Study to Evaluate the Efficacy and Safety of Aripiprazole

Study Overview
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Brief Summary
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To evaluate the efficacy of flexibly dosed aripiprazole in reducing serious behavioral problems in Asian children and adolescents with a diagnosis of autism spectrum disorder, as measured by change from baseline to endpoint on the irritability subscale of the aberrant behavior checklist (ABC-I). To evaluate the long-term safety and tolerability of flexibly dosed aripiprazole in the treatment of serious behavioral problems in Asian children and adolescents with a diagnosis of autism spectrum disorder.

Detailed Description
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1. Study design - Multi-national, Multi-center, 52 weeks open label, single arm design

Official Title
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A Multinational, Multicenter, Open-label, Single-arm Study to Evaluate the Efficacy and Safety of Aripiprazole in Asian Pediatric Patients With Autism Spectrum Disorder and Behavior Problems

Conditions
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Autism

Intervention / Treatment
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* Drug: Aripiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 6 to 17 years of age. Meeting the diagnostic criteria for autistic disorder specified by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), with a diagnosis corroborated by the Autism Diagnostic Interview-Revised (ADI-R) diagnostic instrument and demonstrated behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these. Clinical Global Impressions (CGI) Severity subscale score ≥ 4 at screening and baseline. Aberrant Behavior Checklist (ABC) Irritability subscale score ≥18 at screening and baseline. Mental age ≥ 18 months. Women of childbearing potential (WOCBP) have to use an adequate method of contraception WOCBP must have had a negative serum or urine pregnancy test. The patient and/or the designated guardian(s) or caregiver(s) who are able to comprehend and comply with the protocol requirements, in the opinion of the investigator and have consented to participate by signing an informed consent form. Exclusion Criteria: Current diagnosis of bipolar disorder, schizophrenia, major depressive disorder, Rett's disorder, or Fragile-X syndrome. History of neuroleptic malignant syndrome. Significant risk of committing suicide based on history or routine psychiatric status examination. History of seizure in the past 1 year. History of severe head trauma or stroke History or current evidence of any unstable medical conditions Patient considered treatment resistant to neuroleptic medication Patient considered treatment resistant to aripiprazole Woman who is pregnant or breastfeeding ECG: QTc > 475 msec Platelets ≤ 75,000/μL Hemoglobin ≤ 9 g/dL Neutrophils ≤ 1.0x10^3/μL Aspartate or alanine transaminase (AST or ALT) > 3xULN Serum creatinine ≥ 2 mg/dL Patient weighed < 15 kg Patient who participated in any other clinical trial within 4 weeks Patient determined to require the administration of the prohibited medications during the study period Patient with other conditions determined by the investigator to be inappropriate for this clinical 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aripiprazole<br>Dose level: 2, 5, 10, 15 mg/day Starting dose: 2 mg/day Dose increment: The dose should be gradually increased according to the investigator's judgment of subject's response. Target dose: 5-15 mg/day Maximum dose: 15 mg/day Flexibly dosed (2 to 15 mg/day) aripiprazole (oral tablet or solution) is taken once in a day at the same time without regarding to meals | Drug: Aripiprazole<br> <br> * Other names: Abilify®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| irritability subscale of the aberrant behavior checklist | Mean change from baseline to endpoint of Part 1 (week 12)in the caregiver-rated ABC Irritability (ABC-I) subscale score. ABC Scale will be completed by subject | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in ABC-subscale of lethargy/social withdrawal, stereotypic behavior, hyperactivity, inappropriate speech | ABC Scale will be completed by subject | Week 1, 2, 4, 8, 12, 24, 36, 52 | 
| Change of CGI-S, CGI-I from baseline | CGI-S, CGI-I scale will be evaluated by investigator | Week 1, 2, 4, 8, 12, 24, 36, 52 | 
| Change of Behavioral problems from baseline | Behavioral problems scale: Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) | Week 12, 52 | 
| Change of Adaptive Skills from baseline | Adaptive Skills Scale: Vineland Adaptive Behavior Scale (VABS) | week 12, 52 | 
| Change of Parental stress from baseline | Parental stress scale: Parenting Stress Index (PSI) | Weekk 12, 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Abilify, Autism, Aripiprazole