Study of Aripiprazole in the Treatment of Children and Adolescents With Autistic Disorder (AD) - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment
Condition:	Autistic Disorder
Interventions:	Drug: Aripiprazole Drug: Placebo

	Placebo	Aripiprazole
STARTED	51	47
COMPLETED	36	39
NOT COMPLETED	15	8
Lack of Efficacy	6	1
Adverse Event	3	5
Withdrawal by Subject	2	1
Lost to Follow-up	4	1

	Placebo	Aripiprazole	Total
Number of Participants [units: participants]	51	47	98
Age, Customized [units: participants]
6 to 12 years	46	37	83
13 to 17 years	5	10	15
Gender [units: participants]
Female	7	5	12
Male	44	42	86
Race/Ethnicity, Customized [units: participants]
Asian	0	2	2
Native Hawaiian or Other Pacific Islander	0	1	1
Black or African American	7	11	18
White	41	32	73
Other	3	1	4
Race/Ethnicity, Customized [units: participants]
Hispanic/Latino	8	6	14
Not Hispanic/Latino	43	41	84
Weight Group [units: Participants]
<40 kilograms	32	26	58
≥40 kilograms	19	21	40
Body Mass Index [units: kg/cm2] Mean ± Standard Deviation	19.96 ± 5.392	21.08 ± 5.394	20.50 ± 5.395
Height [units: centimeters] Mean ± Standard Deviation	138.6 ± 14.7	140.9 ± 18.80	139.7 ± 16.74
Weight [units: kilograms] Mean ± Standard Deviation	40.6 ± 18.92	43.9 ± 19.15	42.2 ± 19.01

Outcome Measures

1. Primary:

Mean Change (Week 8 - Baseline) in the Autistic Behavior Checklist (ABC) Irritability Subscale Score [ Week 8 ]

Measure Type	Primary
Measure Title	Mean Change (Week 8 - Baseline) in the Autistic Behavior Checklist (ABC) Irritability Subscale Score
Measure Description	The ABC is a 58-item informant-based assessment of problem behaviors in children/adolescents with mental retardation. Items are rated on a 4-point scale (0=no problem, 3=severe problem), and resolve into 5 domain subscales. A decrease in score indicates improvement.
Time Frame	Week 8
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.
Efficacy population=all randomized participants minus 2 patients in the placebo group (1 lost to follow-up, 1 withdrew consent) and 1 participant in the aripiprazole group who discontinued due to AE on Day 2. Data set is LOCF.

Reporting Groups

	Description
Placebo	oral placebo once daily (QD)
Aripiprazole	oral aripiprazole 2 to 15 mg QD

Measured Values

	Placebo	Aripiprazole
Number of Participants Analyzed [units: participants]	49	46
Mean Change (Week 8 - Baseline) in the Autistic Behavior Checklist (ABC) Irritability Subscale Score [units: units on a scale] Mean ± Standard Error	-5.0 ± 1.43	-12.9 ± 1.44

No statistical analysis provided for Mean Change (Week 8 - Baseline) in the Autistic Behavior Checklist (ABC) Irritability Subscale Score

2. Secondary:

Mean Clinical Global Impressions Improvement Scale (CGI-I) Score [ Week 8 ]

Measure Type	Secondary
Measure Title	Mean Clinical Global Impressions Improvement Scale (CGI-I) Score
Measure Description	The CGI scale is a clinician-rated global assessment of a patient’s improvement over time. Baseline assessment rated a patient’s condition on a 7-point scale (1=no symptoms, 7=very severe symptoms). Subsequent assessed improvement relative to baseline symptoms on a 7-point CGI-I item scale (1=very much improved, 7=very much worse).
Time Frame	Week 8
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.
Efficacy population=all randomized participants minus 2 patients in the placebo group (1 lost to follow-up, 1 withdrew consent) and 1 participant in the aripiprazole group who discontinued due to AE on Day 2. Data set is LOCF.

