search
Back to results

Study of Aripiprazole in the Treatment of Serious Behavioral Problems in Children and Adolescents With Autistic Disorder (AD)

Primary Purpose

Autistic Disorder, Behavioral Symptoms

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Aripiprazole
Sponsored by
Otsuka Pharmaceutical Development & Commercialization, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autistic Disorder focused on measuring Serious behavioral problems in children and adolescents with AD, behavioral problems

Eligibility Criteria

6 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • Harmonex Neuroscience
  • Southwest Autism Research and Resource Center
  • Univ of Arizona
  • Clinical Innovations, Inc
  • Peninsula Research Assoc
  • University Of California-Davis Health Science Center
  • Sharp Mesa Vista Hospital
  • Stanford University School Of Medicine
  • The Children's Hospital
  • Offices of Gregory Marsella, MD, PA
  • Sarkis Clinical Trials
  • University of Florida
  • Miami Children's Hospital
  • University of South Florida
  • Children's Developmental Center
  • Child Neurology Associates, PC
  • Institute For Behavioral Medicine
  • University of Illinois at Chicago
  • Kansas University Medical Center
  • University of Louisville
  • Massachusetts General Hospital
  • Cambridge Health Alliance
  • Ladders Clinic
  • Neurobehavioral Medicine Group
  • Children's Hospital Of Michigan
  • Regions Hospital
  • Children's Mercy Hospital and Clinics
  • Munroe-Meyer Institute Diagnostic Center
  • Center for Psychiatry and Behavioral Medicine
  • Children's Specialized Hospital
  • North Shore - Long Island Jewish Health System
  • Seaver and New York Autism Center of Excellence
  • Richmond Behavioral Associates
  • SUNY at Stony Brook - School of Medicine
  • Mission Hospitals - Mission Children's Clinics
  • University of NC
  • Duke Child and Family Study Center
  • University of Cincinnati
  • University Hospitals of Cleveland
  • The Nisonger Center
  • Cutting Edge Research
  • Western Psychiatric Institute and Clinic
  • UT Medical Group, Department Of Psychiatry
  • Dallas Pediatric Neurology Associates
  • Bayou City Research, Ltd.
  • Red Oak Psychiatry Associates, PA
  • North San Antonio Healthcare Associates
  • Children's National Medical Center
  • Neuroscience, Inc
  • Monarch Research Associates
  • Virginia Treatment Center For Children
  • Pacific Institute of Medical Sciences
  • Autism Spectrum Treatment and Research Center
  • Children's Hospital of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

De Novo

Rollover Placebo

Rollover Aripiprazole

Arm Description

De novo participants (those who did not participate in protocol (CN138-178 [NCT00332241] or CN138-179 [NCT00337571]) assigned to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.

Participants who completed participation in protocol (CN138-178 [NCT00332241] or CN138-179 [NCT00337571]) on placebo treatment and continued to meet all of the inclusion criteria and none of the exclusion criteria. Assigned in this study to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.

Participants who completed participation in protocol CN138-178 [NCT00332241] or CN138-179 [NCT00337571] on aripiprazole treatment and continued to meet all of the inclusion criteria and none of the exclusion criteria. Assigned in this study to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.

