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

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

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.
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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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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

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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) ]

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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) ]

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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) ]

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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) ]

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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) ]

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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) ]

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15. Secondary:

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

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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) ]

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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) ]

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18. Secondary:

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

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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) ]

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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) ]

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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) ]

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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
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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 by Bristol-Myers Squibb

Publications automatically indexed to this study:

Marcus RN, Owen R, Manos G, Mankoski R, Kamen L, McQuade RD, Carson WH, Findling RL. Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder: a 52-week, open-label, multicenter study. J Clin Psychiatry. 2011 Sep;72(9):1270-6. Epub 2011 Jul 26.

Marcus RN, Owen R, Manos G, Mankoski R, Kamen L, McQuade RD, Carson WH, Corey-Lisle PK, Aman MG. Aripiprazole in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder: results from a 52-week, open-label study. J Child Adolesc Psychopharmacol. 2011 Jun;21(3):229-36.

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:	June 28, 2010
Health Authority:	United States: Food and Drug Administration