Irritability Associated With Autism Spectrum Disorder
Conditions
Keywords
Autism, Autism Spectrum Disorder, ASD, Irritability
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.
Interventions
DRUGBrexpiprazole
Oral tablet; taken once daily
Sponsors
H. Lundbeck A/S
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Discontinuation Due to AE | 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. |
| Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 14 | 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 | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | 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 | 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 | 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 | 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 | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Week 26 in Clinical Global Impression - Severity (CGI-S) Scale Score | Baseline (current study), Week 26 | 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. |
| Mean Change From Baseline to Week 26 in Aberrant Behavior Checklist - Irritability (ABC-I) Subscale Score | Baseline (current study), Week 26 | 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. |
Countries
United States
Participant flow
Recruitment details
Participants with irritability associated with autism spectrum disorder (ASD) were enrolled in the study at sites in the United States from 23 January 2020 to 16 March 2023.
Pre-assignment details
A total of 95 eligible participants who completed 8-week, double-blind treatment, in the parent study 331-201-00148 (NCT04174365) and, who in the investigator's judgment, could potentially benefit from receiving brexpiprazole were enrolled in this study. Data was summarized as per the treatment received in the parent study 331-201-00148 (NCT04174365).
Participants by arm
| Arm | Count |
|---|---|
| Prior Brexpiprazole Participants who received brexpiprazole in the parent study 331-201-00148 (NCT04174365) received brexpiprazole based on the body weight for 26 weeks in this study.
Participants with body weight \< 50 kg, received brexpiprazole tablets orally, 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. | 49 |
| Prior Placebo Participants who received placebo matched to brexpiprazole in the parent study 331-201-00148 (NCT04174365) received brexpiprazole based on the body weight for 26 weeks in this study.
Participants with body weight \< 50 kg, received brexpiprazole tablets orally, 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 to 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. | 46 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Reason not Specified | 0 | 1 |
| Overall Study | Withdrawal by Caregiver | 5 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Prior Brexpiprazole | Prior Placebo | Total |
|---|---|---|---|
| Abnormal Involuntary Movement Scale (AIMS) Total Score | 0.06 score on a scale STANDARD_DEVIATION 0.32 | 0.02 score on a scale STANDARD_DEVIATION 0.15 | 0.04 score on a scale STANDARD_DEVIATION 0.25 |
| Age, Continuous | 10.0 years STANDARD_DEVIATION 3.1 | 10.0 years STANDARD_DEVIATION 3.1 | 10.0 years STANDARD_DEVIATION 3.1 |
| Barnes Akathisia Rating Scale (BARS) Score | 0.04 score on a scale STANDARD_DEVIATION 0.2 | 0.09 score on a scale STANDARD_DEVIATION 0.46 | 0.06 score on a scale STANDARD_DEVIATION 0.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 8 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 38 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Black or African American | 8 Participants | 2 Participants | 10 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Race White | 37 Participants | 38 Participants | 75 Participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 12 Participants |
| Sex: Female, Male Male | 45 Participants | 38 Participants | 83 Participants |
| Simpson Angus Scale (SAS) Score | 0.4 score on a scale STANDARD_DEVIATION 1.9 | 0.2 score on a scale STANDARD_DEVIATION 0.6 | 0.3 score on a scale STANDARD_DEVIATION 1.4 |
| Weight | 41.6 kilogram (kg) STANDARD_DEVIATION 17.9 | 44.2 kilogram (kg) STANDARD_DEVIATION 18.3 | 42.9 kilogram (kg) STANDARD_DEVIATION 18.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 46 |
| other Total, other adverse events | 17 / 49 | 11 / 46 |
| serious Total, serious adverse events | 2 / 49 | 1 / 46 |
Outcome results
Primary
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.
Time frame: Baseline and Week 2
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall Number of Participants Analyzed' indicates the number of participants with data available for outcome measure analysis at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Week 2 | 0.0 score on a scale | Standard Deviation 0 |
| Prior Placebo | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Week 2 | 0.14 score on a scale | Standard Deviation 1.08 |
Primary
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.
Time frame: Baseline and Week 14
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall Number of Participants Analyzed' indicates the number of participants with data available for outcome measure analysis at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Change From Baseline in AIMS Total Score at Week 14 | 0.0 score on a scale | Standard Deviation 0 |
| Prior Placebo | Change From Baseline in AIMS Total Score at Week 14 | 0.16 score on a scale | Standard Deviation 1.15 |
Primary
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.
Time frame: Baseline and Week 26
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall Number of Participants Analyzed' indicates the number of participants with data available for outcome measure analysis at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Change From Baseline in AIMS Total Score at Week 26 | 0.00 score on a scale | Standard Deviation 0 |
| Prior Placebo | Change From Baseline in AIMS Total Score at Week 26 | -0.04 score on a scale | Standard Deviation 0.19 |
Primary
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.
Time frame: Baseline and Week 2
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall Number of Participants Analyzed' indicates the number of participants with data available for outcome measure analysis at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score at Week 2 | 0.02 score on a scale | Standard Deviation 0.26 |
| Prior Placebo | Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score at Week 2 | 0.05 score on a scale | Standard Deviation 0.3 |
Primary
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.
Time frame: Baseline and Week 14
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall Number of Participants Analyzed' indicates the number of participants with data available for outcome measure analysis at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Change From Baseline in BARS Score at Week 14 | -0.05 score on a scale | Standard Deviation 0.22 |
| Prior Placebo | Change From Baseline in BARS Score at Week 14 | 0.05 score on a scale | Standard Deviation 0.4 |
Primary
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.
Time frame: Baseline and Week 26
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall Number of Participants Analyzed' indicates the number of participants with data available for outcome measure analysis at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Change From Baseline in BARS Score at Week 26 | 0.00 score on a scale | Standard Deviation 0.24 |
| Prior Placebo | Change From Baseline in BARS Score at Week 26 | -0.04 score on a scale | Standard Deviation 0.19 |
Primary
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.
Time frame: Baseline and Week 14
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall Number of Participants Analyzed' indicates the number of participants with data available for outcome measure analysis at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Change From Baseline in SAS Total Score at Week 14 | -0.1 score on a scale | Standard Deviation 0.7 |
| Prior Placebo | Change From Baseline in SAS Total Score at Week 14 | 0.2 score on a scale | Standard Deviation 0.6 |
Primary
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.
Time frame: Baseline and Week 26
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall Number of Participants Analyzed' indicates the number of participants with data available for outcome measure analysis at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Change From Baseline in SAS Total Score at Week 26 | -0.1 score on a scale | Standard Deviation 0.9 |
| Prior Placebo | Change From Baseline in SAS Total Score at Week 26 | -0.0 score on a scale | Standard Deviation 0.2 |
Primary
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.
Time frame: Baseline and Week 2
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Change From Baseline in Simpson Angus Scale (SAS) Total Score at Week 2 | -0.0 score on a scale | Standard Deviation 0.5 |
| Prior Placebo | Change From Baseline in Simpson Angus Scale (SAS) Total Score at Week 2 | 0.0 score on a scale | Standard Deviation 0.5 |
Primary
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.
Time frame: Baseline (current study) up to Week 26
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for this outcome measure. 'Number analyzed' indicates the number of participants with data available for analysis of the specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | SBP Standing (mmHg): High | 4 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | SBP Supine (mmHg): High | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | DBP Standing (mmHg): Low | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | DBP Standing (mmHg): High | 2 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | DBP Supine (mmHg): Low | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | DBP Supine (mmHg): High | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Heart Rate Standing (beats/min): High | 10 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Heart Rate Supine (beats/min): Low | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Heart Rate Supine (beats/min): High | 3 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Body Temperature | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Heart Rate Supine (beats/min): Low | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | SBP Standing (mmHg): High | 5 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | DBP Supine (mmHg): High | 3 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | SBP Supine (mmHg): High | 5 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Body Temperature | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | DBP Standing (mmHg): Low | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Heart Rate Standing (beats/min): High | 4 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | DBP Standing (mmHg): High | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Heart Rate Supine (beats/min): High | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | DBP Supine (mmHg): Low | 1 Participants |
Primary
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.
Time frame: Baseline (current study) up to Week 26
Population: Safety Sample included all enrolled participants who received at least one dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Abnormal Physical Examination Values | 6 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Abnormal Physical Examination Values | 4 Participants |
Primary
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.
Time frame: Baseline (current study) up to Week 26
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for this outcome measure. 'Number analyzed' indicates the number of participants with data available for the analysis of the specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Rate: Tachycardia | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Rate: Bradycardia | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Rhythm: Sinus Tachycardia | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Rhythm: Sinus Bradycardia | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Rhythm: Supraventricular Premature Beat | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Conduction: Right Bundle Branch Block | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | ST/T Morphology: Symmetrical T-Wave Inversion | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | ST/T Morphology: Symmetrical T-Wave Inversion | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Rate: Tachycardia | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Rhythm: Sinus Bradycardia | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Rate: Bradycardia | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Conduction: Right Bundle Branch Block | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Rhythm: Sinus Tachycardia | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities | Rhythm: Supraventricular Premature Beat | 0 Participants |
Primary
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.
Time frame: Baseline (current study) up to Week 26
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for this outcome measure. 'Number analyzed' indicates the number of participants with data available for analysis of the specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Neutrophils/Leukocytes (%): High | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Alanine Aminotransferase (U/L): High | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Aspartate Aminotransferase (U/L): High | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Bicarbonate (mEq/L): Low | 14 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Bilirubin (mg/dL): Low | 10 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Bilirubin (mg/dL): High | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Calcium (mg/dL): Low | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Chloride (mEq/L): High | 2 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Cortisol (ug/dL): Low | 7 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Creatinine (mg/dL): High | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Glucose (mg/dL): Low | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Glucose (mg/dL): High | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Potassium (mEq/L): High | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Sodium (mEq/L): High | 2 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Eosinophils/Leukocytes (%): High | 2 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Hematocrit (%): Low | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Hematocrit (%): High | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Hemoglobin (g/dL): Low | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Hemoglobin A1C (%): High | 2 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Leukocytes (10^9/L): Low | 6 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Leukocytes (10^9/L): High | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Neutrophils (10^9/L): High | 0 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Neutrophils/Leukocytes (%): Low | 8 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Activated Partial Thromboplastin Time (sec): High | 6 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Platelets (10^9/L): High | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Prothrombin Intl. Normalized Ratio: High | 5 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Prothrombin Time (sec): High | 3 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Protein, Urine: Low | 12 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Protein, Urine: High | 10 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Prolactin (ng/mL): Low | 3 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Prolactin (ng/mL): High | 1 Participants |
| Prior Brexpiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Thyrotropin (uIU/mL): High | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Neutrophils/Leukocytes (%): High | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Activated Partial Thromboplastin Time (sec): High | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Hematocrit (%): High | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Alanine Aminotransferase (U/L): High | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Thyrotropin (uIU/mL): High | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Aspartate Aminotransferase (U/L): High | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Hemoglobin (g/dL): Low | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Bicarbonate (mEq/L): Low | 15 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Platelets (10^9/L): High | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Bilirubin (mg/dL): Low | 8 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Hemoglobin A1C (%): High | 4 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Bilirubin (mg/dL): High | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Protein, Urine: High | 11 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Calcium (mg/dL): Low | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Leukocytes (10^9/L): Low | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Chloride (mEq/L): High | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Prothrombin Intl. Normalized Ratio: High | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Cortisol (ug/dL): Low | 9 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Leukocytes (10^9/L): High | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Creatinine (mg/dL): High | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Protein, Urine: Low | 11 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Glucose (mg/dL): Low | 1 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Prolactin (ng/mL): High | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Glucose (mg/dL): High | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Neutrophils (10^9/L): High | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Potassium (mEq/L): High | 3 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Prothrombin Time (sec): High | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Sodium (mEq/L): High | 0 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Neutrophils/Leukocytes (%): Low | 2 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Eosinophils/Leukocytes (%): High | 3 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Prolactin (ng/mL): Low | 4 Participants |
| Prior Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities | Hematocrit (%): Low | 1 Participants |
Primary
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.
Time frame: Baseline (current study) up to Week 26
Population: Safety Sample included all enrolled participants who received at least one dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prior Brexpiprazole | Number of Participants With Suicidality as Measured by Columbia-Suicide Severity Rating Scale (C-SSRS) | 4 Participants |
| Prior Placebo | Number of Participants With Suicidality as Measured by Columbia-Suicide Severity Rating Scale (C-SSRS) | 2 Participants |
Primary
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.
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)
Population: Safety Sample included all enrolled participants who received at least one dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior Brexpiprazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With TEAEs | 23 Participants |
| Prior Brexpiprazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With Mild TEAEs | 15 Participants |
| Prior Brexpiprazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With Moderate TEAEs | 11 Participants |
| Prior Brexpiprazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With Severe TEAEs | 2 Participants |
| Prior Brexpiprazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With Serious TEAEs | 2 Participants |
| Prior Brexpiprazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With Trial Discontinuations due to TEAEs | 2 Participants |
| Prior Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With Serious TEAEs | 1 Participants |
| Prior Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With TEAEs | 24 Participants |
| Prior Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With Severe TEAEs | 2 Participants |
| Prior Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With Mild TEAEs | 19 Participants |
| Prior Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With Trial Discontinuations due to TEAEs | 4 Participants |
| Prior Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs | Participants With Moderate TEAEs | 12 Participants |
Primary
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.
Time frame: Baseline up to Week 14
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall Number of Participants Analyzed' indicates the number of participants with data available for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prior Brexpiprazole | Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 14 | Weight Gain >= 7% | 45.0 percentage of participants |
| Prior Brexpiprazole | Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 14 | Weight Loss >= 7% | 0.0 percentage of participants |
| Prior Placebo | Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 14 | Weight Loss >= 7% | 0.0 percentage of participants |
| Prior Placebo | Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 14 | Weight Gain >= 7% | 48.6 percentage of participants |
Primary
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.
Time frame: Baseline up to Week 26
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prior Brexpiprazole | Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 26 | Weight Gain >= 7% | 71.8 percentage of participants |
| Prior Brexpiprazole | Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 26 | Weight Loss >= 7% | 0.0 percentage of participants |
| Prior Placebo | Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 26 | Weight Gain >= 7% | 76.7 percentage of participants |
| Prior Placebo | Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 26 | Weight Loss >= 7% | 3.3 percentage of participants |
Primary
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.
Time frame: Baseline (in current study) up to 21 days post last dose of study drug (up to approximately 29 weeks)
Population: Safety Sample included all enrolled participants who received at least one dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior Brexpiprazole | Time to Discontinuation Due to AE | 83 days |
| Prior Placebo | Time to Discontinuation Due to AE | 113 days |
Secondary
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.
Time frame: Baseline (current study), Week 26
Population: Efficacy Sample included all participants in the Safety Sample who had a baseline assessment and at least one post-baseline assessment of the ABC-I subscale score. 'Overall number of participants analyzed' indicates the number of participants with data available for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline to Week 26 in Aberrant Behavior Checklist - Irritability (ABC-I) Subscale Score | -5.47 score on a scale | Standard Deviation 8.06 |
| Prior Placebo | Mean Change From Baseline to Week 26 in Aberrant Behavior Checklist - Irritability (ABC-I) Subscale Score | -7.00 score on a scale | Standard Deviation 8.36 |
Secondary
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.
Time frame: Baseline (current study), Week 26
Population: Efficacy Sample included all participants in the Safety Sample who had a baseline assessment and at least one post-baseline assessment of the ABC-I subscale score. 'Overall number of participants analyzed' indicates the number of participants with data available for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline to Week 26 in Clinical Global Impression - Severity (CGI-S) Scale Score | -0.78 score on a scale | Standard Deviation 0.99 |
| Prior Placebo | Mean Change From Baseline to Week 26 in Clinical Global Impression - Severity (CGI-S) Scale Score | -0.68 score on a scale | Standard Deviation 0.94 |