Outcomes

Primary Outcome Measures

Number of Participants With Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (AEs), Deaths, AEs Leading to Discontinuation, Extra Pyramidal Syndrome (EPS)-Related AEs
Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Mean Change From Baseline in Total Simpson-Angus Scale (SAS) At Week 8, Week 26, and Week 52
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50. Negative change scores indicate improvement.
Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) At Week 8, Week 26, and Week 52
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Week 8, Week 26, Week 52, and Endpoint
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Number of Participants With Potentially Clinically Relevant Laboratory Metabolic Abnormalities
Abnormal metabolic criterion values include the following: fasting serum glucose ≥115 mg/dL; non-fasting serum glucose ≥ 200 mg/dL; total cholesterol ≥240 mg/dL; LDL cholesterol ≥160 mg/dL; HDL cholesterol ≤30 mg/dL; triglycerides ≥120 mg/dL (females), ≥160 mg/dL (males)
Number of Participants With Potentially Clinically Relevant Laboratory Hematology Abnormalities
Abnormal hematology criterion values include the following: hematocrit (ages 6-17, males & females) ≤33%; hemoglobin (ages 6-17, males & females) <11.3 g/dL; leukocytes ≤2800 c/mm3 or ≥16000 c/mm3; eosinophils (ages 6-17, males & females) >17%; neutrophils <15%; platelet count ≤75,000 c/mm3 or ≥700,000 c/mm3
Number of Participants With Potentially Clinically Relevant Laboratory Chemistry Abnormalities
Abnormal chemistry criterion values include the following: aspartate aminotransferase ≥3x upper limit of normal (ULN); alanine aminotransferase ≥3x ULN; alkaline phosphatase ≥3x ULN; lactate dehydrogenase ≥3x ULN; creatinine ≥2.0 mg/dL; uric acid, ≥10.5 mg/dL (male), ≥8.5 mg/dL (female); bilirubin (Total) ≥2.0 mg/dL; serum prolactin >ULN; creatine kinase ≥3x ULN; blood urea nitrogen ≥30 mg/dL; sodium ≤126 mEq/L or ≥156 mEq/L; potassium ≤2.5 mEq/L or ≥ 6.5 mEq/L; chloride ≤90 mEq/L or ≥118 mEq/L; calcium ≤8.2 mg/dL or ≥12 mg/dL
Number of Participants With Potentially Clinically Relevant Eletrocardiograph (ECG) Abnormalities
These abbreviations are used in the table of ECG measurements: supraventricular (SV), baseline (BL), 1 degree (1°), atrioventricular (A-V), intraventricular (IVT), symmetrical (SYM), corrected QT interval (QTc). QRS complex is a recording of a single heartbeat on ECG corresponding to the depolarization of the right and left ventricles. PR interval is measured from beginning of P wave to beginning of QRS complex. QT interval is a measure of time between start of Q wave and end of T wave in the heart's electrical cycle. ↑ = increase from baseline, ↓ = decrease from baseline, → = "to"
Number of Potentially Clinically Relevant Vital Sign Abnormalities
Clinically significantly abnormal vital signs met age-appropriate (heart rate cohorts: ages 5-14 & ages 15+; blood pressure cohorts: ages 6-12 & ages 13-17) criterion AND represented change from pretreatment value of at least the following magnitudes: systolic blood pressure (≥130 mmHg & ≥144 mmHg w/ increase of ≥20 mmHg) or (≤117 mmHg & ≤120 mmHg w/ decrease of ≥20 mmHg); diastolic blood pressure (≥86 mmHg & ≥92 mmHg w/ increase of ≥15 mmHg) or (≤75 mm Hg & ≤80 mmHg w/ decrease of ≥15 mmHg); heart rate (140 bpm and 120 bpm w/ increase of ≥15 bpm) or (50 bpm and 50 bpm w/ decrease of ≥15 bpm).
Mean Change From Baseline in Patient Weight
Mean Change From Baseline by Time Period in Body Weight Z-Score
The Z-Score indicates how many standard deviations a person is from the population norm values. The body weight z-scores are designed to take into account the amount of weight gain that would be expected due to normal growth in children and adolescents. The body weight z-scores are by age and gender standardized values (corresponding to a normal distribution with mean 0 and a standard deviation of 1) of the actual weight measurements, based on the Growth Charts provided by the Centers for Disease Control (CDC; see Links section of this record).
Mean Change From Baseline in Patient Body Mass Index (BMI)
The body mass index (BMI) is a statistical measurement which compares a person's weight and height. Though it does not actually measure the percentage of body fat, it is used to estimate a healthy body weight based on subject height.
Mean Change From Baseline By Time Period in BMI Z-Score
The Z-Score indicates how many standard deviations a person is from the population norm values. The BMI z-scores are designed to take into account the BMI that would be expected due to normal growth in children and adolescents. The BMI z-scores are by age and gender standardized values (corresponding to a normal distribution with mean 0 and a standard deviation of 1) of the actual BMI measurements, based on the Growth Charts provided by the Centers for Disease Control (CDC; see Links section of this record).

