Trial Outcomes & Findings for Study of Aripiprazole in the Treatment of Children and Adolescents With Autistic Disorder (AD) (NCT NCT00337571)
NCT ID: NCT00337571
Last Updated: 2013-12-02
Results Overview
The ABC is a 58-item informant-based assessment of problem behaviors in children/adolescents with mental retardation. Items are rated on a 4-point scale (0=no problem, 3=severe problem), and resolve into 5 domain subscales. A decrease in score indicates improvement.
COMPLETED
PHASE3
218 participants
Week 8
2013-12-02
Participant Flow
Participant milestones
| Measure |
Placebo
|
Aripiprazole 5 mg
|
Aripiprazole 10 mg
|
Aripiprazole 15 mg
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
52
|
53
|
59
|
54
|
|
Overall Study
COMPLETED
|
38
|
44
|
49
|
47
|
|
Overall Study
NOT COMPLETED
|
14
|
9
|
10
|
7
|
Reasons for withdrawal
| Measure |
Placebo
|
Aripiprazole 5 mg
|
Aripiprazole 10 mg
|
Aripiprazole 15 mg
|
|---|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
3
|
0
|
0
|
0
|
|
Overall Study
Adverse Event
|
4
|
5
|
8
|
4
|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
3
|
1
|
0
|
1
|
|
Overall Study
Poor/noncompliance
|
1
|
1
|
1
|
1
|
|
Overall Study
No longer met study criteria
|
1
|
0
|
0
|
0
|
|
Overall Study
High Potassium level
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Study of Aripiprazole in the Treatment of Children and Adolescents With Autistic Disorder (AD)
Baseline characteristics by cohort
| Measure |
Placebo
n=52 Participants
|
Aripiprazole 5 mg
n=53 Participants
|
Aripiprazole 10 mg
n=59 Participants
|
Aripiprazole 15 mg
n=54 Participants
|
Total
n=218 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
6 to 12 years
|
35 participants
n=5 Participants
|
44 participants
n=7 Participants
|
45 participants
n=5 Participants
|
42 participants
n=4 Participants
|
166 participants
n=21 Participants
|
|
Age, Customized
13 to 17 years
|
17 participants
n=5 Participants
|
9 participants
n=7 Participants
|
14 participants
n=5 Participants
|
12 participants
n=4 Participants
|
52 participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
23 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
50 Participants
n=4 Participants
|
195 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
0 participants
n=4 Participants
|
6 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
13 participants
n=5 Participants
|
13 participants
n=7 Participants
|
15 participants
n=5 Participants
|
9 participants
n=4 Participants
|
50 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
35 participants
n=5 Participants
|
37 participants
n=7 Participants
|
41 participants
n=5 Participants
|
42 participants
n=4 Participants
|
155 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
6 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Hispanic/Latino
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic/Latino
|
44 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
193 Participants
n=21 Participants
|
|
Weight Group
<40 kilograms
|
24 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
126 Participants
n=21 Participants
|
|
Weight Group
≥40 kilograms
|
28 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
92 Participants
n=21 Participants
|
|
Body Mass Index
|
20.49 kg/m2
STANDARD_DEVIATION 4.777 • n=5 Participants
|
19.91 kg/m2
STANDARD_DEVIATION 6.124 • n=7 Participants
|
21.06 kg/m2
STANDARD_DEVIATION 6.649 • n=5 Participants
|
20.14 kg/m2
STANDARD_DEVIATION 6.033 • n=4 Participants
|
20.41 kg/m2
STANDARD_DEVIATION 5.933 • n=21 Participants
|
|
Height
|
144.9 centimeters
STANDARD_DEVIATION 18.82 • n=5 Participants
|
136.5 centimeters
STANDARD_DEVIATION 14.66 • n=7 Participants
|
142.3 centimeters
STANDARD_DEVIATION 17.87 • n=5 Participants
|
139.3 centimeters
STANDARD_DEVIATION 17.24 • n=4 Participants
|
140.8 centimeters
STANDARD_DEVIATION 17.38 • n=21 Participants
|
|
Weight
|
45.6 kilograms
STANDARD_DEVIATION 20.01 • n=5 Participants
|
38.9 kilograms
STANDARD_DEVIATION 18.26 • n=7 Participants
|
44.8 kilograms
STANDARD_DEVIATION 22.38 • n=5 Participants
|
42.2 kilograms
STANDARD_DEVIATION 22.99 • n=4 Participants
|
42.9 kilograms
STANDARD_DEVIATION 21.07 • n=21 Participants
|
PRIMARY outcome
Timeframe: Week 8Population: Efficacy population=all randomized participants minus 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.
