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

A Multicenter Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study With Three Fixed Doses of Aripiprazole in the Treatment of Children and Adolescents With Autistic Disorder (AD)

This study will compare the effectiveness (how well the drug works) of aripiprazole with placebo (fixed dose) in reducing serious behavioral problems in children and adolescents with a diagnosis of autistic disorder (AD).

Study Overview

• Status: Completed
• Conditions: Behavioral Symptoms; Autistic Disorder
• Intervention / Treatment: Drug: Aripiprazole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Dothan, Alabama, United States, 36303
      • Harmonex Neuroscience
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Southwest Autism Research and Resource Center
  • California
    • Huntington Beach, California, United States, 92647
      • Clinical Innovations, Inc.
    • Sacramento, California, United States, 95817
      • University Of California-Davis Medical Center
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • The Children's Hospital
  • Florida
    • Boca Raton, Florida, United States, 33432
      • Marsella, Gregory
    • Gainesville, Florida, United States, 32611
      • University of Florida
    • Tampa, Florida, United States, 33613
      • University of South Florida
  • Georgia
    • Smyrna, Georgia, United States, 30080
      • Institute For Behavioral Medicine
  • Illinois
    • Chicago, Illinois, United States, 60606
      • University of Illinois at Chicago
  • Massachusetts
    • Medford, Massachusetts, United States, 02139
      • Cambridge Health Alliance
    • Wellesley, Massachusetts, United States, 02481
      • Ladders Clinic
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Munroe-Meyer Institute
  • New York
    • Bethpage, New York, United States, 11714
      • North Shore - Long Island Jewish Health System
    • New York, New York, United States, 10029
      • Seaver And New York Autism Center Of Excellence
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals
    • Durham, North Carolina, United States, 27710
      • Duke Child And Family Study Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Nisonger Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Cutting Edge Research
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15203
      • Western Psychiatric Institute And Clinic
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Pediatric Neurology Associates
    • Houston, Texas, United States, 77007
      • Bayou City Research, Ltd.
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Children's National Medical Center
  • Washington
    • Bothell, Washington, United States, 98011
      • Pacific Institute Of Medical Sciences
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53201
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meets current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for AD and demonstrates serious behavioral problems; diagnosis confirmed by Autism, Diagnostic Interview-Revised (ADI-R).
• CGI score > = 4 AND an ABC Irritability/Agitation subscale score > = 18 at screening and baseline (randomization)
• Mental age of at least 18 months
• Male or female 6 to 17 years of age inclusive, at the time of randomization

Exclusion Criteria:

• Patients considered treatment resistant to neuroleptic medication based on lack of therapeutic response to 2 different neuroleptics after treatment of at least 3 weeks each
• Patients previously treated and not responding to aripiprazole treatment
• The patient is currently diagnosed with another disorder on the autism spectrum, including PDD-NOS, Asperger's Disorder, Rett's Disorder, Fragile-X Syndrome or Childhood Disintegrative Disorder
• Current diagnosis of bipolar disorder, psychosis, schizophrenia, or major depression
• A seizure in the past year
• History of severe head trauma or stroke
• Non-pharmacologic therapy (e.g., psychotherapy, behavior modification) should be stable prior to screening and consistent throughout the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A1; 5 mg	Drug: Aripiprazole; Tablets, Oral, once daily, 8 weeks; Other Names: Abilify
Experimental: A2; 10 mg	Drug: Aripiprazole; Tablets, Oral, once daily, 8 weeks; Other Names: Abilify
Experimental: A3; 15 mg	Drug: Aripiprazole; Tablets, Oral, once daily, 8 weeks; Other Names: Abilify
Placebo Comparator: B1	Drug: Placebo; Tablets, Oral, once daily, 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change (Week 8 - Baseline) in the Autistic Behavior Checklist (ABC) Irritability Subscale Score	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.	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Clinical Global Impressions Improvement Scale (CGI-I) Score	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).	Week 8
Number of Participants With Response at Week 8	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.	Week 8
Mean Change (Week 8 - Baseline) in the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS; Compulsion Scale Only)	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.	Week 8
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores	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.	Week 8
Mean Change (Week 8 - Baseline) in CGI-Severity (CGI-S)	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.	Week 8
Summary of Safety	Deaths, Adverse Events (AEs), Serious AEs (SAEs), Treatment-Emergent AEs and AEs leading to discontinuation	continuously throughout the study
Change From Baseline in Body Weight	Adjusted mean change (Week 8 - baseline) in body weight	Week 8

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: Otsuka America Pharmaceutical
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Marcus RN, Owen R, Kamen L, Manos G, McQuade RD, Carson WH, Aman MG. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry. 2009 Nov;48(11):1110-1119. doi: 10.1097/CHI.0b013e3181b76658.
• Mankoski R, Stockton G, Manos G, Marler S, McQuade R, Forbes RA, Marcus R. Aripiprazole treatment of irritability associated with autistic disorder and the relationship between prior antipsychotic exposure, adverse events, and weight change. J Child Adolesc Psychopharmacol. 2013 Oct;23(8):572-6. doi: 10.1089/cap.2012.0075.
• Robb AS, Andersson C, Bellocchio EE, Manos G, Rojas-Fernandez C, Mathew S, Marcus R, Owen R, Mankoski R. Safety and tolerability of aripiprazole in the treatment of irritability associated with autistic disorder in pediatric subjects (6-17 years old):results from a pooled analysis of 2 studies. Prim Care Companion CNS Disord. 2011;13(1):PCC.10m01008. doi: 10.4088/PCC.10m01008gry.

Helpful Links

• Otsuka Clinical Trial Website
• Otsuka Clinical Trial Transparency

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2006
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: June 13, 2006
• First Submitted That Met QC Criteria: June 15, 2006
• First Posted (Estimated): June 16, 2006

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Serious behavioral problems in children and adolescents with AD
• Additional Relevant MeSH Terms: Autism Spectrum Disorder; Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Behavior; Autistic Disorder; Behavioral Symptoms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinolones; Quinolines; Piperazines; Aripiprazole
• Other Study ID Numbers: CN138-179

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No