Secondary Outcome Measures

Mean Change From Baseline in Clinical Global Impression (CGI)-Severity Score at Week 52 (Endpoint, LOCF)
CGI scale is a global evaluation of improvement over time. CGI-Severity (CGI-S) is a clinician-rated assessment that evaluates the severity of a patient's condition on a 7-point scale ranging from 1 (no symptoms) to 7 (very severe symptoms). CGI-Severity score is from 1 to 7. A negative change score signifies improvement.
CGI-Improvement Score at Week 52 (Endpoint, LOCF)
CGI scale is a global evaluation of improvement over time. CGI-Improvement (CGI-I) is a clinician rated assessment that evaluates improvement relative to symptoms at baseline on a a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). CGI-I Score is from 1 to 7. A lower score signifies larger improvement.
Mean Change From Baseline in Aberrant Behavior Checklist (ABC) Irritability Score at Week 52 (Endpoint, LOCF)
The ABC is an informant-based symptom checklist for assessing and classifying 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 and agitation; (2) lethargy and social withdrawal; (3) stereotypic behavior; (4) hyperactivity and noncompliance, and (5) inappropriate speech. ABC Irritability Subscale Score is from 0 to 45. A negative change signifies improvement
Mean Change From Baseline in ABC Hyperactivity Subscale Score at Week 52 (Endpoint, LOCF)
The ABC is an informant-based symptom checklist for assessing and classifying 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 and agitation; (2) lethargy and social withdrawal; (3) stereotypic behavior; (4) hyperactivity and noncompliance, and (5) inappropriate speech. ABC Hyperactivity Subscale Score is from 0 to 48. A negative change score signifies improvement.
Change From Baseline in ABC Stereotypy Subscale Score at Week 52 (Endpoint, LOCF)
The ABC is an informant-based symptom checklist for assessing and classifying 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 and agitation; (2) lethargy and social withdrawal; (3) stereotypic behavior; (4) hyperactivity and noncompliance, and (5) inappropriate speech. ABC Stereotypy Subscale Score is from 0 to 21. A negative change score signifies improvement.
Mean Change From Baseline in ABC Social Withdrawal Scale At Week 52 (Endpoint, LOCF)
The ABC is an informant-based symptom checklist for assessing and classifying 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 and agitation; (2) lethargy and social withdrawal; (3) stereotypic behavior; (4) hyperactivity and noncompliance, and (5) inappropriate speech. ABC Social Withdrawal Subscale Score is from 0 to 48. A negative change score signifies improvement.
Mean Change From Baseline in ABC Inappropriate Speech Subscale Score at Week 52 (Endpoint, LOCF)
The ABC is an informant-based symptom checklist for assessing and classifying 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 and agitation; (2) lethargy and social withdrawal; (3) stereotypic behavior; (4) hyperactivity and noncompliance, and (5) inappropriate speech. ABC Inappropriate Speech Subscale score is from 1 to 12. A negative change score signifies improvement.
Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Score at Week 52 (Endpoint, LOCF)
CY-BOCS is a 10-item, clinician-rated scale designed to measure the severity of obsessive-compulsive symptoms in patients below the age of 18. The scale contains 5 items pertaining to obsessions (which were not used in this trial) and 5 items pertaining to compulsions, which rated each symptom domain in terms of time spent, interference with functioning, distress, resistance, and control. Each item was rated on a 5-point scale, from 0 (no symptoms or minimum severity) to 4 (extreme symptoms or maximum severity). CY-BOCS Score is from 0 to 20. A negative change score signifies improvement.