The ABC is a 58-item informant-based assessment of problem behaviors in children/adolescents with mental retardation. Items are rated on a 4-point scale (0=no problem, 3=severe problem), and resolve into 5 domain subscales. A decrease in score indicates improvement.
Outcome measures
| Measure |
Placebo
n=49 Participants
|
Aripiprazole 5 mg
n=52 Participants
|
Aripiprazole 10 mg
n=59 Participants
|
Aripiprazole 15 mg
n=53 Participants
|
|---|---|---|---|---|
|
Mean Change (Week 8 - Baseline) in the Autistic Behavior Checklist (ABC) Irritability Subscale Score
|
-8.4 units on a scale
Standard Error 1.39
|
-12.4 units on a scale
Standard Error 1.36
|
-13.2 units on a scale
Standard Error 1.25
|
-14.4 units on a scale
Standard Error 1.31
|
SECONDARY outcome
Timeframe: Week 8Population: Efficacy population=all randomized participants minus 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.
The CGI scale is a clinician-rated global assessment of a patient's improvement over time. Baseline assessment rated a patient's condition on a 7-point scale (1=no symptoms, 7=very severe symptoms). Subsequent assessed improvement relative to baseline symptoms on a 7-point CGI-I item scale (1=very much improved, 7=very much worse).
Outcome measures
| Measure |
Placebo
n=49 Participants
|
Aripiprazole 5 mg
n=52 Participants
|
Aripiprazole 10 mg
n=59 Participants
|
Aripiprazole 15 mg
n=53 Participants
|
|---|---|---|---|---|
|
Mean Clinical Global Impressions Improvement Scale (CGI-I) Score
|
3.3 units on a scale
Standard Error 0.18
|
2.6 units on a scale
Standard Error 0.17
|
2.5 units on a scale
Standard Error 0.16
|
2.5 units on a scale
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Week 8Population: Efficacy population=all randomized participants minus 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.
Response defined as a ≥ 25% reduction from baseline to endpoint in the ABC Irritability Subscale score and a CGI-I score of 1 or 2 at endpoint.
Outcome measures
| Measure |
Placebo
n=49 Participants
|
Aripiprazole 5 mg
n=52 Participants
|
Aripiprazole 10 mg
n=59 Participants
|
Aripiprazole 15 mg
n=53 Participants
|
|---|---|---|---|---|
|
Number of Participants With Response at Week 8
|
17 Participants
|
29 Participants
|
29 Participants
|
28 Participants
|
SECONDARY outcome
Timeframe: Week 8Population: Efficacy population=all randomized participants minus 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.
CY-BOCS=10-item assessment of obsessive-compulsive symptoms in patients \<18 years. 5 items pertaining to compulsions rate symptoms (time spent, interference with functioning, distress, resistance, control) on a 5-point scale (0=no symptoms/minimum severity, 4=extreme symptoms/maximum severity). A decreased in value indicates improvement.
Outcome measures
| Measure |
Placebo
n=44 Participants
|
Aripiprazole 5 mg
n=46 Participants
|
Aripiprazole 10 mg
n=54 Participants
|
Aripiprazole 15 mg
n=48 Participants
|
|---|---|---|---|---|
|
Mean Change (Week 8 - Baseline) in the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS; Compulsion Scale Only)
|
-1.7 units on a scale
Standard Error 0.50
|
-2.6 units on a scale
Standard Error 0.50
|
-2.4 units on a scale
Standard Error 0.44
|
-3.2 units on a scale
Standard Error 0.47
|
SECONDARY outcome
Timeframe: Week 8Population: Efficacy population=all randomized participants minus 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.
