Brexpiprazole in Treatment of Children and Adolescents With Irritability Associated With Autism Spectrum Disorder for Subjects That Have Completed Participation in 331-201-00148

NCT04258839 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 331-201-001912018-004899-35
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 28

Brief Summary

The purpose of this study is to evaluate the long-term safety and tolerability of brexpiprazole in children and adolescent participants, aged 5 to 17, with irritability associated with autism spectrum disorder.

Conditions

Irritability Associated With Autism Spectrum Disorder

Keywords

Autism; Autism Spectrum Disorder; ASD; Irritability

Outcome Measures

Primary Outcomes (18)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs

  An AE is any untoward medical occurrence in a clinical trial participant administered a medicinal product that does not necessarily have a causal relationship with the treatment. An SAE: AE that results in the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions i.e. fatal, life-threatening, result in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, and requires inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE that started after trial drug treatment; or if the event was continuous from baseline and was worsening, serious, trial drug-related, or resulted in death, discontinuation, interruption, or reduction of trial therapy. TEAEs were graded as, Mild: Discomfort noticed, but no disruption to daily activity, Moderate: Discomfort sufficient to reduce or affect normal daily activity, and Severe: Inability to work or perform normal daily activity.

  From the first dose of study drug (in current study) up to 21 days after the last dose of study drug (up to approximately 29 weeks)

• Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs

  Vital signs measurements included body weight, body temperature, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate. Blood pressure (i.e., SBP, DBP) and heart rate were measured in the supine and standing positions after the participant had been in each position for at least 3 minutes. The participants were categorized based on the clinically relevant vital sign values as per protocol-predefined criteria. The categories with at least one participant with clinically significant value outside the normal range for vital signs are reported.

  Baseline (current study) up to Week 26

• Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities

  Twelve-lead ECG recordings were obtained after the participant was supine and at rest for at least 5 minutes. Criteria for identifying ECG measurements of potential clinical relevance included Rate: Tachycardia (Vent ≥110 beats per minute \[bpm\]; increase ≥15bpm), Bradycardia (Vent ≤ 60bpm; decrease ≥15bpm); Rhythm: Sinus tachycardia (≥ 110bpm; an increase of ≥15 bpm), Sinus bradycardia (≤ 60bpm; a decrease of ≥15 bpm), Supraventricular premature beat (not present at baseline and present post-baseline), Conduction: Right bundle branch block (not present at baseline and present post-baseline) and ST/T Morphology: Symmetrical T-Wave Inversion (not present at baseline and present post-baseline). The categories with at least one participant with clinically relevant ECG abnormalities are reported.

  Baseline (current study) up to Week 26

• Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities

  Laboratory assessments included - serum chemistry including prolactin and thyrotropin, hematology, and urinalysis. Number of participants with potentially clinically relevant laboratory test abnormalities were reported as per criteria defined in SAP. The categories with at least one participant with clinically relevant value outside the normal range for laboratory assessments are reported.

  Baseline (current study) up to Week 26

• Number of Participants With Potentially Clinically Relevant Abnormal Physical Examination Values

  Physical examination included measurement of height and the examination of the head, ears, eyes, nose, and throat (HEENT); thorax; abdomen; urogenital; extremities; neurological; and skin and mucosae. Participants with abnormal values, as assessed by the investigator were reported.

  Baseline (current study) up to Week 26

• Number of Participants With Suicidality as Measured by Columbia-Suicide Severity Rating Scale (C-SSRS)

  Suicidality as defined as at least one occurrence of suicidal ideation or suicidal behavior, was assessed using C-SSRS. The assessment included "yes" or "no" responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) \& suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings were provided for suicidal ideation: Score range of 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent), higher total scores indicate more suicidal ideation; Suicidal behavior: Score range of 0 (no suicidal behavior) to 4 (actual suicide attempt), higher total scores indicate more suicidal behavior. Number of participants with at least one occurrence of suicidal ideation or suicidal behavior was reported.

  Baseline (current study) up to Week 26

• Change From Baseline in Simpson Angus Scale (SAS) Total Score at Week 2

  SAS was used to evaluate extrapyramidal symptoms (EPS). The SAS consists of a list of 10 symptoms of Parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Severity of each item was rated on a 5-point Likert scale, with a score of 0 (absence of symptoms) to 4 (severe condition). The SAS total score is the sum of the scores of all 10 items, ranging from 0 to 40 where a higher score indicates a severe condition. Negative change from baseline indicates absence of symptoms.

  Baseline and Week 2

• Change From Baseline in SAS Total Score at Week 14

  SAS was used to evaluate extrapyramidal symptoms (EPS). The SAS consists of a list of 10 symptoms of Parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Severity of each item was rated on a 5-point Likert scale, with a score of 0 (absence of symptoms) to 4 (severe condition). The SAS total score is the sum of the scores of all 10 items, ranging from 0 to 40 where a higher score indicates a severe condition. Negative change from baseline indicates absence of symptoms.