Full Information

First Posted
August 15, 2006
Last Updated
November 7, 2013
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
Otsuka America Pharmaceutical
search

1. Study Identification

Unique Protocol Identification Number
NCT00365859
Brief Title
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

2. Study Status

Record Verification Date
June 2010
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
Otsuka America Pharmaceutical

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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]).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autistic Disorder, Behavioral Symptoms
Keywords
Serious behavioral problems in children and adolescents with AD, behavioral problems

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
330 (Actual)

8. Arms, Groups, and Interventions

Arm Title
De Novo
Arm Type
Experimental
Arm Description
De novo participants (those who did not participate in protocol (CN138-178 [NCT00332241] or CN138-179 [NCT00337571]) assigned to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.
Arm Title
Rollover Placebo
Arm Type
Experimental
Arm Description
Participants who completed participation in protocol (CN138-178 [NCT00332241] or CN138-179 [NCT00337571]) on placebo treatment and continued to meet all of the inclusion criteria and none of the exclusion criteria. Assigned in this study to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.
Arm Title
Rollover Aripiprazole
Arm Type
Experimental
Arm Description
Participants who completed participation in protocol CN138-178 [NCT00332241] or CN138-179 [NCT00337571] on aripiprazole treatment and continued to meet all of the inclusion criteria and none of the exclusion criteria. Assigned in this study to open-label aripiprazole (oral tablet), flexibly dosed (2 to 15 mg/day) taken once daily, started at 2 mg/day on Day 1. Target daily dose was 5 mg, 10 mg, or 15 mg; maximum dose, regardless of weight, was 15 mg. Dose increases were incremental (dose levels are 2 mg, 5 mg, 10 mg, and 15 mg), occurring no more often than every 4 days, and were based on assessment of efficacy and tolerability at the current dose. The dosage could be adjusted downward if the patient experienced intolerance at any time to the current dose.
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Other Intervention Name(s)
Abilify, BMS-337039
Intervention Description
Tablets, Oral, 2, 5, 10, or 15 mg, once daily, 52 weeks
Primary Outcome Measure Information:
Title
Number of Participants With Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (AEs), Deaths, AEs Leading to Discontinuation, Extra Pyramidal Syndrome (EPS)-Related AEs
Description
Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time Frame
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
Title
Mean Change From Baseline in Total Simpson-Angus Scale (SAS) At Week 8, Week 26, and Week 52
Description
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50. Negative change scores indicate improvement.
Time Frame
Baseline, Week 8, Week 26, Week 52
Title
Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) At Week 8, Week 26, and Week 52
Description
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
Time Frame
Baseline, Week 8, Week 26, Week 52
Title
Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Week 8, Week 26, Week 52, and Endpoint
Description
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Time Frame
Baseline, Week 8, Week 26, Week 52
Title
Number of Participants With Potentially Clinically Relevant Laboratory Metabolic Abnormalities
Description
Abnormal metabolic criterion values include the following: fasting serum glucose ≥115 mg/dL; non-fasting serum glucose ≥ 200 mg/dL; total cholesterol ≥240 mg/dL; LDL cholesterol ≥160 mg/dL; HDL cholesterol ≤30 mg/dL; triglycerides ≥120 mg/dL (females), ≥160 mg/dL (males)
Time Frame
At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
Title
Number of Participants With Potentially Clinically Relevant Laboratory Hematology Abnormalities
Description
Abnormal hematology criterion values include the following: hematocrit (ages 6-17, males & females) ≤33%; hemoglobin (ages 6-17, males & females) <11.3 g/dL; leukocytes ≤2800 c/mm3 or ≥16000 c/mm3; eosinophils (ages 6-17, males & females) >17%; neutrophils <15%; platelet count ≤75,000 c/mm3 or ≥700,000 c/mm3
Time Frame
At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
Title
Number of Participants With Potentially Clinically Relevant Laboratory Chemistry Abnormalities
Description
