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

Official Title: “A 52-Week, Open-Label, Multicenter Study of the Safety and Tolerability of Aripiprazole Flexibly Dosed in the Treatment of Children and Adolescents With Autistic Disorder”

This study will provide long-term safety data for patients who are taking aripiprazole for up to 1 year. Most patients enrolled in this study will have participated in a short-term study with aripiprazole (CN138-178 [NCT00332241] or CN138-179 [NCT00337571]).

Intervention(s) in this Clinical Trial

• Drug: Aripiprazole
  • Tablets, Oral, 2, 5, 10, or 15 mg, once daily, 52 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: De Novo
  • De novo participants (those who did not participate in protocol (CN138-178 [NCT00332241] or CN138-179 [NCT00337571]) assigned to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.
• Experimental: Rollover Placebo
  • Participants who completed participation in protocol (CN138-178 [NCT00332241] or CN138-179 [NCT00337571]) on placebo treatment and continued to meet all of the inclusion criteria and none of the exclusion criteria. Assigned in this study to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.
• Experimental: Rollover Aripiprazole
  • Participants who completed participation in protocol CN138-178 [NCT00332241] or CN138-179 [NCT00337571] on aripiprazole treatment and continued to meet all of the inclusion criteria and none of the exclusion criteria. Assigned in this study to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.

Primary Measures

• Number of Participants With Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (AEs), Deaths, AEs Leading to Discontinuation, Extra Pyramidal Syndrome (EPS)-Related AEs
  • Time Frame: From Screening (up to 42 days prior to treatment start) through Week 52 (end of study) for SAEs; from Week 0 (Baseline) through Week 52 (End of Study) for AEs
    Safety Issue?: Yes
• Mean Change From Baseline in Total Simpson-Angus Scale (SAS) At Week 8, Week 26, and Week 52
  • Time Frame: Baseline, Week 8, Week 26, Week 52
    Safety Issue?: Yes
• Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) At Week 8, Week 26, and Week 52
  • Time Frame: Baseline, Week 8, Week 26, Week 52
    Safety Issue?: Yes
• Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Week 8, Week 26, Week 52, and Endpoint
  • Time Frame: Baseline, Week 8, Week 26, Week 52
    Safety Issue?: Yes
• Number of Participants With Potentially Clinically Relevant Laboratory Metabolic Abnormalities
  • Time Frame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
    Safety Issue?: Yes
• Number of Participants With Potentially Clinically Relevant Laboratory Hematology Abnormalities
  • Time Frame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
    Safety Issue?: Yes
• Number of Participants With Potentially Clinically Relevant Laboratory Chemistry Abnormalities
  • Time Frame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
    Safety Issue?: Yes
• Number of Participants With Potentially Clinically Relevant Eletrocardiograph (ECG) Abnormalities
  • Time Frame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
    Safety Issue?: Yes
• Number of Potentially Clinically Relevant Vital Sign Abnormalities
  • Time Frame: At screening (up to 42 days prior to treatment start), Week 0 (Baseline), Week 1, Week 2, Week 4, Week 8, Week 14, Week 20, Week 26, Week 34, Week 42, Week 52 (Endpoint)
    Safety Issue?: Yes
• Mean Change From Baseline in Patient Weight
  • Time Frame: At screening (up to 42 days prior to treatment start), Week 0 (Baseline), Week 1, Week 2, Week 4, Week 8, Week 14, Week 20, Week 26, Week 34, Week 42, Week 52 (Endpoint)
    Safety Issue?: Yes
• Mean Change From Baseline by Time Period in Body Weight Z-Score
  • Time Frame: At screening (up to 42 days prior to treatment start), Week 0 (Baseline), Week 1, Week 2, Week 4, Week 8, Week 14, Week 20, Week 26, Week 34, Week 42, Week 52 (Endpoint)
    Safety Issue?: Yes
• Mean Change From Baseline in Patient Body Mass Index (BMI)
  • Time Frame: At screening (up to 42 days prior to treatment start), Week 0 (Baseline), Week 1, Week 2, Week 4, Week 8, Week 14, Week 20, Week 26, Week 34, Week 42, Week 52 (Endpoint)
    Safety Issue?: Yes
• Mean Change From Baseline By Time Period in BMI Z-Score
  • Time Frame: At screening (up to 42 days prior to treatment start), Week 0 (Baseline), Week 1, Week 2, Week 4, Week 8, Week 14, Week 20, Week 26, Week 34, Week 42, Week 52 (Endpoint)
    Safety Issue?: Yes

Secondary Measures

• Mean Change From Baseline in Clinical Global Impression (CGI)-Severity Score at Week 52 (Endpoint, LOCF)
  • Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
    Safety Issue?: No
• CGI-Improvement Score at Week 52 (Endpoint, LOCF)
  • Time Frame: Week 52 (Endpoint, LOCF)
    Safety Issue?: No
• Mean Change From Baseline in Aberrant Behavior Checklist (ABC) Irritability Score at Week 52 (Endpoint, LOCF)
  • Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
    Safety Issue?: No
• Mean Change From Baseline in ABC Hyperactivity Subscale Score at Week 52 (Endpoint, LOCF)
  • Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
    Safety Issue?: No
• Change From Baseline in ABC Stereotypy Subscale Score at Week 52 (Endpoint, LOCF)
  • Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
    Safety Issue?: No
• Mean Change From Baseline in ABC Social Withdrawal Scale At Week 52 (Endpoint, LOCF)
  • Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
    Safety Issue?: No
• Mean Change From Baseline in ABC Inappropriate Speech Subscale Score at Week 52 (Endpoint, LOCF)
  • Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
    Safety Issue?: No
• Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Score at Week 52 (Endpoint, LOCF)
  • Time Frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
    Safety Issue?: No

Inclusion Criteria - Rollover:

• Completed 8 weeks of treatment in one of the following double-blind clinical trials:
• CN138-178 [NCT00332241] or CN138-179 [NCT00337571]
• No significant protocol violations and sufficient medical justification to continue on open-label treatment with aripiprazole

Inclusion Criteria - De Novo:

• 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) or the patient meets the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV TR) diagnostic criteria for AD and has a history of behavioral problems that are currently being treated with psychotropic medication
• Mental age of at least 18 months
• Male or female 6 to 17 years of age, inclusive, at the time of enrollment

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 pervasive developmental disorder-not otherwise specified (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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Years

Maximum Age for this Clinical Trial: 17 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Bristol-Myers Squibb Industry

Overall Clinical Trial Officials and Contacts

Bristol-Myers Squibb Study Director Bristol-Myers Squibb  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00365859

Study ID Number: CN138-180

ClinicalTrials.gov Identifier: NCT00365859

Health Authority: United States: Food and Drug Administration

BMS Clinical Trials Disclosure

Investigator Inquiry form

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm

Centers for Disease Control and Prevention (CDC) algorithm for BMI and body weight z-scores