Trial Outcomes & Findings for Brexpiprazole in Treatment of Children and Adolescents With Irritability Associated With Autism Spectrum Disorder (NCT NCT04174365)

Last Updated: 2025-08-28

Results Overview

The ABC is a parent-reported rating scale designed to assess treatment effects on problem behavior in participants with intellectual disabilities. The ABC scale has 58 items, which divide into 5 subscales as follows: (1) Irritability, Agitation; (2) Lethargy, Social Withdrawal; (3) Stereotypic Behavior; (4) Hyperactivity, Noncompliance; and (5) Inappropriate Speech. Each of the 58 ABC items is rated on a 4-point scale (0=not at all a problem; 1=the behavior is a problem, but slight in degree;2=the problem is moderately serious; 3=the problem is severe in degree). ABC-I measures emotional and behavioral symptoms of ASD, including aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. ABC-I total score is the sum of the ratings over 15 ABC items. Individual scores were summed, thus the ABC-I total score ranges from 0 to 45. Higher scores represent the worst condition. A negative change from baseline indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

119 participants

Primary outcome timeframe

Baseline to Week 8

Results posted on

2025-08-28

Participant Flow

Participants took part in the study at 40 sites in the United States from 30 October 2019 to 9 September 2022.

A total of 260 participants were screened, of which 119 participants were randomized to receive brexpiprazole or placebo.

Participant milestones

Participant milestones
Measure	Brexpiprazole Participants received flexible doses of brexpiprazole 0.25 to 3 milligram per day (mg/day), orally, once daily (QD) up to Week 8. For participants with body weight \< 50 kilograms (kg) the dose was titrated up from 0.25 mg/day on Days 1 to 3, followed by 0.5 mg on Days 4 to 7, and to 1 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 1.5 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8. For participants with body weight ≥ 50 kg the dose was titrated up from 0.5 mg/day on Days 1 to 3, followed by 1.5 mg on Days 4 to 7, and to 2 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 3 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8.	Placebo Participants received brexpiprazole matching placebo orally, QD, in the same way as brexpiprazole up to Week 8.
Overall Study STARTED	60	59
Overall Study Randomized Sample	60	59
Overall Study Safety Sample	58	57
Overall Study Efficacy Sample	58	56
Overall Study COMPLETED	52	52
Overall Study NOT COMPLETED	8	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Brexpiprazole Participants received flexible doses of brexpiprazole 0.25 to 3 milligram per day (mg/day), orally, once daily (QD) up to Week 8. For participants with body weight \< 50 kilograms (kg) the dose was titrated up from 0.25 mg/day on Days 1 to 3, followed by 0.5 mg on Days 4 to 7, and to 1 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 1.5 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8. For participants with body weight ≥ 50 kg the dose was titrated up from 0.5 mg/day on Days 1 to 3, followed by 1.5 mg on Days 4 to 7, and to 2 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 3 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8.	Placebo Participants received brexpiprazole matching placebo orally, QD, in the same way as brexpiprazole up to Week 8.
Overall Study Lost to Follow-up	1	2
Overall Study Adverse Event	2	1
Overall Study Subject Withdrew Consent To Participate	1	0
Overall Study Subject Was Withdrawn From Participation By Parent/Guardian	2	1
Overall Study Protocol Deviation	1	0
Overall Study Lack of Efficacy	0	2
Overall Study Disease Relapse	1	0
Overall Study Reason Not Specified	0	1

