Trial Outcomes & Findings for Brexpiprazole in Treatment of Children and Adolescents With Irritability Associated With Autism Spectrum Disorder for Subjects That Have Completed Participation in 331-201-00148 (NCT NCT04258839)

NCT ID: NCT04258839

Last Updated: 2024-05-30

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 95 participants
• Primary outcome timeframe: 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)
• Results posted on: 2024-05-30

Participant Flow

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.

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).

Participant milestones

Measure	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 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.	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.
Overall Study STARTED	49	46
Overall Study Safety Sample	49	46
Overall Study Efficacy Sample	48	46
Overall Study COMPLETED	39	31
Overall Study NOT COMPLETED	10	15

Reasons for withdrawal

Measure	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 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.	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.
Overall Study Adverse Event	2	4
Overall Study Lack of Efficacy	0	2
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	1	2
Overall Study Withdrawal by Caregiver	5	6
Overall Study Reason not Specified	0	1

Baseline Characteristics

Safety Sample included all enrolled participants who received at least one dose of IMP. 'Number analyzed' indicates the number of participants with data available for measure analysis.

Baseline characteristics by cohort

Measure	Prior Brexpiprazole n=49 Participants 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.	Prior Placebo n=46 Participants 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.	Total n=95 Participants Total of all reporting groups
Age, Continuous	10.0 years STANDARD_DEVIATION 3.1 • n=49 Participants	10.0 years STANDARD_DEVIATION 3.1 • n=46 Participants	10.0 years STANDARD_DEVIATION 3.1 • n=95 Participants
Sex: Female, Male Female	4 Participants n=49 Participants	8 Participants n=46 Participants	12 Participants n=95 Participants
Sex: Female, Male Male	45 Participants n=49 Participants	38 Participants n=46 Participants	83 Participants n=95 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=49 Participants	8 Participants n=46 Participants	14 Participants n=95 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=49 Participants	38 Participants n=46 Participants	81 Participants n=95 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=49 Participants	0 Participants n=46 Participants	0 Participants n=95 Participants
Race/Ethnicity, Customized Race · White	37 Participants n=49 Participants	38 Participants n=46 Participants	75 Participants n=95 Participants
Race/Ethnicity, Customized Race · Black or African American	8 Participants n=49 Participants	2 Participants n=46 Participants	10 Participants n=95 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=49 Participants	3 Participants n=46 Participants	4 Participants n=95 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=49 Participants	1 Participants n=46 Participants	1 Participants n=95 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=49 Participants	2 Participants n=46 Participants	5 Participants n=95 Participants
Weight	41.6 kilogram (kg) STANDARD_DEVIATION 17.9 • n=49 Participants	44.2 kilogram (kg) STANDARD_DEVIATION 18.3 • n=46 Participants	42.9 kilogram (kg) STANDARD_DEVIATION 18.1 • n=95 Participants
Simpson Angus Scale (SAS) Score	0.4 score on a scale STANDARD_DEVIATION 1.9 • n=48 Participants • Safety Sample included all enrolled participants who received at least one dose of IMP. 'Number analyzed' indicates the number of participants with data available for measure analysis.	0.2 score on a scale STANDARD_DEVIATION 0.6 • n=46 Participants • Safety Sample included all enrolled participants who received at least one dose of IMP. 'Number analyzed' indicates the number of participants with data available for measure analysis.	0.3 score on a scale STANDARD_DEVIATION 1.4 • n=94 Participants • Safety Sample included all enrolled participants who received at least one dose of IMP. 'Number analyzed' indicates the number of participants with data available for measure analysis.
Abnormal Involuntary Movement Scale (AIMS) Total Score	0.06 score on a scale STANDARD_DEVIATION 0.32 • n=48 Participants • Safety Sample included all enrolled participants who received at least one dose of IMP. 'Number analyzed' indicates the number of participants with data available for measure analysis.	0.02 score on a scale STANDARD_DEVIATION 0.15 • n=46 Participants • Safety Sample included all enrolled participants who received at least one dose of IMP. 'Number analyzed' indicates the number of participants with data available for measure analysis.	0.04 score on a scale STANDARD_DEVIATION 0.25 • n=94 Participants • Safety Sample included all enrolled participants who received at least one dose of IMP. 'Number analyzed' indicates the number of participants with data available for measure analysis.
Barnes Akathisia Rating Scale (BARS) Score	0.04 score on a scale STANDARD_DEVIATION 0.20 • n=48 Participants • Safety Sample included all enrolled participants who received at least one dose of IMP. 'Number analyzed' indicates the number of participants with data available for measure analysis.	0.09 score on a scale STANDARD_DEVIATION 0.46 • n=46 Participants • Safety Sample included all enrolled participants who received at least one dose of IMP. 'Number analyzed' indicates the number of participants with data available for measure analysis.	0.06 score on a scale STANDARD_DEVIATION 0.35 • n=94 Participants • Safety Sample included all enrolled participants who received at least one dose of IMP. 'Number analyzed' indicates the number of participants with data available for measure analysis.

