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

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 6 to 17 years
• All sexes
• No healthy volunteers
• Child

Trial locations and contacts

55 sites in 1 country.

About this study

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

Conditions

Autistic Disorder, Behavioral Symptoms

Being tested

Aripiprazole

Keywords

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

Medical subject headings

Autistic Disorder, Behavioral Symptoms, Problem Behavior

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• AripiprazoleDrug

  Also called Abilify, BMS-337039

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

What is being measured

The primary outcome is the main question the study is designed to answer.

1. 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.

   Measured: 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

2. 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.

   Measured: Baseline, Week 8, Week 26, Week 52

3. 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.

   Measured: Baseline, Week 8, Week 26, Week 52

4. 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.

   Measured: Baseline, Week 8, Week 26, Week 52

5. 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)

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

6. 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

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

7. 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

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

8. 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"

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

9. 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).

   Measured: 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)

10. Mean Change From Baseline in Patient Weight

    Measured: 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)

11. 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). Subjects included in the period evaluation had a baseline and at least 1 measurement within the time period that was assessed. Patients are only counted once in each time period but can appear in multiple time periods. For those with multiple records in 1 time period, only the last record in that period is included in calculations.

    Measured: 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)

12. 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.

    Measured: 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)

13. 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). Subjects included in the period evaluation had a baseline and at least 1 measurement within the time period that was assessed. Patients are only counted once in each time period but can appear in multiple time periods. For those with multiple records in 1 time period, only the last record in that period is included in calculations.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted18 Aug 2006 (estimated)
2. Study start1 Sep 2006
3. Primary completion1 Jun 2009
4. Study completion1 Jun 2009

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Publications (3)Papers the sponsor has linked to this study.
• Other trials for Autistic DisorderStudies of the same condition, open and under way.
• More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.