Back to resultsPhase IV Long-term Maintenance Study of Aripiprazole in the Treatment of Irritability Associated With Autistic Disorder
Primary Purpose
Irritability Associated With Autistic Disorder
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Aripiprazole
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Irritability Associated With Autistic Disorder
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
Sites / Locations
- Harmonex Neuroscience Research, Inc
- Southwest Autism Research And Resource Center
- Clinical Innovations, Inc.
- Behavioral Research Specialists, Llc
- Abbey Neuropsychology Clinic
- Ucsf - Lppi
- Stanford University School Of Medicine
- Children'S National Medical Center
- Sarkis Clinical Trials
- Palm Springs Research Institute
- Florida Clinical Research Center, Llc
- Miami Children'S Hospital
- University Of South Florida
- Institute For Behavioral Medicine, Llc
- Kootenai Behavioral Health Center
- Kosair Charities Pediatric Clinical Research Unit
- Lsu Health Sciences Center
- Neurocare, Inc.
- Neurobehavioral Medicine Group
- Center For Psychiatry And Behavioral Medicine, Inc
- Clinical Research Center Of New Jersey
- Children'S Specialized Hosp
- Stony Brook University School Of Medicine
- Unc Chapel Hill
- Cleveland Clinic
- University Hospitals Case Medical Center
- The Ohio State University Nisonger Center
- Cutting Edge Research Group
- Ou Physician'S Child Study Center
- Tulsa Clinical Research, Llc
- Cyn3rgy Research
- Drexel University College Of Medicine
- Western Psychiatric Institute And Clinic
- Holston Medical Group
- Insite Clinical Research
- Ericksen Research And Development
- Childrens Specialty Gr., Pllc
- Virginia Treatment Center For Children
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Aripiprazole
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Adjusted Mean Change From Baseline to Week 16 on the Aberrant Behavior Checklist Irritability (ABC-I) Subscale Score (Last Observation Carried Forward [LOCF])
ABC is an informant-based checklist used to assess and classify problem behaviors of children and adolescents with mental retardation. The 58 items are rated on a 4-point scale (0=not at all a problem to 3=the problem is severe in degree), and resolve into 5 subscales: 1) irritability, agitation; 2) lethargy, social withdrawal; 3) stereotypic behavior; 4) hyperactivity, noncompliance; and 5) inappropriate speech. The ABC can be completed by parents, special educators, psychologists, direct caregivers, nurses, and others knowing the participant. Psychometric assessment of the ABC indicates that its subscales have high internal consistency, adequate reliability, and established validity. The ABC-I Subscale Score ranges from 0 to 45, with a negative change in score signifying improvement. LOCF data set includes data recorded at a given visit or, if no observation was recorded at that visit, data carried forward from the prior visit. chg=change; BL=baseline; APR=aripiprazole; vs=versus.
Change From Baseline in Mean Clinical Global Impression Improvement (CGI-I) Scale Score at Week 16 (Last Observation Carried Forward [LOCF])
CG-I rating scale permits global evaluation of patient's improvement over time. At baseline (BL), CGI Severity of Illness assessment is performed, in which the clinician rates severity of patient's condition on a 7-point scale ranging from 1=no symptoms to 7=very severe symptoms. Higher total score=worse symptoms. At subsequent visits, clinician assesses patient's improvement relative to symptoms at baseline on CGI-I 7-point scale ranging from 1=very much improved to 7=very much worse. Since the drug targets irritability symptoms, the CGI focuses on severity of irritability secondary to autistic disorder. Lower score=more improved symptoms. LOCF data set includes data recorded at a given visit or, if nothing recorded, data areccarried forward from the prior visit. For secondary endpoints (endpt), hierarchical testing was used to keep overall experiment-wise type I error rate to <=0.05. diff=difference; IS=irritability scale; PA=primary analysis; signif=significance/significantly.
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation During Phase 1
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01227668
Brief Title
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
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Irritability Associated With Autistic Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
215 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aripiprazole
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Other Intervention Name(s)
BMS-337039, Abilify
Intervention Description
Tablets, Oral, 2-15 mg, once daily, 13-42 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablets, Oral, 0 mg, once daily, 16 weeks
Primary Outcome Measure Information:
Title
Percentage of Patients Relapsing by Week 16
Description
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.
Time Frame
From end of Phase 1 (Date of randomization) to Week 16 of Phase 2 and end of treatment
Secondary Outcome Measure Information:
Title
Adjusted Mean Change From Baseline to Week 16 on the Aberrant Behavior Checklist Irritability (ABC-I) Subscale Score (Last Observation Carried Forward [LOCF])
Description
ABC is an informant-based checklist used to assess and classify problem behaviors of children and adolescents with mental retardation. The 58 items are rated on a 4-point scale (0=not at all a problem to 3=the problem is severe in degree), and resolve into 5 subscales: 1) irritability, agitation; 2) lethargy, social withdrawal; 3) stereotypic behavior; 4) hyperactivity, noncompliance; and 5) inappropriate speech. The ABC can be completed by parents, special educators, psychologists, direct caregivers, nurses, and others knowing the participant. Psychometric assessment of the ABC indicates that its subscales have high internal consistency, adequate reliability, and established validity. The ABC-I Subscale Score ranges from 0 to 45, with a negative change in score signifying improvement. LOCF data set includes data recorded at a given visit or, if no observation was recorded at that visit, data carried forward from the prior visit. chg=change; BL=baseline; APR=aripiprazole; vs=versus.
