Study of Aripiprazole in the Treatment of Serious Behavioral Problems in Children and Adolescents With Autistic Disorder (AD)
- Registration Number
- NCT00365859
- 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 \[NCT00337571\]).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 330
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description De Novo Aripiprazole 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. Rollover Placebo Aripiprazole 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. Rollover Aripiprazole Aripiprazole 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (AEs), Deaths, AEs Leading to Discontinuation, Extra Pyramidal Syndrome (EPS)-Related AEs 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 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 Patient Weight 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) Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Week 8, Week 26, Week 52, and Endpoint Baseline, Week 8, Week 26, Week 52 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 At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52 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 At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52 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 Eletrocardiograph (ECG) Abnormalities At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52 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 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) 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 by Time Period in Body Weight Z-Score 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) 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 Total Simpson-Angus Scale (SAS) At Week 8, Week 26, and Week 52 Baseline, Week 8, Week 26, 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 Baseline, Week 8, Week 26, 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.
Number of Participants With Potentially Clinically Relevant Laboratory Chemistry Abnormalities At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52 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
Mean Change From Baseline in Patient Body Mass Index (BMI) 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) 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 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) 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
Name Time Method Mean Change From Baseline in ABC Social Withdrawal Scale At Week 52 (Endpoint, LOCF) Week 0 (Baseline), 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 Clinical Global Impression (CGI)-Severity Score at Week 52 (Endpoint, LOCF) Week 0 (Baseline), 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) 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) Week 0 (Baseline), 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) Week 0 (Baseline), 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) Week 0 (Baseline), 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 Inappropriate Speech Subscale Score at Week 52 (Endpoint, LOCF) Week 0 (Baseline), 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) Week 0 (Baseline), 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.
Trial Locations
- Locations (55)
Institute For Behavioral Medicine
🇺🇸Smyrna, Georgia, United States
Regions Hospital
🇺🇸St. Paul, Minnesota, United States
Harmonex Neuroscience
🇺🇸Dothan, Alabama, United States
Richmond Behavioral Associates
🇺🇸Staten Island, New York, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Western Psychiatric Institute and Clinic
🇺🇸Pittsburgh, Pennsylvania, United States
Clinical Innovations, Inc
🇺🇸Costa Mesa, California, United States
Miami Children's Hospital
🇺🇸Miami, Florida, United States
Offices of Gregory Marsella, MD, PA
🇺🇸Boca Raton, Florida, United States
Children's Developmental Center
🇺🇸Winter Park, Florida, United States
Bayou City Research, Ltd.
🇺🇸Houston, Texas, United States
Red Oak Psychiatry Associates, PA
🇺🇸Houston, Texas, United States
Autism Spectrum Treatment and Research Center
🇺🇸Seattle, Washington, United States
Sharp Mesa Vista Hospital
🇺🇸San Diego, California, United States
Duke Child and Family Study Center
🇺🇸Durham, North Carolina, United States
North San Antonio Healthcare Associates
🇺🇸San Antonio, Texas, United States
Kansas University Medical Center
🇺🇸Kansas City, Kansas, United States
Southwest Autism Research and Resource Center
🇺🇸Phoenix, Arizona, United States
Children's Hospital Of Michigan
🇺🇸Detroit, Michigan, United States
Cutting Edge Research
🇺🇸Oklahoma City, Oklahoma, United States
UT Medical Group, Department Of Psychiatry
🇺🇸Memphis, Tennessee, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
The Nisonger Center
🇺🇸Columbus, Ohio, United States
Virginia Treatment Center For Children
🇺🇸Richmond, Virginia, United States
Peninsula Research Assoc
🇺🇸Rolling Hills Estate, California, United States
Sarkis Clinical Trials
🇺🇸Gainesville, Florida, United States
North Shore - Long Island Jewish Health System
🇺🇸Bethpage, New York, United States
Children's Specialized Hospital
🇺🇸Toms River, New Jersey, United States
Seaver and New York Autism Center of Excellence
🇺🇸New York, New York, United States
Neuroscience, Inc
🇺🇸Herndon, Virginia, United States
Children's National Medical Center
🇺🇸Fairfax, Virginia, United States
Monarch Research Associates
🇺🇸Norfolk, Virginia, United States
SUNY at Stony Brook - School of Medicine
🇺🇸Stony Brook, New York, United States
Child Neurology Associates, PC
🇺🇸Atlanta, Georgia, United States
Mission Hospitals - Mission Children's Clinics
🇺🇸Asheville, North Carolina, United States
Pacific Institute of Medical Sciences
🇺🇸Bothell, Washington, United States
Dallas Pediatric Neurology Associates
🇺🇸Dallas, Texas, United States
University Of California-Davis Health Science Center
🇺🇸Sacramento, California, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
The Children's Hospital
🇺🇸Aurora, Colorado, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Munroe-Meyer Institute Diagnostic Center
🇺🇸Omaha, Nebraska, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Massachusetts General Hospital
🇺🇸Cambridge, Massachusetts, United States
Center for Psychiatry and Behavioral Medicine
🇺🇸Las Vegas, Nevada, United States
Ladders Clinic
🇺🇸Wellsley, Massachusetts, United States
Univ of Arizona
🇺🇸Tuscon, Arizona, United States
University of Florida
🇺🇸Gainesville, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Neurobehavioral Medicine Group
🇺🇸Bloomfield Hills, Michigan, United States
Cambridge Health Alliance
🇺🇸Cambridge, Massachusetts, United States
Children's Mercy Hospital and Clinics
🇺🇸Kansas City, Missouri, United States
University of NC
🇺🇸Chapel Hill, North Carolina, United States
Stanford University School Of Medicine
🇺🇸Stanford, California, United States