Abnormal chemistry criterion values include the following: aspartate aminotransferase ≥3x upper limit of normal (ULN); alanine aminotransferase ≥3x ULN; alkaline phosphatase ≥3x ULN; lactate dehydrogenase ≥3x ULN; creatinine ≥2.0 mg/dL; uric acid, ≥10.5 mg/dL (male), ≥8.5 mg/dL (female); bilirubin (Total) ≥2.0 mg/dL; serum prolactin >ULN; creatine kinase ≥3x ULN; blood urea nitrogen ≥30 mg/dL; sodium ≤126 mEq/L or ≥156 mEq/L; potassium ≤2.5 mEq/L or ≥ 6.5 mEq/L; chloride ≤90 mEq/L or ≥118 mEq/L; calcium ≤8.2 mg/dL or ≥12 mg/dL
Time Frame
At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
Title
Number of Participants With Potentially Clinically Relevant Eletrocardiograph (ECG) Abnormalities
Description
These abbreviations are used in the table of ECG measurements: supraventricular (SV), baseline (BL), 1 degree (1°), atrioventricular (A-V), intraventricular (IVT), symmetrical (SYM), corrected QT interval (QTc). QRS complex is a recording of a single heartbeat on ECG corresponding to the depolarization of the right and left ventricles. PR interval is measured from beginning of P wave to beginning of QRS complex. QT interval is a measure of time between start of Q wave and end of T wave in the heart's electrical cycle. ↑ = increase from baseline, ↓ = decrease from baseline, → = "to"
Time Frame
At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52
Title
Number of Potentially Clinically Relevant Vital Sign Abnormalities
Description
Clinically significantly abnormal vital signs met age-appropriate (heart rate cohorts: ages 5-14 & ages 15+; blood pressure cohorts: ages 6-12 & ages 13-17) criterion AND represented change from pretreatment value of at least the following magnitudes: systolic blood pressure (≥130 mmHg & ≥144 mmHg w/ increase of ≥20 mmHg) or (≤117 mmHg & ≤120 mmHg w/ decrease of ≥20 mmHg); diastolic blood pressure (≥86 mmHg & ≥92 mmHg w/ increase of ≥15 mmHg) or (≤75 mm Hg & ≤80 mmHg w/ decrease of ≥15 mmHg); heart rate (140 bpm and 120 bpm w/ increase of ≥15 bpm) or (50 bpm and 50 bpm w/ decrease of ≥15 bpm).
Time Frame
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)
Title
Mean Change From Baseline in Patient Weight
Time Frame
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)
Title
Mean Change From Baseline by Time Period in Body Weight Z-Score
Description
The Z-Score indicates how many standard deviations a person is from the population norm values. The body weight z-scores are designed to take into account the amount of weight gain that would be expected due to normal growth in children and adolescents. The body weight z-scores are by age and gender standardized values (corresponding to a normal distribution with mean 0 and a standard deviation of 1) of the actual weight measurements, based on the Growth Charts provided by the Centers for Disease Control (CDC; see Links section of this record).
Time Frame
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)
Title
Mean Change From Baseline in Patient Body Mass Index (BMI)
Description
The body mass index (BMI) is a statistical measurement which compares a person's weight and height. Though it does not actually measure the percentage of body fat, it is used to estimate a healthy body weight based on subject height.
Time Frame
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)
Title
Mean Change From Baseline By Time Period in BMI Z-Score
Description
The Z-Score indicates how many standard deviations a person is from the population norm values. The BMI z-scores are designed to take into account the BMI that would be expected due to normal growth in children and adolescents. The BMI z-scores are by age and gender standardized values (corresponding to a normal distribution with mean 0 and a standard deviation of 1) of the actual BMI measurements, based on the Growth Charts provided by the Centers for Disease Control (CDC; see Links section of this record).
Time Frame
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 Outcome Measure Information:
Title
Mean Change From Baseline in Clinical Global Impression (CGI)-Severity Score at Week 52 (Endpoint, LOCF)
Description
CGI scale is a global evaluation of improvement over time. CGI-Severity (CGI-S) is a clinician-rated assessment that evaluates the severity of a patient's condition on a 7-point scale ranging from 1 (no symptoms) to 7 (very severe symptoms). CGI-Severity score is from 1 to 7. A negative change score signifies improvement.
Time Frame
Week 0 (Baseline), Week 52 (Endpoint, LOCF)
Title
CGI-Improvement Score at Week 52 (Endpoint, LOCF)
Description
CGI scale is a global evaluation of improvement over time. CGI-Improvement (CGI-I) is a clinician rated assessment that evaluates improvement relative to symptoms at baseline on a a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). CGI-I Score is from 1 to 7. A lower score signifies larger improvement.
