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

This study has been completed.
Sponsor:
Collaborator:
Otsuka America Pharmaceutical
Information provided by:
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00365859
First received: August 15, 2006
Last updated: November 7, 2013
Last verified: June 2010
Results First Received: December 17, 2009  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Autistic Disorder
Behavioral Symptoms
Intervention: Drug: Aripiprazole

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
109 participants were enrolled in the De Novo arm, 70 in the Rollover Placebo arm, and 174 in the Rollover Aripiprazole arm. 23 participants in the De Novo arm were considered "baseline failures," and did not enter the treatment phase.

Reporting Groups
  Description
De Novo De novo participants (those who did not participate in protocol (CN138-178 [NCT00332241] or CN138-179 [NCT00337571]) assigned to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.
Rollover Placebo Participants who completed participation in protocol (CN138-178 [NCT00332241] or CN138-179 [NCT00337571]) on placebo treatment and continued to meet all of the inclusion criteria and none of the exclusion criteria. Assigned in this study to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.
Rollover Aripiprazole Participants who completed participation in protocol CN138-178 [NCT00332241] or CN138-179 [NCT00337571] on aripiprazole treatment and continued to meet all of the inclusion criteria and none of the exclusion criteria. Assigned in this study to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.
Total No text entered.

Participant Flow:   Overall Study
    De Novo     Rollover Placebo     Rollover Aripiprazole     Total  
STARTED     86     70     174     330  
Safety Population     86     70     174     330  
Efficacy Population     84 [1]   69 [2]   169 [3]   322  
COMPLETED     55     37     107     199  
NOT COMPLETED     31     33     67     131  
[1] 1 patient was lost to follow-up and 1 not included due to moderate sedation (total=2)
[2] 1 not included due to increased alanine aminotransferase (ALT) prior to treatment with aripiprazole
[3] 3 lost to follow-up, 1 not included due to mild increased appetite, 1 to family emergency (total=5)



  Baseline Characteristics
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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.
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Reporting Groups
  Description
De Novo As previously described in Participant Flow
Rollover Placebo As previously described in Participant Flow
Rollover Aripiprazole As previously described in Participant Flow
Total Total of all reporting groups

Baseline Measures
    De Novo     Rollover Placebo     Rollover Aripiprazole     Total  
Number of Participants  
[units: participants]
  86     70     174     330  
Age, Customized  
[units: participants]
       
6 to 12 years     69     56     138     263  
13 to 17 years     17     14     36     67  
Age  
[units: years]
Mean ± Standard Deviation
  9.7  ± 3.13     9.6  ± 2.95     9.5  ± 3.00     9.6  ± 3.02  
Gender  
[units: participants]
       
Female     16     8     19     43  
Male     70     62     155     287  



  Outcome Measures
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1.  Primary:   Number of Participants With Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (AEs), Deaths, AEs Leading to Discontinuation, Extra Pyramidal Syndrome (EPS)-Related AEs   [ Time Frame: From Screening (up to 42 days prior to treatment start) through Week 52 (end of study) for SAEs; from Week 0 (Baseline) through Week 52 (End of Study) for AEs ]

2.  Primary:   Mean Change From Baseline in Total Simpson-Angus Scale (SAS) At Week 8, Week 26, and Week 52   [ Time Frame: Baseline, Week 8, Week 26, Week 52 ]

3.  Primary:   Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) At Week 8, Week 26, and Week 52   [ Time Frame: Baseline, Week 8, Week 26, Week 52 ]

4.  Primary:   Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Week 8, Week 26, Week 52, and Endpoint   [ Time Frame: Baseline, Week 8, Week 26, Week 52 ]

5.  Primary:   Number of Participants With Potentially Clinically Relevant Laboratory Metabolic Abnormalities   [ Time Frame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52 ]

6.  Primary:   Number of Participants With Potentially Clinically Relevant Laboratory Hematology Abnormalities   [ Time Frame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52 ]

7.  Primary:   Number of Participants With Potentially Clinically Relevant Laboratory Chemistry Abnormalities   [ Time Frame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52 ]

8.  Primary:   Number of Participants With Potentially Clinically Relevant Eletrocardiograph (ECG) Abnormalities   [ Time Frame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52 ]

9.  Primary:   Number of Potentially Clinically Relevant Vital Sign Abnormalities   [ Time Frame: At screening (up to 42 days prior to treatment start), Week 0 (Baseline), Week 1, Week 2, Week 4, Week 8, Week 14, Week 20, Week 26, Week 34, Week 42, Week 52 (Endpoint) ]

10.  Primary:   Mean Change From Baseline in Patient Weight   [ Time Frame: At screening (up to 42 days prior to treatment start), Week 0 (Baseline), Week 1, Week 2, Week 4, Week 8, Week 14, Week 20, Week 26, Week 34, Week 42, Week 52 (Endpoint) ]

11.  Primary:   Mean Change From Baseline by Time Period in Body Weight Z-Score   [ Time Frame: At screening (up to 42 days prior to treatment start), Week 0 (Baseline), Week 1, Week 2, Week 4, Week 8, Week 14, Week 20, Week 26, Week 34, Week 42, Week 52 (Endpoint) ]

12.  Primary:   Mean Change From Baseline in Patient Body Mass Index (BMI)   [ Time Frame: At screening (up to 42 days prior to treatment start), Week 0 (Baseline), Week 1, Week 2, Week 4, Week 8, Week 14, Week 20, Week 26, Week 34, Week 42, Week 52 (Endpoint) ]

13.  Primary:   Mean Change From Baseline By Time Period in BMI Z-Score   [ Time Frame: At screening (up to 42 days prior to treatment start), Week 0 (Baseline), Week 1, Week 2, Week 4, Week 8, Week 14, Week 20, Week 26, Week 34, Week 42, Week 52 (Endpoint) ]

14.  Secondary:   Mean Change From Baseline in Clinical Global Impression (CGI)-Severity Score at Week 52 (Endpoint, LOCF)   [ Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF) ]

15.  Secondary:   CGI-Improvement Score at Week 52 (Endpoint, LOCF)   [ Time Frame: Week 52 (Endpoint, LOCF) ]

16.  Secondary:   Mean Change From Baseline in Aberrant Behavior Checklist (ABC) Irritability Score at Week 52 (Endpoint, LOCF)   [ Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF) ]

17.  Secondary:   Mean Change From Baseline in ABC Hyperactivity Subscale Score at Week 52 (Endpoint, LOCF)   [ Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF) ]

18.  Secondary:   Change From Baseline in ABC Stereotypy Subscale Score at Week 52 (Endpoint, LOCF)   [ Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF) ]

19.  Secondary:   Mean Change From Baseline in ABC Social Withdrawal Scale At Week 52 (Endpoint, LOCF)   [ Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF) ]

20.  Secondary:   Mean Change From Baseline in ABC Inappropriate Speech Subscale Score at Week 52 (Endpoint, LOCF)   [ Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF) ]

21.  Secondary:   Change From Baseline in Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Score at Week 52 (Endpoint, LOCF)   [ Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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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  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.


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


No publications provided by Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications automatically indexed to this study:

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00365859     History of Changes
Other Study ID Numbers: CN138-180
Study First Received: August 15, 2006
Results First Received: December 17, 2009
Last Updated: November 7, 2013
Health Authority: United States: Food and Drug Administration