Clinical trial NCT00365859: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Autistic Disorder
Behavioral Symptoms
Keywords: Serious behavioral problems in children and adolescents with AD
behavioral problems
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Otsuka America Pharmaceutical
First posted: 2006-08-18
Enrollment: 330
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 \[NCT00337571\]).


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (AEs), Deaths, AEs Leading to Discontinuation, Extra Pyramidal Syndrome (EPS)-Related AEs
timeFrame: 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
measure: Mean Change From Baseline in Total Simpson-Angus Scale (SAS) At Week 8, Week 26, and Week 52
timeFrame: Baseline, Week 8, Week 26, Week 52
measure: Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) At Week 8, Week 26, and Week 52
timeFrame: Baseline, Week 8, Week 26, Week 52
measure: Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Week 8, Week 26, Week 52, and Endpoint
timeFrame: Baseline, Week 8, Week 26, Week 52
measure: Number of Participants With Potentially Clinically Relevant Laboratory Metabolic Abnormalities
timeFrame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
measure: Number of Participants With Potentially Clinically Relevant Laboratory Hematology Abnormalities
timeFrame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
measure: Number of Participants With Potentially Clinically Relevant Laboratory Chemistry Abnormalities
timeFrame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
measure: Number of Participants With Potentially Clinically Relevant Eletrocardiograph (ECG) Abnormalities
timeFrame: At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
measure: Number of Potentially Clinically Relevant Vital Sign Abnormalities
timeFrame: 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)
measure: Mean Change From Baseline in Patient Weight
timeFrame: 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)
measure: Mean Change From Baseline by Time Period in Body Weight Z-Score
timeFrame: 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)
measure: Mean Change From Baseline in Patient Body Mass Index (BMI)
timeFrame: 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)
measure: Mean Change From Baseline By Time Period in BMI Z-Score
timeFrame: 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)
Secondary outcomes:
measure: Mean Change From Baseline in Clinical Global Impression (CGI)-Severity Score at Week 52 (Endpoint, LOCF)
timeFrame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
measure: CGI-Improvement Score at Week 52 (Endpoint, LOCF)
timeFrame: Week 52 (Endpoint, LOCF)
measure: Mean Change From Baseline in Aberrant Behavior Checklist (ABC) Irritability Score at Week 52 (Endpoint, LOCF)
timeFrame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
measure: Mean Change From Baseline in ABC Hyperactivity Subscale Score at Week 52 (Endpoint, LOCF)
timeFrame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
measure: Change From Baseline in ABC Stereotypy Subscale Score at Week 52 (Endpoint, LOCF)
timeFrame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
measure: Mean Change From Baseline in ABC Social Withdrawal Scale At Week 52 (Endpoint, LOCF)
timeFrame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
measure: Mean Change From Baseline in ABC Inappropriate Speech Subscale Score at Week 52 (Endpoint, LOCF)
timeFrame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
measure: Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Score at Week 52 (Endpoint, LOCF)
timeFrame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Dothan
country: United States
facility: Harmonex Neuroscience
state: Alabama
city: Phoenix
country: United States
facility: Southwest Autism Research and Resource Center
state: Arizona
city: Tuscon
country: United States
facility: Univ of Arizona
state: Arizona
city: Costa Mesa
country: United States
facility: Clinical Innovations, Inc
state: California
city: Rolling Hills Estate
country: United States
facility: Peninsula Research Assoc
state: California
city: Sacramento
country: United States
facility: University Of California-Davis Health Science Center
state: California
city: San Diego
country: United States
facility: Sharp Mesa Vista Hospital
state: California
city: Stanford
country: United States
facility: Stanford University School Of Medicine
state: California
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Boca Raton
country: United States
facility: Offices of Gregory Marsella, MD, PA
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Winter Park
country: United States
facility: Children's Developmental Center
state: Florida
city: Atlanta
country: United States
facility: Child Neurology Associates, PC
state: Georgia
city: Smyrna
country: United States
facility: Institute For Behavioral Medicine
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Cambridge
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Cambridge
country: United States
facility: Cambridge Health Alliance
state: Massachusetts
city: Wellsley
country: United States
facility: Ladders Clinic
state: Massachusetts
city: Bloomfield Hills
country: United States
facility: Neurobehavioral Medicine Group
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital Of Michigan
state: Michigan
city: St. Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital and Clinics
state: Missouri
city: Omaha
country: United States
facility: Munroe-Meyer Institute Diagnostic Center
state: Nebraska
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine
state: Nevada
city: Toms River
country: United States
facility: Children's Specialized Hospital
state: New Jersey
city: Bethpage
country: United States
facility: North Shore - Long Island Jewish Health System
state: New York
city: New York
country: United States
facility: Seaver and New York Autism Center of Excellence
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Stony Brook
country: United States
facility: SUNY at Stony Brook - School of Medicine
state: New York
city: Asheville
country: United States
facility: Mission Hospitals - Mission Children's Clinics
state: North Carolina
city: Chapel Hill
country: United States
facility: University of NC
state: North Carolina
city: Durham
country: United States
facility: Duke Child and Family Study Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Columbus
country: United States
facility: The Nisonger Center
state: Ohio
city: Oklahoma City
country: United States
facility: Cutting Edge Research
state: Oklahoma
city: Pittsburgh
country: United States
facility: Western Psychiatric Institute and Clinic
state: Pennsylvania
city: Memphis
country: United States
facility: UT Medical Group, Department Of Psychiatry
state: Tennessee
city: Dallas
country: United States
facility: Dallas Pediatric Neurology Associates
state: Texas
city: Houston
country: United States
facility: Bayou City Research, Ltd.
state: Texas
city: Houston
country: United States
facility: Red Oak Psychiatry Associates, PA
state: Texas
city: San Antonio
country: United States
facility: North San Antonio Healthcare Associates
state: Texas
city: Fairfax
country: United States
facility: Children's National Medical Center
state: Virginia
city: Herndon
country: United States
facility: Neuroscience, Inc
state: Virginia
city: Norfolk
country: United States
facility: Monarch Research Associates
state: Virginia
city: Richmond
country: United States
facility: Virginia Treatment Center For Children
state: Virginia
city: Bothell
country: United States
facility: Pacific Institute of Medical Sciences
state: Washington
city: Seattle
country: United States
facility: Autism Spectrum Treatment and Research Center
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Marcus RN, Owen R, Manos G, Mankoski R, Kamen L, McQuade RD, Carson WH, Findling RL. Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder: a 52-week, open-label, multicenter study. J Clin Psychiatry. 2011 Sep;72(9):1270-6. doi: 10.4088/JCP.09m05933. Epub 2011 Jul 26.
citation: Marcus RN, Owen R, Manos G, Mankoski R, Kamen L, McQuade RD, Carson WH, Corey-Lisle PK, Aman MG. Aripiprazole in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder: results from a 52-week, open-label study. J Child Adolesc Psychopharmacol. 2011 Jun;21(3):229-36. doi: 10.1089/cap.2009.0121.