  Baseline and Week 14

• Change From Baseline in SAS Total Score at Week 26

  SAS was used to evaluate extrapyramidal symptoms (EPS). The SAS consists of a list of 10 symptoms of Parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Severity of each item was rated on a 5-point Likert scale, with a score of 0 (absence of symptoms) to 4 (severe condition). The SAS total score is the sum of the scores of all 10 items, ranging from 0 to 40 where a higher score indicates a severe condition. Negative change from baseline indicates absence of symptoms.

  Baseline and Week 26

• Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Week 2

  The AIMS is a 12-item scale. The first 10 items are rated on a Likert 5-point scale from 0 to 4 (0 = best, 4 = worst). An item score of 0, depending on specific item, means either "no abnormal Involuntary movement (AIM)" or "no incapacitation due to AIM" or "no awareness of AIM". An item score of 4 means either "severe AIM" or "severe incapacitation due to AIM" or "being aware of, and severe distress caused by AIM". Items 11 and 12 are related to dental status, taking dichotomous response: 0 = no and 1 = yes. AIMS movement score is the sum of the ratings for the first seven items with possible total scores of 0 to 28, where a higher score indicates a severe condition.

  Baseline and Week 2

• Change From Baseline in AIMS Total Score at Week 14

  The AIMS is a 12-item scale. The first 10 items are rated on a Likert 5-point scale from 0 to 4 (0 = best, 4 = worst). An item score of 0, depending on specific item, means either "no abnormal Involuntary movement (AIM)" or "no incapacitation due to AIM" or "no awareness of AIM". An item score of 4 means either "severe AIM" or "severe incapacitation due to AIM" or "being aware of, and severe distress caused by AIM". Items 11 and 12 are related to dental status, taking dichotomous response: 0 = no and 1 = yes. AIMS movement score is the sum of the ratings for the first seven items with possible total scores of 0 to 28, where a higher score indicates a severe condition.

  Baseline and Week 14

• Change From Baseline in AIMS Total Score at Week 26

  The AIMS is a 12-item scale. The first 10 items are rated on a Likert 5-point scale from 0 to 4 (0 = best, 4 = worst). An item score of 0, depending on specific item, means either "no abnormal Involuntary movement (AIM)" or "no incapacitation due to AIM" or "no awareness of AIM". An item score of 4 means either "severe AIM" or "severe incapacitation due to AIM" or "being aware of, and severe distress caused by AIM". Items 11 and 12 are related to dental status, taking dichotomous response: 0 = no and 1 = yes. AIMS movement score is the sum of the ratings for the first seven items with possible total scores of 0 to 28, where a higher score indicates a severe condition. A negative change from baseline indicates less symptoms.

  Baseline and Week 26

• Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score at Week 2

  The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the participant, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items were rated on a 4-point Likert scale, with a score of 0 (absence of symptoms) to 3 (severe condition) and the global clinical assessment was rated on a 6-point scale, with a score of 0 (absence of symptoms) to 5 (severe akathisia). Total score is the sum of the scores of all 4 items, ranging from 0 to 14. Lower scores indicate less symptoms.

  Baseline and Week 2

• Change From Baseline in BARS Score at Week 14

  The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the participant, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items were rated on a 4-point Likert scale, with a score of 0 (absence of symptoms) to 3 (severe condition) and the global clinical assessment was rated on a 6-point scale, with a score of 0 (absence of symptoms) to 5 (severe akathisia). Total score is the sum of the scores of all 4 items, ranging from 0 to 14. Lower scores indicate less symptoms and negative change from baseline indicate less symptoms.

  Baseline and Week 14

• Change From Baseline in BARS Score at Week 26

  The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the participant, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items were rated on a 4-point Likert scale, with a score of 0 (absence of symptoms) to 3 (severe condition) and the global clinical assessment was rated on a 6-point scale, with a score of 0 (absence of symptoms) to 5 (severe akathisia). Total score is the sum of the scores of all 4 items, ranging from 0 to 14. Lower scores indicate less symptoms and negative change from baseline indicate less symptoms.

  Baseline and Week 26

• Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 14

  Percentage of participants who had significant weight gain (≥ 7% increase in body weight relative to baseline) and significant weight loss (≥ 7% decrease in body weight relative to baseline) were reported.

  Baseline up to Week 14

• Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 26

  Percentage of participants who had significant weight gain (≥ 7% increase in body weight relative to baseline) and significant weight loss (≥ 7% decrease in body weight relative to baseline) were reported.

