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

This study has been completed.
Sponsor:
Collaborator:
Otsuka America Pharmaceutical
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00337571
First received: June 13, 2006
Last updated: August 3, 2010
Last verified: November 2009
History of Changes
Results First Received: June 3, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Behavioral Symptoms
Autistic Disorder
Interventions: Drug: Aripiprazole
Drug: Placebo

  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
No text entered.

Reporting Groups
  Description
Placebo No text entered.
Aripiprazole 5 mg No text entered.
Aripiprazole 10 mg No text entered.
Aripiprazole 15 mg No text entered.

Participant Flow:   Overall Study
    Placebo     Aripiprazole 5 mg     Aripiprazole 10 mg     Aripiprazole 15 mg  
STARTED     52     53     59     54  
COMPLETED     38     44     49     47  
NOT COMPLETED     14     9     10     7  
Lack of Efficacy                 3                 0                 0                 0  
Adverse Event                 4                 5                 8                 4  
Withdrawal by Subject                 2                 2                 1                 0  
Lost to Follow-up                 3                 1                 0                 1  
Poor/noncompliance                 1                 1                 1                 1  
No longer met study criteria                 1                 0                 0                 0  
High Potassium level                 0                 0                 0                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
Placebo No text entered.
Aripiprazole 5 mg No text entered.
Aripiprazole 10 mg No text entered.
Aripiprazole 15 mg No text entered.
Total Total of all reporting groups

Baseline Measures
    Placebo     Aripiprazole 5 mg     Aripiprazole 10 mg     Aripiprazole 15 mg     Total  
Number of Participants  
[units: participants]
 		  52     53     59     54     218  
Age, Customized  
[units: participants]
 		         
6 to 12 years     35     44     45     42     166  
13 to 17 years     17     9     14     12     52  
Gender  
[units: participants]
 		         
Female     4     6     9     4     23  
Male     48     47     50     50     195  
Race/Ethnicity, Customized  
[units: participants]
 		         
Asian     3     1     2     0     6  
Native Hawaiian or Other Pacific Islander     0     0     0     1     1  
Black or African American     13     13     15     9     50  
White     35     37     41     42     155  
Other     1     2     1     2     6  
Race/Ethnicity, Customized  
[units: Participants]
 		         
Hispanic/Latino     8     5     7     5     25  
Not Hispanic/Latino     44     48     52     49     193  
Weight Group  
[units: Participants]
 		         
<40 kilograms     24     35     33     34     126  
≥40 kilograms     28     18     26     20     92  
Body Mass Index  
[units: kg/m2]
Mean ± Standard Deviation 		  20.49  ± 4.777     19.91  ± 6.124     21.06  ± 6.649     20.14  ± 6.033     20.41  ± 5.933  
Height  
[units: centimeters]
Mean ± Standard Deviation 		  144.9  ± 18.82     136.5  ± 14.66     142.3  ± 17.87     139.3  ± 17.24     140.8  ± 17.38  
Weight  
[units: kilograms]
Mean ± Standard Deviation 		  45.6  ± 20.01     38.9  ± 18.26     44.8  ± 22.38     42.2  ± 22.99     42.9  ± 21.07  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Mean Change (Week 8 - Baseline) in the Autistic Behavior Checklist (ABC) Irritability Subscale Score   [ Time Frame: 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 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.

Reporting Groups
  Description
Placebo No text entered.
Aripiprazole 5 mg No text entered.
Aripiprazole 10 mg No text entered.
Aripiprazole 15 mg No text entered.

Measured Values
    Placebo     Aripiprazole 5 mg     Aripiprazole 10 mg     Aripiprazole 15 mg  
Number of Participants Analyzed  
[units: participants]
 		  49     52     59     53  
Mean Change (Week 8 - Baseline) in the Autistic Behavior Checklist (ABC) Irritability Subscale Score  
[units: units on a scale]
Mean ± Standard Error 		  -8.4  ± 1.39     -12.4  ± 1.36     -13.2  ± 1.25     -14.4  ± 1.31  

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   [ Time Frame: 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 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.

Reporting Groups
  Description
Placebo No text entered.
Aripiprazole 5 mg No text entered.
Aripiprazole 10 mg No text entered.
Aripiprazole 15 mg No text entered.

Measured Values
    Placebo     Aripiprazole 5 mg     Aripiprazole 10 mg     Aripiprazole 15 mg  
Number of Participants Analyzed  
[units: participants]
 		  49     52     59     53  
Mean Clinical Global Impressions Improvement Scale (CGI-I) Score  
[units: units on a scale]
Mean ± Standard Error 		  3.3  ± 0.18     2.6  ± 0.17     2.5  ± 0.16     2.5  ± 0.17  

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



3.  Secondary:   Number of Participants With Response at Week 8   [ Time Frame: 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 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.

Reporting Groups
  Description
Placebo No text entered.
Aripiprazole 5 mg No text entered.
Aripiprazole 10 mg No text entered.
Aripiprazole 15 mg No text entered.