Baseline Characteristics

Randomized Sample included all participants who were randomized into the trial. 'Number analyzed' indicates the number of participants with data available for analysis at Baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brexpiprazole n=60 Participants Participants received flexible doses of brexpiprazole 0.25 to 3 mg/day, orally, QD up to Week 8. For participants with body weight \< 50 kg the dose was titrated up from 0.25 mg/day on Days 1 to 3, followed by 0.5 mg on Days 4 to 7, and to 1 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 1.5 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8. For participants with body weight ≥ 50 kg the dose was titrated up from 0.5 mg/day on Days 1 to 3, followed by 1.5 mg on Days 4 to 7, and to 2 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 3 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8.	Placebo n=59 Participants Participants received brexpiprazole matching placebo orally, QD, in the same way as brexpiprazole up to Week 8.	Total n=119 Participants Total of all reporting groups
Age, Continuous	9.8 years STANDARD_DEVIATION 2.9 • n=60 Participants	10.0 years STANDARD_DEVIATION 3.2 • n=59 Participants	9.9 years STANDARD_DEVIATION 3.0 • n=119 Participants
Sex: Female, Male Female	6 Participants n=60 Participants	9 Participants n=59 Participants	15 Participants n=119 Participants
Sex: Female, Male Male	54 Participants n=60 Participants	50 Participants n=59 Participants	104 Participants n=119 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=60 Participants	7 Participants n=59 Participants	15 Participants n=119 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	52 Participants n=60 Participants	52 Participants n=59 Participants	104 Participants n=119 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=60 Participants	0 Participants n=59 Participants	0 Participants n=119 Participants
Race/Ethnicity, Customized Race · White	49 Participants n=60 Participants	45 Participants n=59 Participants	94 Participants n=119 Participants
Race/Ethnicity, Customized Race · Black or African American	3 Participants n=60 Participants	10 Participants n=59 Participants	13 Participants n=119 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=60 Participants	0 Participants n=59 Participants	0 Participants n=119 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=60 Participants	3 Participants n=59 Participants	5 Participants n=119 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	1 Participants n=60 Participants	0 Participants n=59 Participants	1 Participants n=119 Participants
Race/Ethnicity, Customized Race · Other	5 Participants n=60 Participants	1 Participants n=59 Participants	6 Participants n=119 Participants
Region of Enrollment United States	60 participants n=60 Participants	59 participants n=59 Participants	119 participants n=119 Participants
Aberrant Behavior Checklist - Irritability (ABC-I) Subscale Score	29.7 score on a scale STANDARD_DEVIATION 8.0 • n=60 Participants • Randomized Sample included all participants who were randomized into the trial. 'Number analyzed' indicates the number of participants with data available for analysis at Baseline.	28.6 score on a scale STANDARD_DEVIATION 7.6 • n=58 Participants • Randomized Sample included all participants who were randomized into the trial. 'Number analyzed' indicates the number of participants with data available for analysis at Baseline.	29.1 score on a scale STANDARD_DEVIATION 7.8 • n=118 Participants • Randomized Sample included all participants who were randomized into the trial. 'Number analyzed' indicates the number of participants with data available for analysis at Baseline.
Clinical Global Impression - Severity (CGI-S) Score	4.9 score on a scale STANDARD_DEVIATION 0.7 • n=60 Participants • Randomized Sample included all participants who were randomized into the trial.	4.7 score on a scale STANDARD_DEVIATION 0.5 • n=59 Participants • Randomized Sample included all participants who were randomized into the trial.	4.8 score on a scale STANDARD_DEVIATION 0.7 • n=119 Participants • Randomized Sample included all participants who were randomized into the trial.

PRIMARY outcome

Timeframe: Baseline to Week 8

Population: Efficacy sample included all randomized participants who took at least 1 dose of brexpiprazole or placebo and had baseline and at least 1 post-baseline assessment of the primary efficacy variable ABC-I subscale score during the double-blind treatment phase. 'Overall number of participants analyzed' indicates the number of participants with data available for analysis at the specified time point.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=48 Participants Participants received flexible doses of brexpiprazole 0.25 to 3 mg/day, orally, QD up to Week 8. For participants with body weight \< 50 kg the dose was titrated up from 0.25 mg/day on Days 1 to 3, followed by 0.5 mg on Days 4 to 7, and to 1 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 1.5 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8. For participants with body weight ≥ 50 kg the dose was titrated up from 0.5 mg/day on Days 1 to 3, followed by 1.5 mg on Days 4 to 7, and to 2 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 3 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8.	Placebo n=46 Participants Participants received brexpiprazole matching placebo orally, QD, in the same way as brexpiprazole up to Week 8.
Mean Change From Baseline to Week 8 in Aberrant Behavior Checklist - Irritability (ABC-I) Subscale Score	-10.1 score on a scale Standard Error 1.28	-8.87 score on a scale Standard Error 1.25