Reporting Groups

	Description
Placebo	oral placebo once daily (QD)
Aripiprazole	oral aripiprazole 2 to 15 mg QD

Measured Values

	Placebo	Aripiprazole
Number of Participants Analyzed [units: participants]	49	46
Mean Clinical Global Impressions Improvement Scale (CGI-I) Score [units: units on a scale] Mean ± Standard Error	3.6 ± 0.18	2.2 ± 0.18

No statistical analysis provided for Mean Clinical Global Impressions Improvement Scale (CGI-I) Score

3. Secondary:

Number of Participants With Response at Week 8 [ Week 8 ]

Measure Type	Secondary
Measure Title	Number of Participants With Response at Week 8
Measure Description	Response defined as a ≥ 25% reduction from baseline to endpoint in the ABC Irritability Subscale score and a CGI-I score of 1 or 2 at endpoint
Time Frame	Week 8
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.
Efficacy population=all randomized participants minus 2 patients in the placebo group (1 lost to follow-up, 1 withdrew consent) and 1 participant in the aripiprazole group who discontinued due to AE on Day 2. Data set is LOCF.

Reporting Groups

	Description
Placebo	oral placebo once daily (QD)
Aripiprazole	oral aripiprazole 2 to 15 mg QD

Measured Values

	Placebo	Aripiprazole
Number of Participants Analyzed [units: participants]	49	46
Number of Participants With Response at Week 8 [units: participant]	7	24

No statistical analysis provided for Number of Participants With Response at Week 8

4. Secondary:

Mean Change (Week 8 – Baseline) in the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS; Compulsion Scale Only) [ Week 8 ]

Measure Type	Secondary
Measure Title	Mean Change (Week 8 – Baseline) in the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS; Compulsion Scale Only)
Measure Description	CY-BOCS=10-item assessment of obsessive-compulsive symptoms in patients <18 years. 5 items pertaining to compulsions rate symptoms (time spent, interference with functioning, distress, resistance, control) on a 5-point scale (0=no symptoms/minimum severity, 4=extreme symptoms/maximum severity). A decrease in value indicates improvement.
Time Frame	Week 8
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.
Efficacy population=all randomized participants minus 2 patients in the placebo group (1 lost to follow-up, 1 withdrew consent) and 1 participant in the aripiprazole group who discontinued due to AE on Day 2. Data set is LOCF.

Reporting Groups

	Description
Placebo	oral placebo once daily (QD)
Aripiprazole	oral aripiprazole 2 to 15 mg QD

Measured Values

	Placebo	Aripiprazole
Number of Participants Analyzed [units: participants]	44	43
Mean Change (Week 8 – Baseline) in the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS; Compulsion Scale Only) [units: units on a scale] Mean ± Standard Error	-0.8 ± 0.52	-3.8 ± 0.50

No statistical analysis provided for Mean Change (Week 8 – Baseline) in the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS; Compulsion Scale Only)

5. Secondary:

Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores [ Week 8 ]

Measure Type	Secondary
Measure Title	Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores
Measure Description	Mean change (Week 8 - baseline) in the other ABC subscale scores (lethargy/social withdrawal; stereotypic behavior; hyperactivity/ noncompliance; inappropriate speech). A decrease in value indicates improvement
Time Frame	Week 8
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.
Efficacy population=all randomized participants minus 2 patients in the placebo group (1 lost to follow-up, 1 withdrew consent) and 1 participant in the aripiprazole group who discontinued due to AE on Day 2. Data set is LOCF.

