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

Browse trials for

• Autistic Disorder 1,030
• Behavioral Symptoms 135
• Problem Behavior 178

Keywords

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

Autistic Disorder

1,030 studies on the registry are indexed under Autistic Disorder; 266 are open to participants now.

This study's enrollment of 330 is above the median of 49 across 811 interventional studies indexed under Autistic Disorder.

Lead sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc. is the lead sponsor of 295 studies on the registry; 18 are open to participants now.

Of its 106 completed or terminated interventional studies of FDA-regulated products, 71 (67%) have results posted.

Study arms

• Experimental
  De Novo

  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

• Experimental
  Rollover Placebo

  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

• Experimental
  Rollover 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.

  Drug: Aripiprazole

Interventions

• DrugAripiprazole

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

  Also known as: Abilify, BMS-337039

Primary outcomes

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.

   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

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.

   Time frame: 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.

   Time frame: 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.

   Time frame: 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)

   Time frame: 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

   Time frame: 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

   Time frame: 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"

   Time frame: 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).

   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)

10. 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)

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.

    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)

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.

    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)

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.

    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 outcomes

1. 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.

   Time frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)

2. 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.

   Time frame: Week 52 (Endpoint, LOCF)

3. 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

   Time frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)

4. 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.

   Time frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)

5. 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.

   Time frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)

6. 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.

   Time frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)

7. 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.

   Time frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)

8. 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.

   Time frame: Week 0 (Baseline), Week 52 (Endpoint, LOCF)

Baseline characteristics

Publications

• 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. PubMed 37811711 ↗
• 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. PubMed 21813076 ↗
• 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. PubMed 21663425 ↗

Related links

• Otsuka Clinical Trial Website ↗
• Otsuka Clinical Trial Transparency ↗

Individual participant data

Plan to share: Yes — Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form

Time frame: Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.

Access criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Data sharing details ↗ · clinical-trials.otsuka.com