Brexpiprazole in Treatment of Children and Adolescents With Irritability Associated With Autism Spectrum Disorder (Anchor)

A Phase 3, Multicenter, Randomized, Double-blind, Placebo Controlled Trial of Brexpiprazole in Treatment of Children and Adolescents With Irritability Associated With Autism Spectrum Disorder

The purpose of this study is to find out about the potential benefits and safety of brexpiprazole in children and adolescent participants, aged 5 to 17, with irritability associated with autism spectrum disorder.

Study Overview

• Status: Completed
• Conditions: Irritability Associated With Autism Spectrum Disorder (ASD)
• Intervention / Treatment: Drug: Brexpiprazole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • For additional information regarding sites

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Primary Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ASD
• Aberrant Behavior checklist - Irritability (ABC-I) subscale score of ≥ 18
• Clinical Global Impressions - Severity (CGI-S) scale score pertaining to irritability ≥ 4
• Mental age of ≥ 2 years as determined by Investigator based upon school participation, social history or medical records
• Ability for parent/caregiver to follow all protocol procedures
• Able to swallow tablets
• Able to discontinue all prohibited concomitant medications to meet protocol required washouts prior to and during the trial period

Key Exclusion Criteria:

• Primary diagnosis of bipolar I disorder, including any DSM-5 current diagnosis of bipolar II disorder, schizophrenia, schizoaffective disorder, major depressive episode, and post-traumatic stress disorder (PTSD). Attention-deficit/hyperactivity disorder (ADHD) maybe exclusionary if it is the primary disorder, or is not stable or adequately treated.
• current or historical diagnosis of Fragile-X Syndrome or Rett's Disorder
• history of neuroleptic malignant syndrome
• a significant risk of committing violent acts, serious self-harm, or suicide
• epilepsy, a history of seizures, or a history of severe head trauma or stroke, or have a history or current evidence of other unstable medical conditions
• current hypothyroidism or hyperthyroidism
• uncontrolled Type I or Type II diabetes
• uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension
• Weight < 15 kg
• Previous exposure to brexpiprazole
• Sexually active males or females, who could become pregnant, not agreeing to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days at the end of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Brexpiprazole; Oral tablet; take once daily; Other Names: brexpiprazole, OPC-34712 and LuAF41156
Placebo Comparator: Placebo; Participants received brexpiprazole matching placebo orally, QD, in the same way as brexpiprazole up to Week 8.	Drug: Placebo; Administered orally daily for up to Week 8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to Week 8 in Aberrant Behavior Checklist - Irritability (ABC-I) Subscale Score	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.	Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to Week 8 in Clinical Global Impression - Severity (CGI-S) Score	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.	Baseline to Week 8

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2019
• Primary Completion (Actual): August 8, 2022
• Study Completion (Actual): September 9, 2022

Study Registration Dates

• First Submitted: November 20, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Estimated): August 28, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: ASD; Autism; Autism Spectrum Disorder; Irritability
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; brexpiprazole
• Other Study ID Numbers: 331-201-00148

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No