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

NCT00365859 | Completed Phase 3 Results DMC

• 1 other identifier: CN138-180
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 55

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 \[NCT00337571\]).

Conditions

Autistic Disorder; Behavioral Symptoms

Keywords

Serious behavioral problems in children and adolescents with AD; behavioral problems

Outcome Measures

Primary Outcomes (13)

• 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.

  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

• 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.

  Baseline, Week 8, Week 26, Week 52

• 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.

  Baseline, Week 8, Week 26, Week 52

• 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.

  Baseline, Week 8, Week 26, Week 52

• 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)

  At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52

• 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

  At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52

• 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

  At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52

• 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"

  At screening (up to 42 days prior to treatment start), Week 8, Week 26, Week 52

• 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).

  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 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 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).

  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 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.

  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 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).

  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 Outcomes (8)

• Mean Change From Baseline in Clinical Global Impression (CGI)-Severity Score at Week 52 (Endpoint, LOCF)

  Week 0 (Baseline), Week 52 (Endpoint, LOCF)

• CGI-Improvement Score at Week 52 (Endpoint, LOCF)

  Week 52 (Endpoint, LOCF)

• Mean Change From Baseline in Aberrant Behavior Checklist (ABC) Irritability Score at Week 52 (Endpoint, LOCF)

  Week 0 (Baseline), Week 52 (Endpoint, LOCF)

• Mean Change From Baseline in ABC Hyperactivity Subscale Score at Week 52 (Endpoint, LOCF)

  Week 0 (Baseline), Week 52 (Endpoint, LOCF)

• Change From Baseline in ABC Stereotypy Subscale Score at Week 52 (Endpoint, LOCF)

  Week 0 (Baseline), Week 52 (Endpoint, LOCF)

Study Arms (3)

De Novo

EXPERIMENTAL

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.

Drug: Aripiprazole

Rollover Placebo

EXPERIMENTAL

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.

Drug: Aripiprazole

Rollover Aripiprazole

EXPERIMENTAL

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.

Drug: Aripiprazole

Interventions

Aripiprazole DRUG

Tablets, Oral, 2, 5, 10, or 15 mg, once daily, 52 weeks

Also known as: Abilify, BMS-337039

De Novo; Rollover Aripiprazole; Rollover Placebo

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• Otsuka America Pharmaceutical: collaborator

Study Sites (55)

University of Alabama at Birmingham

Birmingham, Alabama, 35203, United States

Location

Harmonex Neuroscience

Dothan, Alabama, 36303, United States

Location

Southwest Autism Research and Resource Center

Phoenix, Arizona, 85006, United States

Location

Univ of Arizona

Tuscon, Arizona, 85724-5002, United States

Location

Clinical Innovations, Inc

Costa Mesa, California, 92626, United States

Location

Peninsula Research Assoc

Rolling Hills Estate, California, 90274, United States

Location

University Of California-Davis Health Science Center

Sacramento, California, 95817, United States

Location

Sharp Mesa Vista Hospital

San Diego, California, 92123, United States

Location

Stanford University School Of Medicine

Stanford, California, 94305-5719, United States

Location

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

Offices of Gregory Marsella, MD, PA

Boca Raton, Florida, 33432, United States

Location

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Children's Developmental Center

Winter Park, Florida, 32792, United States

Location

Child Neurology Associates, PC

Atlanta, Georgia, 30342, United States

Location

Institute For Behavioral Medicine

Smyrna, Georgia, 30080-6342, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60608, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Massachusetts General Hospital

Cambridge, Massachusetts, 02138, United States

Location

Cambridge Health Alliance

Cambridge, Massachusetts, 02139, United States

Location

Ladders Clinic

Wellsley, Massachusetts, 02481, United States

Location

Neurobehavioral Medicine Group

Bloomfield Hills, Michigan, 48302, United States

Location

Children's Hospital Of Michigan

Detroit, Michigan, 48201, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Children's Mercy Hospital and Clinics

Kansas City, Missouri, 64108-4619, United States

Location

Munroe-Meyer Institute Diagnostic Center

Omaha, Nebraska, 68198-5380, United States

Location

Center for Psychiatry and Behavioral Medicine

Las Vegas, Nevada, 89128, United States

Location

Children's Specialized Hospital

Toms River, New Jersey, 08755, United States

Location

North Shore - Long Island Jewish Health System

Bethpage, New York, 11714, United States

Location

Seaver and New York Autism Center of Excellence

New York, New York, 10029, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

SUNY at Stony Brook - School of Medicine

Stony Brook, New York, 11794-8790, United States

Location

Mission Hospitals - Mission Children's Clinics

Asheville, North Carolina, 22801, United States

Location

University of NC

Chapel Hill, North Carolina, 27599-7160, United States

Location

Duke Child and Family Study Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267-0559, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

The Nisonger Center

Columbus, Ohio, 43210, United States

Location

Cutting Edge Research

Oklahoma City, Oklahoma, 73116, United States

Location

Western Psychiatric Institute and Clinic

Pittsburgh, Pennsylvania, 15203, United States

Location

UT Medical Group, Department Of Psychiatry

Memphis, Tennessee, 38105, United States

Location

Dallas Pediatric Neurology Associates

Dallas, Texas, 75230, United States

Location

Bayou City Research, Ltd.

Houston, Texas, 77007, United States

Location

Red Oak Psychiatry Associates, PA

Houston, Texas, 77090, United States

Location

North San Antonio Healthcare Associates

San Antonio, Texas, 78218, United States

Location

Children's National Medical Center

Fairfax, Virginia, 22031, United States

Location

Neuroscience, Inc

Herndon, Virginia, 20170, United States

Location

Monarch Research Associates

Norfolk, Virginia, 23510, United States

Location

Virginia Treatment Center For Children

Richmond, Virginia, 23298, United States

Location

Pacific Institute of Medical Sciences

Bothell, Washington, 98034, United States

Location

Autism Spectrum Treatment and Research Center

Seattle, Washington, 98109, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (3)

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

  PMID: 37811711 DERIVED

• 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.

  PMID: 21813076 DERIVED

• 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.

  PMID: 21663425 DERIVED

Related Links

• Investigator Inquiry form
• Centers for Disease Control and Prevention (CDC) algorithm for BMI and body weight z-scores

MeSH Terms

Conditions

Autistic Disorder; Behavioral Symptoms; Problem Behavior

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Behavior; Child Behavior

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

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

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 15, 2006
• First Posted: August 18, 2006
• Study Start: September 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: December 2, 2013
• Results First Posted: January 25, 2010

Record last verified: 2010-06

Locations

US (55)