Clinical trial NCT01227668: Phase IV Long-term Maintenance Study of Aripiprazole in the Treatment of Irritability Associated With Autistic Disorder
Official title: Safety and Efficacy of Aripiprazole in the Long-term Maintenance Treatment of Pediatric Patients With Irritability Associated With Autistic Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Irritability Associated With Autistic Disorder
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-10-25
Enrollment: 215
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether pediatric participants with irritability associated with autistic disorder who have responded to aripiprazole treatment will experience a relapse significantly later when continuing therapy with aripiprazole than will participants who receive placebo

Detailed description: Phase 1: Single blind/ Phase 2: Double blind

Eligibility criteria: Key Inclusion Criteria:

* Male or female children or adolescents, 6 to 17 years of age, inclusive, at the time of the baseline visit
* Meets current diagnostic criteria of the Diagnostic and Statistical Manual-of Mental Disorders IV-Text Revised for autistic disorder and displays behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these problems. Diagnosis of autistic disorder will be confirmed by the Autism Diagnostic Interview-Revised.
* Participant or designated guardian or caregiver is able to comprehend and satisfactorily comply with the protocol requirements, in the opinion of the investigator.
* Demonstrates behaviors such as tantrums, aggression, or self-injury or a combination of these problems
* An Aberrant Behavior Checklist Irritability subscale score ≥18 AND a Clinical Global Impressions Severity score ≥4 at the Screening and Baseline Visits.
* Mental age of at least 24 months

Key Exclusion Criteria:

* Treatment resistant to neuroleptic medication, based on lack of therapeutic response to 2 different neuroleptics after treatment for at least 3 weeks each.
* Previous treatment with aripiprazole for at least 3 weeks duration at an adequate daily dose, without demonstrating a clinically meaningful response.
* Lifetime diagnosis of bipolar disorder, psychosis, or schizophrenia, or a current diagnosis of major depressive disorder
* Diagnosis of Pervasive Developmental Disorder-Not Otherwise Specified, Asperger's Syndrome, Rett's Syndrome, childhood disintegrative disorder, or Fragile X Syndrome
* History of neuroleptic malignant syndrome
* At significant risk for suicide based on history or routine psychiatric status examination
* A seizure within the past year
* History of severe head trauma or stroke
* History or current evidence of any unstable medical conditions that would expose the patient to undue risk of a significant adverse event or interfere with assessments of safety or efficacy during the course of the trial
* Weight lower than 15 kg
* Known allergy or hypersensitivity to aripiprazole or other dihidrocarbostyrils
* History of a clinically significant low white blood cell count or a drug-induced leukopenia/neutropenia
* Any other medically significant abnormal laboratory test or vital sign result or electrocardiogram finding

Primary outcomes:
measure: Percentage of Patients Relapsing by Week 16
timeFrame: From end of Phase 1 (Date of randomization) to Week 16 of Phase 2 and end of treatment
Secondary outcomes:
measure: Adjusted Mean Change From Baseline to Week 16 on the Aberrant Behavior Checklist Irritability (ABC-I) Subscale Score (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline (end of Phase 1) to Week 16 of Phase 2
measure: Change From Baseline in Mean Clinical Global Impression Improvement (CGI-I) Scale Score at Week 16 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline (end of Phase 1) to Week 16 of Phase 2
measure: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation During Phase 1
timeFrame: Weekly from Week 1 to Week 26 and continuously to end of treatment
Other outcomes:
measure: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs During Phase 2
timeFrame: Weekly from Weeks 1 through 16 (end of treatment) of Phase 2
Locations:
city: Dothan
country: United States
facility: Harmonex Neuroscience Research, Inc
state: Alabama
city: Phoenix
country: United States
facility: Southwest Autism Research And Resource Center
state: Arizona
city: Costa Mesa
country: United States
facility: Clinical Innovations, Inc.
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists, Llc
state: California
city: Palo Alto
country: United States
facility: Abbey Neuropsychology Clinic
state: California
city: San Francisco
country: United States
facility: Ucsf - Lppi
state: California
city: Stanford
country: United States
facility: Stanford University School Of Medicine
state: California
city: Washington
country: United States
facility: Children'S National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Hialeah
country: United States
facility: Palm Springs Research Institute
state: Florida
city: Maitland
country: United States
facility: Florida Clinical Research Center, Llc
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: Smyrna
country: United States
facility: Institute For Behavioral Medicine, Llc
state: Georgia
city: Coeur D'Alene
country: United States
facility: Kootenai Behavioral Health Center
state: Idaho
city: Louisville
country: United States
facility: Kosair Charities Pediatric Clinical Research Unit
state: Kentucky
city: Shreveport
country: United States
facility: Lsu Health Sciences Center
state: Louisiana
city: Newton
country: United States
facility: Neurocare, Inc.
state: Massachusetts
city: Bloomfield Hills
country: United States
facility: Neurobehavioral Medicine Group
state: Michigan
city: Las Vegas
country: United States
facility: Center For Psychiatry And Behavioral Medicine, Inc
state: Nevada
city: Gibbsboro
country: United States
facility: Clinical Research Center Of New Jersey
state: New Jersey
city: Toms River
country: United States
facility: Children'S Specialized Hosp
state: New Jersey
city: Stony Brook
country: United States
facility: Stony Brook University School Of Medicine
state: New York
city: Chapel Hill
country: United States
facility: Unc Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Nisonger Center
state: Ohio
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Oklahoma City
country: United States
facility: Ou Physician'S Child Study Center
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Clinical Research, Llc
state: Oklahoma
city: Gresham
country: United States
facility: Cyn3rgy Research
state: Oregon
city: Philadelphia
country: United States
facility: Drexel University College Of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Psychiatric Institute And Clinic
state: Pennsylvania
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Desoto
country: United States
facility: Insite Clinical Research
state: Texas
city: Clinton
country: United States
facility: Ericksen Research And Development
state: Utah
city: Norfolk
country: United States
facility: Childrens Specialty Gr., Pllc
state: Virginia
city: Richmond
country: United States
facility: Virginia Treatment Center For Children
state: Virginia
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Findling RL, Mankoski R, Timko K, Lears K, McCartney T, McQuade RD, Eudicone JM, Amatniek J, Marcus RN, Sheehan JJ. A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder. J Clin Psychiatry. 2014 Jan;75(1):22-30. doi: 10.4088/jcp.13m08500.