Measured Values
    Placebo     Aripiprazole 5 mg     Aripiprazole 10 mg     Aripiprazole 15 mg  
Number of Participants Analyzed  
[units: participants]
 		  49     52     59     53  
Number of Participants With Response at Week 8  
[units: Participants]
 		  17     29     29     28  

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)   [ Time Frame: 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 decreased 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 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.

Reporting Groups
  Description
Placebo No text entered.
Aripiprazole 5 mg No text entered.
Aripiprazole 10 mg No text entered.
Aripiprazole 15 mg No text entered.

Measured Values
    Placebo     Aripiprazole 5 mg     Aripiprazole 10 mg     Aripiprazole 15 mg  
Number of Participants Analyzed  
[units: participants]
 		  44     46     54     48  
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 		  -1.7  ± 0.50     -2.6  ± 0.50     -2.4  ± 0.44     -3.2  ± 0.47  

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   [ Time Frame: 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 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.

Reporting Groups
  Description
Placebo No text entered.
Aripiprazole 5 mg No text entered.
Aripiprazole 10 mg No text entered.
Aripiprazole 15 mg No text entered.

Measured Values
    Placebo     Aripiprazole 5 mg     Aripiprazole 10 mg     Aripiprazole 15 mg  
Number of Participants Analyzed  
[units: participants]
 		  49     52     59     53  
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores  
[units: units on a scale]
Mean ± Standard Error 		       
ABC Hyperactivity Subscale Score     -7.7  ± 1.67     -14.0  ± 1.64     -13.3  ± 1.50     -16.3  ± 1.59  
ABC Stereotypy Subscale Score     -1.8  ± 0.69     -4.5  ± 0.68     -4.2  ± 0.63     -4.5  ± 0.66  
ABC Inappropriate Speech Subscale Score     -1.1  ± 0.46     -2.0  ± 0.45     -1.8  ± 0.41     -2.3  ± 0.43  
ABC Social Withdrawal Subscale Score     -5.2  ± 1.16     -5.8  ± 1.15     -4.9  ± 1.06     -7.9  ± 1.11  

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)   [ Time Frame: 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 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.

Reporting Groups
  Description
Placebo No text entered.
Aripiprazole 5 mg No text entered.
Aripiprazole 10 mg No text entered.
Aripiprazole 15 mg No text entered.

Measured Values
    Placebo     Aripiprazole 5 mg     Aripiprazole 10 mg     Aripiprazole 15 mg  
Number of Participants Analyzed  
[units: participants]
 		  41     44     52     44  
Mean Change (Week 8 - Baseline) in CGI-Severity (CGI-S)  
[units: units on a scale]
Mean ± Standard Error 		  -0.6  ± 0.16     -0.9  ± 0.15     -1.0  ± 0.13     -1.1  ± 0.15  

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



7.  Secondary:   Summary of Safety   [ Time Frame: continuously 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 continuously 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 patients in the placebo group (no longer met study criteria), and 1 participant in the 5-mg group who withdrew consent.

Reporting Groups
  Description
Placebo No text entered.
Aripiprazole 5 mg No text entered.
Aripiprazole 10 mg No text entered.
Aripiprazole 15 mg No text entered.

Measured Values
    Placebo     Aripiprazole 5 mg     Aripiprazole 10 mg     Aripiprazole 15 mg  
Number of Participants Analyzed  
[units: participants]
 		  51     52     59     54  
Summary of Safety  
[units: participants]
 		       
Deaths     0     0     0     0  
Treatment-emergent SAEs     0     1     1     0  
AEs leading to discontinuation of study medication     4     5     8     4  
Treatment-emergent AEs overall     37     46     53     46  
Treatment-emergent AEs related to study medication     22     37     50     39  
Treatment-emergent extrapyramidal symptom AEs     6     12     13     12  

No statistical analysis provided for Summary of Safety



8.  Secondary:   Change From Baseline in Body Weight   [ Time Frame: 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 3 patients in the placebo group (1 no longer met study criteria, 2 did not have measurement at baseline and Week 8), and 1 participant in the 5-mg group who withdrew consent. Data set is LOCF.

Reporting Groups
  Description
Placebo No text entered.
Aripiprazole 5 mg No text entered.
Aripiprazole 10 mg No text entered.
Aripiprazole 15 mg No text entered.

Measured Values
    Placebo     Aripiprazole 5 mg     Aripiprazole 10 mg     Aripiprazole 15 mg  
Number of Participants Analyzed  
[units: participants]
 		  49     52     59     53  
Change From Baseline in Body Weight  
[units: kilograms]
Mean ± Standard Error 		  0.3  ± 0.32     1.3  ± 0.31     1.3  ± 0.29     1.5  ± 0.30  

No statistical analysis provided for Change From Baseline in Body Weight




  Serious Adverse Events
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  Other Adverse Events
  Show Other Adverse Events


  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:
unchecked 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.
unchecked 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.


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:


Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00337571     History of Changes
Other Study ID Numbers: CN138-179
Study First Received: June 13, 2006
Results First Received: June 3, 2009
Last Updated: August 3, 2010
Health Authority: United States: Food and Drug Administration