Time Frame
From Baseline (end of Phase 1) to Week 16 of Phase 2
Title
Change From Baseline in Mean Clinical Global Impression Improvement (CGI-I) Scale Score at Week 16 (Last Observation Carried Forward [LOCF])
Description
CG-I rating scale permits global evaluation of patient's improvement over time. At baseline (BL), CGI Severity of Illness assessment is performed, in which the clinician rates severity of patient's condition on a 7-point scale ranging from 1=no symptoms to 7=very severe symptoms. Higher total score=worse symptoms. At subsequent visits, clinician assesses patient's improvement relative to symptoms at baseline on CGI-I 7-point scale ranging from 1=very much improved to 7=very much worse. Since the drug targets irritability symptoms, the CGI focuses on severity of irritability secondary to autistic disorder. Lower score=more improved symptoms. LOCF data set includes data recorded at a given visit or, if nothing recorded, data areccarried forward from the prior visit. For secondary endpoints (endpt), hierarchical testing was used to keep overall experiment-wise type I error rate to <=0.05. diff=difference; IS=irritability scale; PA=primary analysis; signif=significance/significantly.
Time Frame
From Baseline (end of Phase 1) to Week 16 of Phase 2
Title
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Discontinuation During Phase 1
Description
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time Frame
Weekly from Week 1 to Week 26 and continuously to end of treatment
Other Pre-specified Outcome Measures:
Title
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs During Phase 2
Description
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Time Frame
Weekly from Weeks 1 through 16 (end of treatment) of Phase 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Harmonex Neuroscience Research, Inc
City
Dothan
State/Province
Alabama
ZIP/Postal Code
36303
Country
United States
Facility Name
Southwest Autism Research And Resource Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Clinical Innovations, Inc.
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92626
Country
United States
Facility Name
Behavioral Research Specialists, Llc
City
Glendale
State/Province
California
ZIP/Postal Code
91206
Country
United States
Facility Name
Abbey Neuropsychology Clinic
City
Palo Alto
State/Province
California
ZIP/Postal Code
94306
Country
United States
Facility Name
Ucsf - Lppi
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University School Of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Children'S National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Sarkis Clinical Trials
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
Facility Name
Palm Springs Research Institute
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Florida Clinical Research Center, Llc
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Facility Name
Miami Children'S Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
University Of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Institute For Behavioral Medicine, Llc
City
Smyrna
State/Province
Georgia
ZIP/Postal Code
30080
Country
United States
Facility Name
Kootenai Behavioral Health Center
City
Coeur D'Alene
State/Province
Idaho
ZIP/Postal Code
83814
Country
United States
Facility Name
Kosair Charities Pediatric Clinical Research Unit
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Lsu Health Sciences Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
Neurocare, Inc.
City
Newton
State/Province
Massachusetts
ZIP/Postal Code
02459
Country
United States
Facility Name
Neurobehavioral Medicine Group
City
Bloomfield Hills
State/Province
Michigan
ZIP/Postal Code
48302
Country
United States
Facility Name
Center For Psychiatry And Behavioral Medicine, Inc
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Clinical Research Center Of New Jersey
City
Gibbsboro
State/Province
New Jersey
ZIP/Postal Code
08026
Country
United States
Facility Name
Children'S Specialized Hosp
City
Toms River
State/Province
New Jersey
ZIP/Postal Code
08755
Country
United States
Facility Name
Stony Brook University School Of Medicine
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Unc Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27517
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44104
Country
United States
Facility Name
University Hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
The Ohio State University Nisonger Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Cutting Edge Research Group
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73116
Country
United States
Facility Name
Ou Physician'S Child Study Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73117
Country
United States
Facility Name
Tulsa Clinical Research, Llc
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74104
Country
United States
Facility Name
Cyn3rgy Research
City
Gresham
State/Province
Oregon
ZIP/Postal Code
97030
Country
United States
Facility Name
Drexel University College Of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19124
Country
United States
Facility Name
Western Psychiatric Institute And Clinic
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15203
Country
United States
Facility Name
Holston Medical Group
City
Kingsport
State/Province
Tennessee
ZIP/Postal Code
37660
Country
United States
Facility Name
Insite Clinical Research
City
Desoto
State/Province
Texas
ZIP/Postal Code
75115
Country
United States
Facility Name
Ericksen Research And Development
City
Clinton
State/Province
Utah
ZIP/Postal Code
84015
Country
United States
Facility Name
Childrens Specialty Gr., Pllc
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States
Facility Name
Virginia Treatment Center For Children
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24502859
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.
Results Reference
derived
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Phase IV Long-term Maintenance Study of Aripiprazole in the Treatment of Irritability Associated With Autistic Disorder
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