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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01227668
First received: October 22, 2010
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Irritability Associated With Autistic Disorder
Drug: Aripiprazole
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Aripiprazole in the Long-term Maintenance Treatment of Pediatric Patients With Irritability Associated With Autistic Disorder

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Patients Relapsing by Week 16 [ Time Frame: From end of Phase 1 (Date of randomization) to Week 16 of Phase 2 and end of treatment ] [ Designated as safety issue: No ]
    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]) [ Time Frame: From Baseline (end of Phase 1) to Week 16 of Phase 2 ] [ Designated as safety issue: No ]
    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]) [ Time Frame: From Baseline (end of Phase 1) to Week 16 of Phase 2 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weekly from Week 1 to Week 26 and continuously to end of treatment ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs During Phase 2 [ Time Frame: Weekly from Weeks 1 through 16 (end of treatment) of Phase 2 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 215
Study Start Date: March 2011
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aripiprazole Drug: Aripiprazole
Tablets, Oral, 2-15 mg, once daily, 13-42 weeks
Other Names:
  • BMS-337039
  • Abilify
Placebo Comparator: Placebo Drug: Placebo
Tablets, Oral, 0 mg, once daily, 16 weeks

Detailed Description:

Phase 1: Single blind/ Phase 2: Double blind

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01227668

  Show 38 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01227668     History of Changes
Other Study ID Numbers: CN138-603
Study First Received: October 22, 2010
Results First Received: November 7, 2013
Last Updated: March 31, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Autistic Disorder
Disease
Child Development Disorders, Pervasive
Mental Disorders
Mental Disorders Diagnosed in Childhood
Pathologic Processes
Aripiprazole
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 20, 2014