Study to Evaluate the Efficacy and Safety of Aripiprazole

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

• 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.

Study Overview

• Status: Unknown
• Conditions: Autism
• Intervention / Treatment: Drug: Aripiprazole

Detailed Description

1. Study design

- Multi-national, Multi-center, 52 weeks open label, single arm design

• Study Type: Interventional
• Enrollment (Anticipated): 79
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Recruiting
    • Samsung Medical Center
    • Principal Investigator: Yoo-Sook Joung, MD., PhD.
  • Seoul, Korea, Republic of, 138-736
    • Not yet recruiting
    • Asan Medical Center
    • Principal Investigator: Hyo-Won Kim, MD,PhD
  • Gyeonggi-do
    • Ilsan, Gyeonggi-do, Korea, Republic of, 411-706
      • Recruiting
      • Inje University Ilsan Paik Hospital
      • Principal Investigator: Eun-Jin Park, MD, PhD.
• Philippines
  • Pasig, Philippines
    • Not yet recruiting
    • Medical City
    • Principal Investigator: Stella Manalo, MD
  • Quezon City, Philippines
    • Not yet recruiting
    • Philippine Children's Medical Center
    • Principal Investigator: Alexis Reyes, MD
• Thailand
  • Bangkok, Thailand, 10700
    • Not yet recruiting
    • Siriraj Hospital Mahidol University
    • Principal Investigator: Vitharon Boon-yasidhi, MD

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aripiprazole; 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; Other Names: Abilify®

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	Safety will be evaluated based on below inormaiton.; Laboratory test results (routine lab. and serum prolactin); Vital signs (blood pressure, pulse, body temperature); ECG; Weight gain; Extrapyramidal side effects (EPSEs) assessed by Simpson-Angus Rating Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS)	Week 1, 2, 4, 8, 12, 24, 36, 52

Collaborators and Investigators

• Sponsor: Yoo-Sook Joung
• Collaborators: Korea Otsuka International Asia Arab
• Investigators: Principal Investigator: Yoo-Sook Joung, MD. PhD., Sumsung Medical Center

Publications and helpful links

General Publications

• Kim BU, Kim HW, Park EJ, Kim JH, Boon-Yasidhi V, Tarugsa J, Reyes A, Manalo SG, Joung YS. Long-Term Improvement and Safety of Aripiprazole for Irritability and Adaptive Function in Asian Children and Adolescents with Autistic Disorder: A 52-Week, Multinational, Multicenter, Open-Label Study. J Child Adolesc Psychopharmacol. 2022 Sep;32(7):390-399. doi: 10.1089/cap.2022.0004.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): February 1, 2016

Study Registration Dates

• First Submitted: February 13, 2014
• First Submitted That Met QC Criteria: February 20, 2014
• First Posted (Estimate): February 24, 2014

Study Record Updates

• Last Update Posted (Estimate): March 11, 2014
• Last Update Submitted That Met QC Criteria: March 10, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Aripiprazole; Autism; Abilify
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: 031OTC1301