Phase IV Long-term Maintenance Study of Aripiprazole in the Treatment of Irritability Associated With Autistic Disorder

NCT01227668 | Completed Phase 4 Results

• 1 other identifier: CN138-603
• Study Type: interventional
• Target: 215
• Locations: 1 country
• Sites: 38

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

Conditions

Irritability Associated With Autistic Disorder

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Relapsing by Week 16

  Time of relapse=date when patient meets relapse criteria. There are 4 definitions for relapse: 1. Patient meets the following criteria for 2 consecutive visits: (a) Aberrant Behavior Checklist Irritability score ≥25% than score at end of Phase 1 AND (b) Clinical Global Impression Improvement scale rating of 'Much Worse' or 'Very Much Worse' relative to rating at end of Phase 1. If relapse criteria met at 1 visit, 2nd visit should occur in about 1 week to reevaluate whether relapse criteria are still met. 2. Patient discontinues for "Lost to Follow-up" after a visit in which he or she met Definition 1 criteria (a\&b). 3. Patient begins a prohibited drug (whether a study investigator or outside source prescribed) to treat worsening symptoms of irritability of autistic disorder after a visit where patient met Definition 1 criteria (a\&b). 4. Patient discontinues due to hospitalization for worsening symptoms of irritability or due to lack of efficacy based on investigator's assessment.

  From end of Phase 1 (Date of randomization) to Week 16 of Phase 2 and end of treatment

Secondary Outcomes (3)

• Adjusted Mean Change From Baseline to Week 16 on the Aberrant Behavior Checklist Irritability (ABC-I) Subscale Score (Last Observation Carried Forward [LOCF])

  From Baseline (end of Phase 1) to Week 16 of Phase 2

• Change From Baseline in Mean Clinical Global Impression Improvement (CGI-I) Scale Score at Week 16 (Last Observation Carried Forward [LOCF])

  From Baseline (end of Phase 1) to Week 16 of Phase 2

• Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation During Phase 1

  Weekly from Week 1 to Week 26 and continuously to end of treatment

Other Outcomes (1)

• Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs During Phase 2

  Weekly from Weeks 1 through 16 (end of treatment) of Phase 2

Study Arms (2)

Aripiprazole

EXPERIMENTAL

Drug: Aripiprazole

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Aripiprazole DRUG

Tablets, Oral, 2-15 mg, once daily, 13-42 weeks

Also known as: BMS-337039, Abilify

Aripiprazole

Placebo DRUG

Tablets, Oral, 0 mg, once daily, 16 weeks

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (38)

Harmonex Neuroscience Research, Inc

Dothan, Alabama, 36303, United States

Location

Southwest Autism Research And Resource Center

Phoenix, Arizona, 85006, United States

Location

Clinical Innovations, Inc.

Costa Mesa, California, 92626, United States

Location

Behavioral Research Specialists, Llc

Glendale, California, 91206, United States

Location

Abbey Neuropsychology Clinic

Palo Alto, California, 94306, United States

Location

Ucsf - Lppi

San Francisco, California, 94143, United States

Location

Stanford University School Of Medicine

Stanford, California, 94305, United States

Location

Children'S National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

Palm Springs Research Institute

Hialeah, Florida, 33012, United States

Location

Florida Clinical Research Center, Llc

Maitland, Florida, 32751, United States

Location

Miami Children'S Hospital

Miami, Florida, 33155, United States

Location

University Of South Florida

Tampa, Florida, 33613, United States

Location

Institute For Behavioral Medicine, Llc

Smyrna, Georgia, 30080, United States

Location

Kootenai Behavioral Health Center

Coeur d'Alene, Idaho, 83814, United States

Location

Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, 40202, United States

Location

Lsu Health Sciences Center

Shreveport, Louisiana, 71103, United States

Location

Neurocare, Inc.

Newton, Massachusetts, 02459, United States

Location

Neurobehavioral Medicine Group

Bloomfield Hills, Michigan, 48302, United States

Location

Center For Psychiatry And Behavioral Medicine, Inc

Las Vegas, Nevada, 89128, United States

Location

Clinical Research Center Of New Jersey

Gibbsboro, New Jersey, 08026, United States

Location

Children'S Specialized Hosp

Toms River, New Jersey, 08755, United States

Location

Stony Brook University School Of Medicine

Stony Brook, New York, 11794, United States

Location

Unc Chapel Hill

Chapel Hill, North Carolina, 27517, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44104, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

The Ohio State University Nisonger Center

Columbus, Ohio, 43210, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, 73116, United States

Location

Ou Physician'S Child Study Center

Oklahoma City, Oklahoma, 73117, United States

Location

Tulsa Clinical Research, Llc

Tulsa, Oklahoma, 74104, United States

Location

Cyn3rgy Research

Gresham, Oregon, 97030, United States

Location

Drexel University College Of Medicine

Philadelphia, Pennsylvania, 19124, United States

Location

Western Psychiatric Institute And Clinic

Pittsburgh, Pennsylvania, 15203, United States

Location

Holston Medical Group

Kingsport, Tennessee, 37660, United States

Location

Insite Clinical Research

DeSoto, Texas, 75115, United States

Location

Ericksen Research And Development

Clinton, Utah, 84015, United States

Location

Childrens Specialty Gr., Pllc

Norfolk, Virginia, 23510, United States

Location

Virginia Treatment Center For Children

Richmond, Virginia, 23298, United States

Location

Related Publications (2)

• Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

  PMID: 37811711 DERIVED

• 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.

  PMID: 24502859 DERIVED

Related Links

• Investigator Inquiry form

MeSH Terms

Interventions

Aripiprazole

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2010
• First Posted: October 25, 2010
• Study Start: March 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: May 2, 2014
• Results First Posted: May 2, 2014

Record last verified: 2014-03

Locations

US (38)