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

Phase 3

Completed

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received brexpiprazole matching placebo orally, QD, in the same way as brexpiprazole up to Week 8.
Brexpiprazole	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.

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline to Week 8 in Aberrant Behavior Checklist - Irritability (ABC-I) Subscale Score	Baseline to Week 8	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.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline to Week 8 in Clinical Global Impression - Severity (CGI-S) Score	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.

Locations (1): For additional information regarding sites
🇺🇸
Princeton, New Jersey, United States
For additional information regarding sites
🇺🇸Princeton, New Jersey, United States