  Baseline up to Week 26

• Time to Discontinuation Due to AE

  The time to discontinuation due to AE was defined as the total number of days between the enrolment date and the discontinuation date. The time to discontinuation was analyzed using the Kaplan Meier curve.

  Baseline (in current study) up to 21 days post last dose of study drug (up to approximately 29 weeks)

Secondary Outcomes (2)

• Mean Change From Baseline to Week 26 in Aberrant Behavior Checklist - Irritability (ABC-I) Subscale Score

  Baseline (current study), Week 26

• Mean Change From Baseline to Week 26 in Clinical Global Impression - Severity (CGI-S) Scale Score

  Baseline (current study), Week 26

Study Arms (1)

Brexpiprazole

EXPERIMENTAL

Participants received brexpiprazole based on the body weight for 26 weeks in this study. Participants with body weight \< 50 kilograms (kg), received brexpiprazole tablets orally, once daily (QD) at dose of 0.25 mg on Days 1 to 3 followed by 0.5 mg on Days 4 to 7 and 1 mg on Days 8 to 14. Based on the investigator's judgment, the dose was increased to 1 or 1.5 mg starting from Day 15 until week 26. Participants with body weight ≥ 50 kg received brexpiprazole tablet orally, QD at dose of 0.5 mg on Days 1 to 3, followed by 1.5 mg on Days 4 to 7, and 2 mg on Days 8 to 14. Based on the investigator's judgment the dose was increased to 1.5, 2, or 3 mg starting from Day 15 until week 26.

Drug: Brexpiprazole

Interventions

Brexpiprazole DRUG

Oral tablet; taken once daily

Also known as: OPC-34712, LuAF41156

Brexpiprazole

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• to 17 year of age or turned 18 while enrolled in the 331-201-00148 study
• Autism Spectrum Disorder
• Completion of 331-201-00148 trial
• Investigator assessment

You may not qualify if:

• Did not complete treatment period or incurred significant protocol deviations during 331-201-00148 study
• Sexually active males or female of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose
• Female with positive pregnancy test

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• H. Lundbeck A/S: collaborator

Study Sites (28)

Dothan Behavioral Medicine Clinic

Dothan, Alabama, 36303, United States

Location

Southwest Autism Research and Resource Center

Phoenix, Arizona, 85006, United States

Location

University of California San Francisco, Nancy Friend Pritzker Psychiatry

San Francisco, California, 94143-3132, United States

Location

APG Research

Orlando, Florida, 32803, United States

Location

Autism Assessment, Research, Treatment and Services (AARTS) center

Chicago, Illinois, 60612, United States

Location

Research site

Lake Charles, Louisiana, 70629, United States

Location

The Lurie Center for Autism

Lexington, Massachusetts, 02421-3114, United States

Location

Research site

Bloomfield Hills, Michigan, 48302, United States

Location

Thompson Center for Autism and Neurodevelopment

Columbia, Missouri, 65211, United States

Location

Research site

Saint Charles, Missouri, 63304, United States

Location

Alivation

Lincoln, Nebraska, 68526, United States

Location

Center for Psychiatry and Behavioral Medicine Inc.

Las Vegas, Nevada, 89128, United States

Location

Rutger's-New Jersey Medical Scholl Clinical Research Unit

Newark, New Jersey, 07103, United States

Location

For additional information regarding sites

Princeton, New Jersey, 08540, United States

Location

Bioscience Research

Mount Kisco, New York, 10549, United States

Location

Research site

New York, New York, 10036, United States

Location

Finger Lakes Clinical Research

Rochester, New York, 14618, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10314, United States

Location

Research Site

Avon Lake, Ohio, 44012, United States

Location

The Holloway Group, Inc

Oklahoma City, Oklahoma, 73116, United States

Location

Access Clinical Trials

Nashville, Tennessee, 37203, United States

Location

Research site

Austin, Texas, 78759, United States

Location

Cedar Health Research

Dallas, Texas, 75251, United States

Location

Research site

San Antonio, Texas, 78249, United States

Location

UT Health San Antonio Long School of Medicine, Department of Psychiatry and Behavioral Sciences

San Antonio, Texas, 78289, United States

Location

Family Psychiatry of the Woodlands

The Woodlands, Texas, 77381, United States

Location

Woodstock Research Center

Woodstock, Vermont, 05091, United States

Location

Core Clinical Research

Everett, Washington, 98201, United States

Location

MeSH Terms

Conditions

Autistic Disorder; Autism Spectrum Disorder

Interventions

brexpiprazole

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

clinicaltransparency@otsuka-us.com

1-609-524-6788

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: February 6, 2020
• Study Start: January 23, 2020
• Primary Completion: March 16, 2023
• Study Completion: March 16, 2023
• Last Updated: May 30, 2024
• Results First Posted: May 30, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com

Locations

US (28)