Mean change (Week 8 - baseline) in the other ABC subscale scores (lethargy/social withdrawal; stereotypic behavior; hyperactivity/ noncompliance; inappropriate speech). A decrease in value indicates improvement.
Outcome measures
| Measure |
Placebo
n=49 Participants
|
Aripiprazole 5 mg
n=52 Participants
|
Aripiprazole 10 mg
n=59 Participants
|
Aripiprazole 15 mg
n=53 Participants
|
|---|---|---|---|---|
|
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores
ABC Social Withdrawal Subscale Score
|
-5.2 units on a scale
Standard Error 1.16
|
-5.8 units on a scale
Standard Error 1.15
|
-4.9 units on a scale
Standard Error 1.06
|
-7.9 units on a scale
Standard Error 1.11
|
|
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores
ABC Hyperactivity Subscale Score
|
-7.7 units on a scale
Standard Error 1.67
|
-14.0 units on a scale
Standard Error 1.64
|
-13.3 units on a scale
Standard Error 1.50
|
-16.3 units on a scale
Standard Error 1.59
|
|
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores
ABC Stereotypy Subscale Score
|
-1.8 units on a scale
Standard Error 0.69
|
-4.5 units on a scale
Standard Error 0.68
|
-4.2 units on a scale
Standard Error 0.63
|
-4.5 units on a scale
Standard Error 0.66
|
|
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores
ABC Inappropriate Speech Subscale Score
|
-1.1 units on a scale
Standard Error 0.46
|
-2.0 units on a scale
Standard Error 0.45
|
-1.8 units on a scale
Standard Error 0.41
|
-2.3 units on a scale
Standard Error 0.43
|
SECONDARY outcome
Timeframe: Week 8Population: Efficacy population=all randomized participants minus 3 patients in the placebo group (1 lost to follow-up, 1 withdrew consent, 1 no longer met study criteria), 1 participant in the 5-mg group who withdrew consent, and 1 participant in the 15-mg group who had elevated potassium levels. Data set is LOCF.
A CGI-S assessment (a 7-point scale to evaluate the severity of symptoms) was performed at baseline (1=no symptoms; 7=very severe symptoms). The patient's improvement relative to the symptoms at baseline on were assessed on a 7-point CGI-I (1=very much improved; 7=very much worse). A decrease in value indicates improvement.
Outcome measures
| Measure |
Placebo
n=41 Participants
|
Aripiprazole 5 mg
n=44 Participants
|
Aripiprazole 10 mg
n=52 Participants
|
Aripiprazole 15 mg
n=44 Participants
|
|---|---|---|---|---|
|
Mean Change (Week 8 - Baseline) in CGI-Severity (CGI-S)
|
-0.6 units on a scale
Standard Error 0.16
|
-0.9 units on a scale
Standard Error 0.15
|
-1.0 units on a scale
Standard Error 0.13
|
-1.1 units on a scale
Standard Error 0.15
|
SECONDARY outcome
Timeframe: continuously throughout the studyPopulation: Safety population=all randomized participants minus 1 patients in the placebo group (no longer met study criteria), and 1 participant in the 5-mg group who withdrew consent.