SECONDARY outcome

Timeframe: Baseline to Week 8

The CGI-S scale is a clinician-rated assessment that evaluates the severity of a participant's condition with a focus on symptoms of irritability on a 7-point scale. The investigator (or rater) answered the following question: "Considering your total clinical experience with this particular population, how ill was the participant at this time with regard to symptoms of irritability?" Response choices were 0 = not assessed; 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients. Higher scores indicate more severe illness. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=50 Participants Participants received flexible doses of brexpiprazole 0.25 to 3 mg/day, orally, QD up to Week 8. For participants with body weight \< 50 kg the dose was titrated up from 0.25 mg/day on Days 1 to 3, followed by 0.5 mg on Days 4 to 7, and to 1 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 1.5 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8. For participants with body weight ≥ 50 kg the dose was titrated up from 0.5 mg/day on Days 1 to 3, followed by 1.5 mg on Days 4 to 7, and to 2 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 3 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8.	Placebo n=46 Participants Participants received brexpiprazole matching placebo orally, QD, in the same way as brexpiprazole up to Week 8.
Mean Change From Baseline to Week 8 in Clinical Global Impression - Severity (CGI-S) Score	-1.16 score on a scale Standard Error 0.15	-1.09 score on a scale Standard Error 0.15

Adverse Events

Brexpiprazole

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Brexpiprazole n=58 participants at risk Participants received flexible doses of brexpiprazole 0.25 to 3 mg/day, orally, QD up to Week 8. For participants with body weight \< 50 kg the dose was titrated up from 0.25 mg/day on Days 1 to 3, followed by 0.5 mg on Days 4 to 7, and to 1 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 1.5 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8. For participants with body weight ≥ 50 kg the dose was titrated up from 0.5 mg/day on Days 1 to 3, followed by 1.5 mg on Days 4 to 7, and to 2 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 3 mg/day after Day 15. The dose was fixed after Week 6 and administration continued for another 2 weeks until Week 8.	Placebo n=57 participants at risk Participants received brexpiprazole matching placebo orally, QD, in the same way as brexpiprazole up to Week 8.
Gastrointestinal disorders Vomiting	5.2% 3/58 • From first dose through 21 days after last dose of study drug (up to Week 11) Safety sample included all enrolled participants who received at least 1 dose of brexpiprazole or placebo.	1.8% 1/57 • From first dose through 21 days after last dose of study drug (up to Week 11) Safety sample included all enrolled participants who received at least 1 dose of brexpiprazole or placebo.
Nervous system disorders Headache	10.3% 6/58 • From first dose through 21 days after last dose of study drug (up to Week 11) Safety sample included all enrolled participants who received at least 1 dose of brexpiprazole or placebo.	1.8% 1/57 • From first dose through 21 days after last dose of study drug (up to Week 11) Safety sample included all enrolled participants who received at least 1 dose of brexpiprazole or placebo.
Nervous system disorders Somnolence	12.1% 7/58 • From first dose through 21 days after last dose of study drug (up to Week 11) Safety sample included all enrolled participants who received at least 1 dose of brexpiprazole or placebo.	5.3% 3/57 • From first dose through 21 days after last dose of study drug (up to Week 11) Safety sample included all enrolled participants who received at least 1 dose of brexpiprazole or placebo.

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: 1-609-524-6788

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
Publication restrictions are in place

Restriction type: OTHER