Measured Values

	Aripiprazole + ADT	Placebo + ADT
Number of Participants Analyzed [units: participants]	160	160
Mean Change in SDS Item Score (Family Life) [units: units on a scale] Mean ± Standard Error	-1.39 ± 0.24	-0.82 ± 0.23

Statistical Analysis 1 for Mean Change in SDS Item Score (Family Life)

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	0.037
Mean Difference (Final Values) ^[4]	-0.57
95% Confidence Interval	( -1.10 to -0.03 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustment for multiple comparisons was implemented for this secondary endpoint.
[4]	Other relevant estimation information:
	No text entered.

5. Secondary:

Mean Change in SDS Item Score (Work/School) [ Time Frame: Baseline (Week 8) and Week 14 ]

Measure Type	Secondary
Measure Title	Mean Change in SDS Item Score (Work/School)
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Aripiprazole + ADT	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.
Placebo + ADT	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.

Measured Values

	Aripiprazole + ADT	Placebo + ADT
Number of Participants Analyzed [units: participants]	115	126
Mean Change in SDS Item Score (Work/School) [units: units on a scale] Mean ± Standard Error	-0.75 ± 0.28	-0.67 ± 0.26

Statistical Analysis 1 for Mean Change in SDS Item Score (Work/School)

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	0.792
Mean Difference (Final Values) ^[4]	-0.08
95% Confidence Interval	( -0.67 to 0.51 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustment for multiple comparisons was implemented for this secondary endpoint.
[4]	Other relevant estimation information:
	No text entered.

6. Other Pre-specified:

MADRS Response [ Time Frame: Baseline (Week 8) and Week 14 ]

Measure Type	Other Pre-specified
Measure Title	MADRS Response
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Aripiprazole + ADT	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.
Placebo + ADT	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.

Measured Values

	Aripiprazole + ADT	Placebo + ADT
Number of Participants Analyzed [units: participants]	174	169
MADRS Response [units: participants]
Responders	81	45
Nonresponders	93	124

Statistical Analysis 1 for MADRS Response

Groups ^[1]	All groups
Method ^[2]	CMH General Association Test
P Value ^[3]	<0.001
Ratio of response ^[4]	1.74
95% Confidence Interval	( 1.31 to 2.32 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustment for multiple comparisons was implemented for this secondary endpoint.
[4]	Other relevant estimation information:
	aripiprazole/placebo

7. Other Pre-specified:

Clinical Global Impression (CGI)-Improvement Response [ Time Frame: Baseline (Week 8) and Week 14 ]

Measure Type	Other Pre-specified
Measure Title	Clinical Global Impression (CGI)-Improvement Response
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Aripiprazole + ADT	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.
Placebo + ADT	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.

Measured Values

	Aripiprazole + ADT	Placebo + ADT
Number of Participants Analyzed [units: participants]	174	169
Clinical Global Impression (CGI)-Improvement Response [units: Participants]
Responders	109	74
Nonresponders	65	95

Statistical Analysis 1 for Clinical Global Impression (CGI)-Improvement Response

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	<0.001
Ratio of response ^[4]	1.43
95% Confidence Interval	( 1.17 to 1.74 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustment for multiple comparisons was implemented for this secondary endpoint.
[4]	Other relevant estimation information:
	aripiprazole/placebo

8. Other Pre-specified:

MADRS Remission [ Time Frame: Baseline (Week 8) and Week 14 ]

Measure Type	Other Pre-specified
Measure Title	MADRS Remission
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Aripiprazole + ADT	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.
Placebo + ADT	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.

Measured Values

	Aripiprazole + ADT	Placebo + ADT
Number of Participants Analyzed [units: participants]	174	169
MADRS Remission [units: participants]
Remission	64	32
No remission	110	137

Statistical Analysis 1 for MADRS Remission

Groups ^[1]	All groups
Method ^[2]	CMH General Association Test
P Value ^[3]	<0.001
Ratio of remission ^[4]	1.95
95% Confidence Interval	( 1.36 to 2.80 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustment for multiple comparisons was implemented for this secondary endpoint.
[4]	Other relevant estimation information:
	aripiprazole/placebo

Serious Adverse Events

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Other Adverse Events

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More Information

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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.

The agreement is:

	The only 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 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

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:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00105196 History of Changes
Other Study ID Numbers:	CN138-165
Study First Received:	March 9, 2005
Results First Received:	March 27, 2009
Last Updated:	April 12, 2011
Health Authority:	United States: Food and Drug Administration

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