Deaths, Adverse Events (AEs), Serious AEs (SAEs), Treatment-Emergent AEs and AEs leading to discontinuation
Outcome measures
| Measure |
Placebo
n=51 Participants
|
Aripiprazole 5 mg
n=52 Participants
|
Aripiprazole 10 mg
n=59 Participants
|
Aripiprazole 15 mg
n=54 Participants
|
|---|---|---|---|---|
|
Summary of Safety
Deaths
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Summary of Safety
Treatment-emergent SAEs
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Summary of Safety
AEs leading to discontinuation of study medication
|
4 participants
|
5 participants
|
8 participants
|
4 participants
|
|
Summary of Safety
Treatment-emergent AEs overall
|
37 participants
|
46 participants
|
53 participants
|
46 participants
|
|
Summary of Safety
Treatment-emergent AEs related to study medication
|
22 participants
|
37 participants
|
50 participants
|
39 participants
|
|
Summary of Safety
Treatment-emergent extrapyramidal symptom AEs
|
6 participants
|
12 participants
|
13 participants
|
12 participants
|
SECONDARY outcome
Timeframe: Week 8Population: Safety population=all randomized participants minus 3 patients in the placebo group (1 no longer met study criteria, 2 did not have measurement at baseline and Week 8), and 1 participant in the 5-mg group who withdrew consent. Data set is LOCF.
Adjusted mean change (Week 8 - baseline) in body weight
Outcome measures
| Measure |
Placebo
n=49 Participants
|
Aripiprazole 5 mg
n=52 Participants
|
Aripiprazole 10 mg
n=59 Participants
|
Aripiprazole 15 mg
n=53 Participants
|
|---|---|---|---|---|
|
Change From Baseline in Body Weight
|
0.3 kilograms
Standard Error 0.32
|
1.3 kilograms
Standard Error 0.31
|
1.3 kilograms
Standard Error 0.29
|
1.5 kilograms
Standard Error 0.30
|
Adverse Events
Aripiprazole 10 mg
Aripiprazole 15 mg
Aripiprazole 5 mg
Placebo
Serious adverse events
| Measure |
Aripiprazole 10 mg
n=59 participants at risk
|
Aripiprazole 15 mg
n=54 participants at risk
|
Aripiprazole 5 mg
n=52 participants at risk
|
Placebo
n=51 participants at risk
|
|---|---|---|---|---|
|
Psychiatric disorders
AGGRESSION
|
1.7%
1/59
|
0.00%
0/54
|
0.00%
0/52
|
0.00%
0/51
|
|
Nervous system disorders
PRESYNCOPE
|
0.00%
0/59
|
0.00%
0/54
|
1.9%
1/52
|
0.00%
0/51
|
Other adverse events
| Measure |
Aripiprazole 10 mg
n=59 participants at risk
|
Aripiprazole 15 mg
n=54 participants at risk
|
Aripiprazole 5 mg
n=52 participants at risk
|
Placebo
n=51 participants at risk
|
|---|---|---|---|---|
|
Nervous system disorders
DROOLING
|
13.6%
8/59
|
9.3%
5/54
|
3.8%
2/52
|
0.00%
0/51
|
|
Nervous system disorders
HEADACHE
|
8.5%
5/59
|
9.3%
5/54
|
5.8%
3/52
|
3.9%
2/51
|
|
Nervous system disorders
LETHARGY
|
5.1%
3/59
|
5.6%
3/54
|
7.7%
4/52
|
0.00%
0/51
|
|
Investigations
WEIGHT INCREASED
|
1.7%
1/59
|
3.7%
2/54
|
7.7%
4/52
|
2.0%
1/51
|
|
Psychiatric disorders
INSOMNIA
|
8.5%
5/59
|
3.7%
2/54
|
1.9%
1/52
|
11.8%
6/51
|
|
