Irritability Associated With Autism Spectrum DisorderPhase 3NCT04258839
Brexpiprazole in Treatment of Children and Adolescents With Irritability Associated With Autism Spectrum Disorder for Subjects That Have Completed Participation in 331-201-00148
A Phase 3 study testing Brexpiprazole in people with Irritability Associated With Autism Spectrum Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 28 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Irritability Associated With Autism Spectrum Disorder
- What is being tested?
- Brexpiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 28 sitesUnited States
- Study dates
- 23 Jan 2020to 16 Mar 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 5 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
Who cannot join
- 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
Trial locations and contacts
28 sites in 1 country.
28 sites in 1 country
United States28 sites
Research site
Austin, Texas, 78759
Research Site
Avon Lake, Ohio, 44012
Research site
Bloomfield Hills, Michigan, 48302
Autism Assessment, Research, Treatment and Services (AARTS) center
Chicago, Illinois, 60612
Thompson Center for Autism and Neurodevelopment
Columbia, Missouri, 65211
Cedar Health Research
Dallas, Texas, 75251
Dothan Behavioral Medicine Clinic
Dothan, Alabama, 36303
Core Clinical Research
Everett, Washington, 98201
Research site
Lake Charles, Louisiana, 70629
Center for Psychiatry and Behavioral Medicine Inc.
Las Vegas, Nevada, 89128
The Lurie Center for Autism
Lexington, Massachusetts, 02421-3114
Alivation
Lincoln, Nebraska, 68526
Bioscience Research
Mount Kisco, New York, 10549
Access Clinical Trials
Nashville, Tennessee, 37203
Research site
New York, New York, 10036
Rutger's-New Jersey Medical Scholl Clinical Research Unit
Newark, New Jersey, 07103
The Holloway Group, Inc
Oklahoma City, Oklahoma, 73116
APG Research
Orlando, Florida, 32803
Southwest Autism Research and Resource Center
Phoenix, Arizona, 85006
For additional information regarding sites
Princeton, New Jersey, 08540
Finger Lakes Clinical Research
Rochester, New York, 14618
Research site
Saint Charles, Missouri, 63304
Research site
San Antonio, Texas, 78249
UT Health San Antonio Long School of Medicine, Department of Psychiatry and Behavioral Sciences
San Antonio, Texas, 78289
University of California San Francisco, Nancy Friend Pritzker Psychiatry
San Francisco, California, 94143-3132
Richmond Behavioral Associates
Staten Island, New York, 10314
Family Psychiatry of the Woodlands
The Woodlands, Texas, 77381
Woodstock Research Center
Woodstock, Vermont, 05091
About this study
Official title: A Phase 3, Multicenter, Open Label Trial to Evaluate the Long-term Safety and Tolerability of Brexpiprazole in Treatment of Children and Adolescents With Irritability Associated With Autism Spectrum Disorder
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.
- Being tested
- Brexpiprazole
- Keywords
- Autism, Autism Spectrum Disorder, ASD, Irritability
- Medical subject headings
- Autistic Disorder, Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrexpiprazoleDrug
Also called OPC-34712, LuAF41156
Oral tablet; taken once daily
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Brexpiprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
The ABC is 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=problem is moderately serious; 3=problem is severe in degree). The Irritability subscale (ABC-I) measures emotional and behavioral symptoms of ASD, including aggression toward others, deliberate self-injuriousness, temper tantrums, \& 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. Negative change from baseline indicates less symptoms.
Measured: Baseline (current study), Week 26
Mean Change From Baseline to Week 26 in Clinical Global Impression - Severity (CGI-S) Scale 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. The total score ranges from 0 to 7, where higher scores indicate worse condition. A negative change from baseline indicates less symptoms.
Measured: Baseline (current study), Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2020
- Study start23 Jan 2020
- Primary completion16 Mar 2023
- Study completion16 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Irritability Associated With Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04258839
- Sponsor's protocol ID
- 331-201-00191
- Other IDs
- 2018-004899-35, 2018
- Status last verified
- May 2024
- First submitted
- 4 Feb 2020
- Last updated
- 30 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Open Label Trial to Evaluate the Long-term Safety and Tolerability of Brexpiprazole in Treatment of Children and Adolescents With Irritability Associated With Autism Spectrum Disorder
- ClinicalTrials.gov ID
- NCT04258839
- Acronym / sponsor ID
- 331-201-00191
- Keywords
- Autism, Autism Spectrum Disorder, ASD, Irritability
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Study start
- 23 Jan 2020 (actual)
- Primary completion
- 16 Mar 2023 (actual)
- Study completion
- 16 Mar 2023 (actual)
- First posted
- 6 Feb 2020 (actual)
- Results
- Posted 30 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Brexpiprazole | Experimental | Drug: BrexpiprazoleParticipants 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. |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 5 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrexpiprazoleAlso: OPC-34712, LuAF41156Oral tablet; taken once daily | Drug | Brexpiprazole |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs
Time frame: 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)
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.
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs
Time frame: Baseline (current study) up to Week 26
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.
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities
Time frame: Baseline (current study) up to Week 26
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.
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities
Time frame: Baseline (current study) up to Week 26
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.
Number of Participants With Potentially Clinically Relevant Abnormal Physical Examination Values
Time frame: Baseline (current study) up to Week 26
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.
Number of Participants With Suicidality as Measured by Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Baseline (current study) up to Week 26
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.
Change From Baseline in Simpson Angus Scale (SAS) Total Score at Week 2
Time frame: Baseline and 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.
Change From Baseline in SAS Total Score at Week 14
Time frame: Baseline and 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.
Change From Baseline in SAS Total Score at Week 26
Time frame: Baseline and 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.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Week 2
Time frame: Baseline and 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.
Change From Baseline in AIMS Total Score at Week 14
Time frame: Baseline and 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.
Change From Baseline in AIMS Total Score at Week 26
Time frame: Baseline and 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.
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score at Week 2
Time frame: Baseline and 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.
Change From Baseline in BARS Score at Week 14
Time frame: Baseline and 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.
Change From Baseline in BARS Score at Week 26
Time frame: Baseline and 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.
Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 14
Time frame: Baseline 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.
Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 26
Time frame: Baseline 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.
Time to Discontinuation Due to AE
Time frame: Baseline (in current study) up to 21 days post last dose of study drug (up to approximately 29 weeks)
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.
2 secondary outcomes
Mean Change From Baseline to Week 26 in Aberrant Behavior Checklist - Irritability (ABC-I) Subscale Score
Time frame: Baseline (current study), Week 26
Mean Change From Baseline to Week 26 in Clinical Global Impression - Severity (CGI-S) Scale Score
Time frame: Baseline (current study), Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
28 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brexpiprazole in people with Irritability Associated With Autism Spectrum Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 28 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs (time frame: 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)). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2024.