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=49 Participants 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.	Prior Placebo n=46 Participants 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.
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	24 Participants
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	19 Participants
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	12 Participants
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	2 Participants
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	1 Participants
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	4 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=48 Participants 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.	Prior Placebo n=46 Participants 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.
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs SBP Standing (mmHg): High	4 Participants	5 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs SBP Supine (mmHg): High	1 Participants	5 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs DBP Standing (mmHg): Low	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs DBP Standing (mmHg): High	2 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs DBP Supine (mmHg): Low	1 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs DBP Supine (mmHg): High	1 Participants	3 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Heart Rate Standing (beats/min): High	10 Participants	4 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Heart Rate Supine (beats/min): Low	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Heart Rate Supine (beats/min): High	3 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Body Temperature	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=45 Participants 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.	Prior Placebo n=43 Participants 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.
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities Rate: Tachycardia	1 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities Rate: Bradycardia	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities Rhythm: Sinus Tachycardia	1 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities Rhythm: Sinus Bradycardia	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities Rhythm: Supraventricular Premature Beat	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities Conduction: Right Bundle Branch Block	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities ST/T Morphology: Symmetrical T-Wave Inversion	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=42 Participants 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.	Prior Placebo n=42 Participants 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.
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Activated Partial Thromboplastin Time (sec): High	6 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Alanine Aminotransferase (U/L): High	0 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Aspartate Aminotransferase (U/L): High	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Bicarbonate (mEq/L): Low	14 Participants	15 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Bilirubin (mg/dL): Low	10 Participants	8 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Bilirubin (mg/dL): High	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Calcium (mg/dL): Low	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Chloride (mEq/L): High	2 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Cortisol (ug/dL): Low	7 Participants	9 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Creatinine (mg/dL): High	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Glucose (mg/dL): Low	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Glucose (mg/dL): High	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Potassium (mEq/L): High	1 Participants	3 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Sodium (mEq/L): High	2 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Eosinophils/Leukocytes (%): High	2 Participants	3 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Hematocrit (%): Low	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Hematocrit (%): High	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Hemoglobin (g/dL): Low	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Hemoglobin A1C (%): High	2 Participants	4 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Leukocytes (10^9/L): Low	6 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Leukocytes (10^9/L): High	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Neutrophils (10^9/L): High	0 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Neutrophils/Leukocytes (%): Low	8 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Neutrophils/Leukocytes (%): High	0 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Platelets (10^9/L): High	1 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Prothrombin Intl. Normalized Ratio: High	5 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Prothrombin Time (sec): High	3 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Protein, Urine: Low	12 Participants	11 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Protein, Urine: High	10 Participants	11 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Prolactin (ng/mL): Low	3 Participants	4 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Prolactin (ng/mL): High	1 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities Thyrotropin (uIU/mL): High	2 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (current study) up to Week 26

Population: Safety Sample included all enrolled participants who received at least one dose of IMP.

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.

Outcome measures

Measure	Prior Brexpiprazole n=49 Participants 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.	Prior Placebo n=46 Participants 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.
Number of Participants With Potentially Clinically Relevant Abnormal Physical Examination Values	6 Participants	4 Participants

PRIMARY outcome

Timeframe: Baseline (current study) up to Week 26

Population: Safety Sample included all enrolled participants who received at least one dose of IMP.

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.

Outcome measures

Measure	Prior Brexpiprazole n=49 Participants 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.	Prior Placebo n=46 Participants 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.
Number of Participants With Suicidality as Measured by Columbia-Suicide Severity Rating Scale (C-SSRS)	4 Participants	2 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=45 Participants 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.	Prior Placebo n=41 Participants 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.
Change From Baseline in Simpson Angus Scale (SAS) Total Score at Week 2	-0.0 score on a scale Standard Deviation 0.5	0.0 score on a scale Standard Deviation 0.5

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=38 Participants 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.	Prior Placebo n=37 Participants 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.
Change From Baseline in SAS Total Score at Week 14	-0.1 score on a scale Standard Deviation 0.7	0.2 score on a scale Standard Deviation 0.6

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=36 Participants 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.	Prior Placebo n=28 Participants 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.
Change From Baseline in SAS Total Score at Week 26	-0.1 score on a scale Standard Deviation 0.9	-0.0 score on a scale Standard Deviation 0.2

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=45 Participants 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.	Prior Placebo n=43 Participants 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.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Week 2	0.0 score on a scale Standard Deviation 0.00	0.14 score on a scale Standard Deviation 1.08

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=40 Participants 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.	Prior Placebo n=38 Participants 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.
Change From Baseline in AIMS Total Score at Week 14	0.0 score on a scale Standard Deviation 0.00	0.16 score on a scale Standard Deviation 1.15

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=36 Participants 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.	Prior Placebo n=28 Participants 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.
Change From Baseline in AIMS Total Score at Week 26	0.00 score on a scale Standard Deviation 0.00	-0.04 score on a scale Standard Deviation 0.19

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=45 Participants 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.	Prior Placebo n=43 Participants 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.
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score at Week 2	0.02 score on a scale Standard Deviation 0.26	0.05 score on a scale Standard Deviation 0.30

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=40 Participants 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.	Prior Placebo n=38 Participants 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.
Change From Baseline in BARS Score at Week 14	-0.05 score on a scale Standard Deviation 0.22	0.05 score on a scale Standard Deviation 0.40

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=36 Participants 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.	Prior Placebo n=28 Participants 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.
Change From Baseline in BARS Score at Week 26	0.00 score on a scale Standard Deviation 0.24	-0.04 score on a scale Standard Deviation 0.19

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=40 Participants 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.	Prior Placebo n=37 Participants 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.
Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 14 Weight Gain >= 7%	45.0 percentage of participants	48.6 percentage of participants
Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 14 Weight Loss >= 7%	0.0 percentage of participants	0.0 percentage of participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=39 Participants 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.	Prior Placebo n=30 Participants 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.
Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 26 Weight Gain >= 7%	71.8 percentage of participants	76.7 percentage of participants
Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 26 Weight Loss >= 7%	0.0 percentage of participants	3.3 percentage of participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=2 Participants 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.	Prior Placebo n=4 Participants 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.
Time to Discontinuation Due to AE	83 days Interval 14.0 to 152.0	113 days Interval 54.0 to 140.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=35 Participants 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.	Prior Placebo n=27 Participants 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.
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	-7.00 score on a scale Standard Deviation 8.36

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Prior Brexpiprazole n=36 Participants 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.	Prior Placebo n=28 Participants 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.
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	-0.68 score on a scale Standard Deviation 0.94

Adverse Events

Prior Brexpiprazole

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Prior Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Prior Brexpiprazole n=49 participants at risk 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.	Prior Placebo n=46 participants at risk 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.
Nervous system disorders Dyskinesia	2.0% 1/49 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.	0.00% 0/46 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.
Psychiatric disorders Affective Disorder	0.00% 0/49 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.	2.2% 1/46 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.
Psychiatric disorders Suicidal Ideation	2.0% 1/49 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.	0.00% 0/46 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.

Other adverse events

Measure	Prior Brexpiprazole n=49 participants at risk 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.	Prior Placebo n=46 participants at risk 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.
Infections and infestations Gastroenteritis	6.1% 3/49 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.	0.00% 0/46 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.
Infections and infestations Viral Influenza	8.2% 4/49 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.	0.00% 0/46 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.
Investigations Weight Increased	10.2% 5/49 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.	17.4% 8/46 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.
Metabolism and nutrition disorders Increased Appetite	4.1% 2/49 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.	8.7% 4/46 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.
Nervous system disorders Somnolence	10.2% 5/49 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.	2.2% 1/46 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.
Psychiatric disorders Irritability	6.1% 3/49 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.	0.00% 0/46 • 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) Safety Sample included all enrolled participants who received at least one dose of IMP.

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: 1-609-524-6788

Email: clinicaltransparency@otsuka-us.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place