Psychiatric disorders
AGGRESSION
|
3.4%
2/59
|
0.00%
0/54
|
3.8%
2/52
|
5.9%
3/51
|
|
Immune system disorders
SEASONAL ALLERGY
|
0.00%
0/59
|
1.9%
1/54
|
0.00%
0/52
|
7.8%
4/51
|
|
Nervous system disorders
TREMOR
|
11.9%
7/59
|
11.1%
6/54
|
7.7%
4/52
|
0.00%
0/51
|
|
Nervous system disorders
SEDATION
|
28.8%
17/59
|
24.1%
13/54
|
17.3%
9/52
|
5.9%
3/51
|
|
Nervous system disorders
AKATHISIA
|
3.4%
2/59
|
0.00%
0/54
|
1.9%
1/52
|
5.9%
3/51
|
|
Nervous system disorders
SOMNOLENCE
|
8.5%
5/59
|
9.3%
5/54
|
7.7%
4/52
|
3.9%
2/51
|
|
Nervous system disorders
HYPERSOMNIA
|
0.00%
0/59
|
3.7%
2/54
|
5.8%
3/52
|
0.00%
0/51
|
|
Nervous system disorders
EXTRAPYRAMIDAL DISORDER
|
6.8%
4/59
|
11.1%
6/54
|
3.8%
2/52
|
0.00%
0/51
|
|
Nervous system disorders
PSYCHOMOTOR HYPERACTIVITY
|
0.00%
0/59
|
0.00%
0/54
|
5.8%
3/52
|
3.9%
2/51
|
|
Gastrointestinal disorders
NAUSEA
|
5.1%
3/59
|
7.4%
4/54
|
1.9%
1/52
|
2.0%
1/51
|
|
Gastrointestinal disorders
VOMITING
|
20.3%
12/59
|
9.3%
5/54
|
9.6%
5/52
|
7.8%
4/51
|
|
Gastrointestinal disorders
DIARRHOEA
|
8.5%
5/59
|
9.3%
5/54
|
3.8%
2/52
|
7.8%
4/51
|
|
Gastrointestinal disorders
CONSTIPATION
|
10.2%
6/59
|
5.6%
3/54
|
3.8%
2/52
|
5.9%
3/51
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
1.7%
1/59
|
7.4%
4/54
|
3.8%
2/52
|
2.0%
1/51
|
|
Gastrointestinal disorders
SALIVARY HYPERSECRETION
|
6.8%
4/59
|
11.1%
6/54
|
1.9%
1/52
|
2.0%
1/51
|
|
Infections and infestations
NASOPHARYNGITIS
|
8.5%
5/59
|
9.3%
5/54
|
11.5%
6/52
|
3.9%
2/51
|
|
Infections and infestations
GASTROENTERITIS VIRAL
|
5.1%
3/59
|
1.9%
1/54
|
1.9%
1/52
|
0.00%
0/51
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
0.00%
0/59
|
5.6%
3/54
|
3.8%
2/52
|
0.00%
0/51
|
|
Renal and urinary disorders
ENURESIS
|
1.7%
1/59
|
5.6%
3/54
|
0.00%
0/52
|
2.0%
1/51
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
8.5%
5/59
|
5.6%
3/54
|
9.6%
5/52
|
2.0%
1/51
|
|
Metabolism and nutrition disorders
INCREASED APPETITE
|
5.1%
3/59
|
13.0%
7/54
|
19.2%
10/52
|
3.9%
2/51
|
|
Skin and subcutaneous tissue disorders
RASH
|
5.1%
3/59
|
1.9%
1/54
|
0.00%
0/52
|
2.0%
1/51
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
6.8%
4/59
|
0.00%
0/54
|
15.4%
8/52
|
3.9%
2/51
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
6.8%
4/59
|
1.9%
1/54
|
0.00%
0/52
|
0.00%
0/51
|
|
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA
|
8.5%
5/59
|
1.9%
1/54
|
3.8%
2/52
|
2.0%
1/51
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
1.7%
1/59
|
7.4%
4/54
|
1.9%
1/52
|
2.0%
1/51
|
|
Respiratory, thoracic and mediastinal disorders
PHARYNGOLARYNGEAL PAIN
|
1.7%
1/59
|
1.9%
1/54
|
1.9%
1/52
|
5.9%
3/51
|
|
General disorders
THIRST
|
1.7%
1/59
|
1.9%
1/54
|
5.8%
3/52
|
2.0%
1/51
|
|
General disorders
FATIGUE
|
22.0%
13/59
|
18.5%
10/54
|
3.8%
2/52
|
0.00%
0/51
|
|
General disorders
PYREXIA
|
11.9%
7/59
|
9.3%
5/54
|
5.8%
3/52
|
0.00%
0/51
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER