Trial Outcomes & Findings for Study of Aripiprazole in the Treatment of Children and Adolescents With Autistic Disorder (AD) (NCT NCT00332241)

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

98 participants

Primary outcome timeframe

Week 8

Results posted on

2013-12-02

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo oral placebo once daily (QD)	Aripiprazole oral aripiprazole 2 to 15 mg QD
Overall Study STARTED	51	47
Overall Study COMPLETED	36	39
Overall Study NOT COMPLETED	15	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo oral placebo once daily (QD)	Aripiprazole oral aripiprazole 2 to 15 mg QD
Overall Study Lack of Efficacy	6	1
Overall Study Adverse Event	3	5
Overall Study Withdrawal by Subject	2	1
Overall Study Lost to Follow-up	4	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=51 Participants oral placebo once daily (QD)	Aripiprazole n=47 Participants oral aripiprazole 2 to 15 mg QD	Total n=98 Participants Total of all reporting groups
Age, Customized 6 to 12 years	46 participants n=5 Participants	37 participants n=7 Participants	83 participants n=5 Participants
Age, Customized 13 to 17 years	5 participants n=5 Participants	10 participants n=7 Participants	15 participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	42 Participants n=7 Participants	86 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	7 participants n=5 Participants	11 participants n=7 Participants	18 participants n=5 Participants
Race/Ethnicity, Customized White	41 participants n=5 Participants	32 participants n=7 Participants	73 participants n=5 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	8 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic/Latino	43 participants n=5 Participants	41 participants n=7 Participants	84 participants n=5 Participants
Weight Group <40 kilograms	32 Participants n=5 Participants	26 Participants n=7 Participants	58 Participants n=5 Participants
Weight Group ≥40 kilograms	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
Body Mass Index	19.96 kg/cm2 STANDARD_DEVIATION 5.392 • n=5 Participants	21.08 kg/cm2 STANDARD_DEVIATION 5.394 • n=7 Participants	20.50 kg/cm2 STANDARD_DEVIATION 5.395 • n=5 Participants
Height	138.6 centimeters STANDARD_DEVIATION 14.7 • n=5 Participants	140.9 centimeters STANDARD_DEVIATION 18.80 • n=7 Participants	139.7 centimeters STANDARD_DEVIATION 16.74 • n=5 Participants
Weight	40.6 kilograms STANDARD_DEVIATION 18.92 • n=5 Participants	43.9 kilograms STANDARD_DEVIATION 19.15 • n=7 Participants	42.2 kilograms STANDARD_DEVIATION 19.01 • n=5 Participants

PRIMARY outcome

Timeframe: Week 8

Population: Efficacy population=all randomized participants minus 2 patients in the placebo group (1 lost to follow-up, 1 withdrew consent) and 1 participant in the aripiprazole group who discontinued due to AE on Day 2. Data set is LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants oral placebo once daily (QD)	Aripiprazole n=46 Participants oral aripiprazole 2 to 15 mg QD
Mean Change (Week 8 - Baseline) in the Autistic Behavior Checklist (ABC) Irritability Subscale Score	-5.0 units on a scale Standard Error 1.43	-12.9 units on a scale Standard Error 1.44

SECONDARY outcome

Timeframe: Week 8

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

Outcome measures
Measure	Placebo n=49 Participants oral placebo once daily (QD)	Aripiprazole n=46 Participants oral aripiprazole 2 to 15 mg QD
Mean Clinical Global Impressions Improvement Scale (CGI-I) Score	3.6 units on a scale Standard Error 0.18	2.2 units on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Week 8

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

Outcome measures
Measure	Placebo n=49 Participants oral placebo once daily (QD)	Aripiprazole n=46 Participants oral aripiprazole 2 to 15 mg QD
Number of Participants With Response at Week 8	7 participant	24 participant

SECONDARY outcome

Timeframe: Week 8

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 decrease in value indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants oral placebo once daily (QD)	Aripiprazole n=43 Participants oral aripiprazole 2 to 15 mg QD
Mean Change (Week 8 - Baseline) in the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS; Compulsion Scale Only)	-0.8 units on a scale Standard Error 0.52	-3.8 units on a scale Standard Error 0.50

