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

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

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Boca Raton, Florida, United States, 33432
      • Marsella, Gregory
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Child Neurology Associates, PC
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • NeuroBehavioral Medicine Group
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center for Psychiatry and Behavioral Medicine
  • New York
    • Stony Brook, New York, United States, 11794
      • Suny - Stony Brook School Of Medicine
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Univ Of Nc
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Ut Medical Group
  • Texas
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates, PA

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 for Mental Disorders-Fourth Edition (DSM-IV) diagnostic criteria for AD and demonstrates serious behavioral problems. Diagnosis confirmed by Autism Diagnostic Interview- Revised (ADI-R)
• CGI score > = 4 AND and Aberrant Behavior Checklist (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, or schizophrenia, or major depression
• A seizure in the past year
• History of severe head trauma or stroke
• Patients undergoing non-pharmacologic therapies (e.g., psychotherapy, behavioral modification) must have started at least 2 months prior to the initial screening visit and must remain in a consistent treatment program for the duration of 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

2

Arms and Interventions

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

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
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
Change From Baseline in Body Weight	Adjusted mean change (Week 8 - baseline) in body weight	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 decrease 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
Summary of Safety	Deaths, Adverse Events (AEs), Serious AEs (SAEs), Treatment-Emergent AEs and AEs leading to discontinuation	continuous throughout the study

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: Otsuka America Pharmaceutical

Publications and helpful links

General Publications

• 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.
• Owen R, Sikich L, Marcus RN, Corey-Lisle P, Manos G, McQuade RD, Carson WH, Findling RL. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics. 2009 Dec;124(6):1533-40. doi: 10.1542/peds.2008-3782.
• Aman MG, Kasper W, Manos G, Mathew S, Marcus R, Owen R, Mankoski R. Line-item analysis of the Aberrant Behavior Checklist: results from two studies of aripiprazole in the treatment of irritability associated with autistic disorder. J Child Adolesc Psychopharmacol. 2010 Oct;20(5):415-22. doi: 10.1089/cap.2009.0120.

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): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: May 31, 2006
• First Submitted That Met QC Criteria: May 31, 2006
• First Posted (Estimated): June 1, 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; Behavioral Problems
• Additional Relevant MeSH Terms: Autism Spectrum Disorder; Mental Disorders; Behavioral Symptoms; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Behavior; Child Behavior; Problem Behavior; Autistic Disorder; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinolones; Quinolines; Piperazines; Aripiprazole
• Other Study ID Numbers: CN138-178