Time Frame
Week 52 (Endpoint, LOCF)
Title
Mean Change From Baseline in Aberrant Behavior Checklist (ABC) Irritability Score at Week 52 (Endpoint, LOCF)
Description
The ABC is an informant-based symptom checklist for assessing and classifying 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 and agitation; (2) lethargy and social withdrawal; (3) stereotypic behavior; (4) hyperactivity and noncompliance, and (5) inappropriate speech. ABC Irritability Subscale Score is from 0 to 45. A negative change signifies improvement
Time Frame
Week 0 (Baseline), Week 52 (Endpoint, LOCF)
Title
Mean Change From Baseline in ABC Hyperactivity Subscale Score at Week 52 (Endpoint, LOCF)
Description
The ABC is an informant-based symptom checklist for assessing and classifying 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 and agitation; (2) lethargy and social withdrawal; (3) stereotypic behavior; (4) hyperactivity and noncompliance, and (5) inappropriate speech. ABC Hyperactivity Subscale Score is from 0 to 48. A negative change score signifies improvement.
Time Frame
Week 0 (Baseline), Week 52 (Endpoint, LOCF)
Title
Change From Baseline in ABC Stereotypy Subscale Score at Week 52 (Endpoint, LOCF)
Description
The ABC is an informant-based symptom checklist for assessing and classifying 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 and agitation; (2) lethargy and social withdrawal; (3) stereotypic behavior; (4) hyperactivity and noncompliance, and (5) inappropriate speech. ABC Stereotypy Subscale Score is from 0 to 21. A negative change score signifies improvement.
Time Frame
Week 0 (Baseline), Week 52 (Endpoint, LOCF)
Title
Mean Change From Baseline in ABC Social Withdrawal Scale At Week 52 (Endpoint, LOCF)
Description
The ABC is an informant-based symptom checklist for assessing and classifying 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 and agitation; (2) lethargy and social withdrawal; (3) stereotypic behavior; (4) hyperactivity and noncompliance, and (5) inappropriate speech. ABC Social Withdrawal Subscale Score is from 0 to 48. A negative change score signifies improvement.
Time Frame
Week 0 (Baseline), Week 52 (Endpoint, LOCF)
Title
Mean Change From Baseline in ABC Inappropriate Speech Subscale Score at Week 52 (Endpoint, LOCF)
Description
The ABC is an informant-based symptom checklist for assessing and classifying 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 and agitation; (2) lethargy and social withdrawal; (3) stereotypic behavior; (4) hyperactivity and noncompliance, and (5) inappropriate speech. ABC Inappropriate Speech Subscale score is from 1 to 12. A negative change score signifies improvement.
Time Frame
Week 0 (Baseline), Week 52 (Endpoint, LOCF)
Title
Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Score at Week 52 (Endpoint, LOCF)
Description
CY-BOCS is a 10-item, clinician-rated scale designed to measure the severity of obsessive-compulsive symptoms in patients below the age of 18. The scale contains 5 items pertaining to obsessions (which were not used in this trial) and 5 items pertaining to compulsions, which rated each symptom domain in terms of time spent, interference with functioning, distress, resistance, and control. Each item was rated on a 5-point scale, from 0 (no symptoms or minimum severity) to 4 (extreme symptoms or maximum severity). CY-BOCS Score is from 0 to 20. A negative change score signifies improvement.
Time Frame
Week 0 (Baseline), Week 52 (Endpoint, LOCF)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
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
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35203
Country
United States
Facility Name
Harmonex Neuroscience
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
Univ of Arizona
City
Tuscon
State/Province
Arizona
ZIP/Postal Code
85724-5002
Country
United States
Facility Name
Clinical Innovations, Inc
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92626
Country
United States
Facility Name
Peninsula Research Assoc
City
Rolling Hills Estate
State/Province
California
ZIP/Postal Code
90274
Country
United States
Facility Name
University Of California-Davis Health Science Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Sharp Mesa Vista Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Stanford University School Of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5719
Country
United States
Facility Name
The Children's Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Offices of Gregory Marsella, MD, PA
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33432
Country
United States
Facility Name
Sarkis Clinical Trials
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32607
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
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
Children's Developmental Center
City
Winter Park
State/Province
Florida
ZIP/Postal Code
32792
Country
United States
Facility Name
Child Neurology Associates, PC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Institute For Behavioral Medicine
City
Smyrna
State/Province
Georgia
ZIP/Postal Code
30080-6342
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60608
Country
United States
Facility Name
Kansas University Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Massachusetts General Hospital
City
Cambridge
State/Province
Massachusetts
ZIP/Postal Code
02138
Country
United States
Facility Name
Cambridge Health Alliance
City
Cambridge
State/Province
Massachusetts
ZIP/Postal Code
02139
Country
United States
Facility Name
Ladders Clinic
City
Wellsley
State/Province
Massachusetts
ZIP/Postal Code
02481
Country
United States
Facility Name
Neurobehavioral Medicine Group
City
Bloomfield Hills
State/Province
Michigan
ZIP/Postal Code
48302
Country
United States
Facility Name
Children's Hospital Of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Regions Hospital
City
St. Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Children's Mercy Hospital and Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108-4619
Country
United States
Facility Name
Munroe-Meyer Institute Diagnostic Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-5380
Country
United States
Facility Name
Center for Psychiatry and Behavioral Medicine
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Children's Specialized Hospital
City
Toms River
State/Province
New Jersey
ZIP/Postal Code
08755
Country
United States
Facility Name
North Shore - Long Island Jewish Health System
City
Bethpage
State/Province
New York
ZIP/Postal Code
11714
Country
United States
Facility Name
Seaver and New York Autism Center of Excellence
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Richmond Behavioral Associates
City
Staten Island
State/Province
New York
ZIP/Postal Code
10312
Country
United States
Facility Name
SUNY at Stony Brook - School of Medicine
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794-8790
Country
United States
Facility Name
Mission Hospitals - Mission Children's Clinics
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
22801
Country
United States
Facility Name
University of NC
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7160
Country
United States
Facility Name
Duke Child and Family Study Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267-0559
Country
United States
Facility Name
University Hospitals of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
The Nisonger Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Cutting Edge Research
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73116
Country
United States
Facility Name
Western Psychiatric Institute and Clinic
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15203
Country
United States
Facility Name
UT Medical Group, Department Of Psychiatry
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Dallas Pediatric Neurology Associates
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Bayou City Research, Ltd.
City
Houston
State/Province
Texas
ZIP/Postal Code
77007
Country
United States
Facility Name
Red Oak Psychiatry Associates, PA
City
Houston
State/Province
Texas
ZIP/Postal Code
77090
Country
United States
Facility Name
North San Antonio Healthcare Associates
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78218
Country
United States
Facility Name
Children's National Medical Center
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Neuroscience, Inc
City
Herndon
State/Province
Virginia
ZIP/Postal Code
20170
Country
United States
Facility Name
Monarch Research Associates
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
Facility Name
Pacific Institute of Medical Sciences
City
Bothell
State/Province
Washington
ZIP/Postal Code
98034
Country
United States
Facility Name
Autism Spectrum Treatment and Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21813076
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.
Results Reference
derived
PubMed Identifier
21663425
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.
Results Reference
derived
Links:
URL
http://www.cdc.gov/growthcharts/percentile_data_files.htm
Description
Centers for Disease Control and Prevention (CDC) algorithm for BMI and body weight z-scores

Learn more about this trial

Study of Aripiprazole in the Treatment of Serious Behavioral Problems in Children and Adolescents With Autistic Disorder (AD)

We'll reach out to this number within 24 hrs