SECONDARY outcome

Timeframe: Week 8

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

Outcome measures
Measure	Placebo n=49 Participants oral placebo once daily (QD)	Aripiprazole n=46 Participants oral aripiprazole 2 to 15 mg QD
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores ABC Hyperactivity Subscale Score	-2.8 units of a scale Standard Error 1.5	-12.7 units of a scale Standard Error 1.52
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores ABC Stereotypy Subscale Score	-2.0 units of a scale Standard Error 0.62	-4.8 units of a scale Standard Error 0.63
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores ABC Inappropriate Speech Subscale Score	-0.4 units of a scale Standard Error 0.39	-2.5 units of a scale Standard Error 0.39
Mean Change (Week 8 - Baseline) in the Other ABC Subscale Scores ABC Social Withdrawal Subscale Score	-6.2 units of a scale Standard Error 1.13	-7.9 units of a scale Standard Error 1.15

SECONDARY outcome

Timeframe: Week 8

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

Outcome measures
Measure	Placebo n=40 Participants oral placebo once daily (QD)	Aripiprazole n=40 Participants oral aripiprazole 2 to 15 mg QD
Mean Change (Week 8 - Baseline) in CGI-Severity (CGI-S)	-0.4 units on a scale Standard Deviation 0.15	-1.2 units on a scale Standard Deviation 0.14

SECONDARY outcome

Timeframe: continuous throughout the study

Population: Safety population=all randomized participants minus 1 patient in the placebo group lost to follow-up. Data set is LOCF.

Deaths, Adverse Events (AEs), Serious AEs (SAEs), Treatment-Emergent AEs and AEs leading to discontinuation

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants oral placebo once daily (QD)	Aripiprazole n=47 Participants oral aripiprazole 2 to 15 mg QD
Summary of Safety Deaths	0 participants	0 participants
Summary of Safety Treatment-emergent SAEs	0 participants	0 participants
Summary of Safety AEs leading to discontinuation	3 participants	5 participants
Summary of Safety Treatment-emergent AEs overall	36 participants	43 participants
Summary of Safety Treatment-emergent AEs realted to study drug	25 participants	39 participants
Summary of Safety Treatment-emergent extrapyramidal symptom AEs	4 participants	7 participants

SECONDARY outcome

Timeframe: Week 8

Population: Safety population=all randomized participants minus 1 patient in the placebo group lost to follow-up. Includes all participants with weight measurement at baseline and timepoint. Data set is LOCF.

Adjusted mean change (Week 8 - baseline) in body weight

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants oral placebo once daily (QD)	Aripiprazole n=45 Participants oral aripiprazole 2 to 15 mg QD
Change From Baseline in Body Weight	0.8 kilograms Standard Error 0.29	2.0 kilograms Standard Error 0.30

Adverse Events

Aripiprazole

Serious events: 0 serious events

Other events: 38 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Aripiprazole n=47 participants at risk	Placebo n=50 participants at risk
Psychiatric disorders INSOMNIA	6.4% 3/47	8.0% 4/50
Psychiatric disorders AGGRESSION	2.1% 1/47	8.0% 4/50
Nervous system disorders TREMOR	8.5% 4/47	0.00% 0/50
Nervous system disorders DROOLING	8.5% 4/47	0.00% 0/50
Nervous system disorders HEADACHE	6.4% 3/47	16.0% 8/50
Nervous system disorders SEDATION	10.6% 5/47	2.0% 1/50
Nervous system disorders SOMNOLENCE	17.0% 8/47	4.0% 2/50
Gastrointestinal disorders VOMITING	14.9% 7/47	4.0% 2/50
Gastrointestinal disorders DIARRHOEA	8.5% 4/47	10.0% 5/50
Infections and infestations NASOPHARYNGITIS	4.3% 2/47	6.0% 3/50
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	2.1% 1/47	10.0% 5/50
Renal and urinary disorders ENURESIS	6.4% 3/47	8.0% 4/50
Metabolism and nutrition disorders INCREASED APPETITE	14.9% 7/47	10.0% 5/50
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	6.4% 3/47	2.0% 1/50
General disorders FATIGUE	21.3% 10/47	4.0% 2/50
General disorders PYREXIA	8.5% 4/47	2.0% 1/50

Additional Information

BMS Study Director

Bristol-Myers Squibb

Email: [email protected]

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