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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Behavioral Symptoms, Autistic Disorder

Intervention / Treatment
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* Drug: Aripiprazole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1<br>5 mg | Drug: Aripiprazole<br>* Tablets, Oral, once daily, 8 weeks<br>* Other names: Abilify;|
| Experimental: A2<br>10 mg | Drug: Aripiprazole<br>* Tablets, Oral, once daily, 8 weeks<br>* Other names: Abilify;|
| Experimental: A3<br>15 mg | Drug: Aripiprazole<br>* Tablets, Oral, once daily, 8 weeks<br>* Other names: Abilify;|
| Placebo Comparator: B1<br> | Drug: Placebo<br>* Tablets, Oral, once daily, 8 weeks<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Serious behavioral problems in children and adolescents with AD