Reporting Groups

	Description
Placebo	oral placebo once daily (QD)
Aripiprazole	oral aripiprazole 2 to 15 mg QD

Measured Values

	Placebo	Aripiprazole
Number of Participants Analyzed [units: participants]	49	46
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores [units: units of a scale] Mean ± Standard Error
ABC Hyperactivity Subscale Score	-2.8 ± 1.5	-12.7 ± 1.52
ABC Stereotypy Subscale Score	-2.0 ± 0.62	-4.8 ± 0.63
ABC Inappropriate Speech Subscale Score	-0.4 ± 0.39	-2.5 ± 0.39
ABC Social Withdrawal Subscale Score	-6.2 ± 1.13	-7.9 ± 1.15

No statistical analysis provided for Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores

6. Secondary:

Mean Change (Week 8 - Baseline) in CGI-Severity (CGI-S) [ Week 8 ]

Measure Type	Secondary
Measure Title	Mean Change (Week 8 - Baseline) in CGI-Severity (CGI-S)
Measure Description	A CGI-S assessment (a 7-point scale to evaluate the severity of symptoms) was performed at baseline (1=no symptoms; 7=very severe symptoms). The patient’s improvement relative to the symptoms at baseline on were assessed on a 7-point CGI-I (1=very much improved; 7=very much worse). A decrease in value indicates improvement.
Time Frame	Week 8
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.
Efficacy population=all randomized participants minus 2 patients in the placebo group (1 lost to follow-up, 1 withdrew consent) and 1 participant in the aripiprazole group who discontinued due to AE on Day 2. Data set is LOCF.

Reporting Groups

	Description
Placebo	oral placebo once daily (QD)
Aripiprazole	oral aripiprazole 2 to 15 mg QD

Measured Values

	Placebo	Aripiprazole
Number of Participants Analyzed [units: participants]	40	40
Mean Change (Week 8 - Baseline) in CGI-Severity (CGI-S) [units: units on a scale] Mean ± Standard Deviation	-0.4 ± 0.15	-1.2 ± 0.14

No statistical analysis provided for Mean Change (Week 8 - Baseline) in CGI-Severity (CGI-S)

7. Secondary:

Summary of Safety [ continuous throughout the study ]

Measure Type	Secondary
Measure Title	Summary of Safety
Measure Description	Deaths, Adverse Events (AEs), Serious AEs (SAEs), Treatment-Emergent AEs and AEs leading to discontinuation
Time Frame	continuous throughout the study
Safety Issue	Yes

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.
Safety population=all randomized participants minus 1 patient in the placebo group lost to follow-up. Data set is LOCF.

Reporting Groups

	Description
Placebo	oral placebo once daily (QD)
Aripiprazole	oral aripiprazole 2 to 15 mg QD

Measured Values

	Placebo	Aripiprazole
Number of Participants Analyzed [units: participants]	50	47
Summary of Safety [units: participants]
Deaths	0	0
Treatment-emergent SAEs	0	0
AEs leading to discontinuation	3	5
Treatment-emergent AEs overall	36	43
Treatment-emergent AEs realted to study drug	25	39
Treatment-emergent extrapyramidal symptom AEs	4	7

No statistical analysis provided for Summary of Safety

8. Secondary:

Change From Baseline in Body Weight [ Week 8 ]

Measure Type	Secondary
Measure Title	Change From Baseline in Body Weight
Measure Description	Adjusted mean change (Week 8 - baseline) in body weight
Time Frame	Week 8
Safety Issue	Yes

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.
Safety population=all randomized participants minus 1 patient in the placebo group lost to follow-up. Includes all participants with weight measurement at baseline and timepoint. Data set is LOCF.

Reporting Groups

	Description
Placebo	oral placebo once daily (QD)
Aripiprazole	oral aripiprazole 2 to 15 mg QD

Measured Values

	Placebo	Aripiprazole
Number of Participants Analyzed [units: participants]	49	45
Change From Baseline in Body Weight [units: kilograms] Mean ± Standard Error	0.8 ± 0.29	2.0 ± 0.30

No statistical analysis provided for Change From Baseline in Body Weight

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
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Results Point of Contact:

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

No publications provided

Responsible Party:	Bristol-Myers Squibb ( Study Director )
Study ID Numbers:	CN138-178
Study First Received:	May 31, 2006
Results First Received:	June 3, 2009
Last Updated:	June 3, 2009
ClinicalTrials.gov Identifier:	NCT00332241 History of Changes
Health Authority:	United States: Food and Drug Administration