Trial Outcomes & Findings for Trial to Evaluate the Short-term Safety & Efficacy of Brexpiprazole Monotherapy in the Treatment of Adolescents With Schizophrenia (NCT NCT03198078)

NCT ID: NCT03198078

Last Updated: 2023-12-20

Results Overview

The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) to 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranges from 30 (best possible outcome) to 210 (worst possible outcome). Higher scores indicate worsening of symptoms. Least squares (LS) mean was determined by Mixed-effect model repeated measures (MMRM) method with fixed effect of treatment, (pooled) clinical center visit, treatment visit interaction, baseline value and baseline visit interaction as a covariate, and with an unstructured covariance.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 316 participants
• Primary outcome timeframe: Baseline to Week 6
• Results posted on: 2023-12-20

Participant Flow

Participants took part in the study at investigational sites in the United States, Mexico, France, Italy, Poland, Romania, Serbia, Spain, Ukraine, and Russia from 30 June 2017 to 03 April 2023.

A total of 376 participants were screened, of which 316 participants were enrolled and randomized to brexpiprazole, aripiprazole or placebo groups in 1:1:1 ratio.

Participant milestones

Measure	Brexpiprazole Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Overall Study STARTED	110	102	104
Overall Study Safety Sample	110	102	104
Overall Study Efficacy Sample	110	101	103
Overall Study COMPLETED	107	97	92
Overall Study NOT COMPLETED	3	5	12

Reasons for withdrawal

Measure	Brexpiprazole Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Overall Study Adverse Event	0	1	2
Overall Study Lack of Efficacy	0	0	3
Overall Study Lost to Follow-up	1	0	0
Overall Study Pregnancy	0	1	0
Overall Study Withdrawal by Subject	1	0	2
Overall Study Withdrawal by Caregiver	1	3	5

Baseline Characteristics

Trial to Evaluate the Short-term Safety & Efficacy of Brexpiprazole Monotherapy in the Treatment of Adolescents With Schizophrenia

Baseline characteristics by cohort

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=102 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=104 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.	Total n=316 Participants Total of all reporting groups
Region of Enrollment Romania	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	18 participants n=4 Participants
Region of Enrollment Russia	4 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment Serbia	11 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants	31 participants n=4 Participants
Region of Enrollment Spain	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment Ukraine	35 participants n=5 Participants	33 participants n=7 Participants	34 participants n=5 Participants	102 participants n=4 Participants
Age, Continuous	15.3 years STANDARD_DEVIATION 1.5 • n=5 Participants	15.3 years STANDARD_DEVIATION 1.4 • n=7 Participants	15.2 years STANDARD_DEVIATION 1.4 • n=5 Participants	15.3 years STANDARD_DEVIATION 1.5 • n=4 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	57 Participants n=7 Participants	51 Participants n=5 Participants	166 Participants n=4 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	45 Participants n=7 Participants	53 Participants n=5 Participants	150 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	70 Participants n=5 Participants	66 Participants n=7 Participants	68 Participants n=5 Participants	204 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	8 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	21 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	29 Participants n=5 Participants	27 Participants n=7 Participants	25 Participants n=5 Participants	81 Participants n=4 Participants
Race/Ethnicity, Customized Race · Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	34 Participants n=5 Participants	32 Participants n=7 Participants	34 Participants n=5 Participants	100 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	75 Participants n=5 Participants	70 Participants n=7 Participants	68 Participants n=5 Participants	213 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	15 participants n=5 Participants	14 participants n=7 Participants	14 participants n=5 Participants	43 participants n=4 Participants
Region of Enrollment France	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment Italy	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment Mexico	32 participants n=5 Participants	31 participants n=7 Participants	32 participants n=5 Participants	95 participants n=4 Participants
Region of Enrollment Poland	5 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	11 participants n=4 Participants
Positive and Negative Syndrome Scale (PANSS) Total Score	101.1 score on a scale STANDARD_DEVIATION 14.9 • n=5 Participants	101.0 score on a scale STANDARD_DEVIATION 13.0 • n=7 Participants	102.1 score on a scale STANDARD_DEVIATION 16.3 • n=5 Participants	101.4 score on a scale STANDARD_DEVIATION 14.7 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy sample included all randomized participants who received at least 1 dose of IMP, had a baseline assessment, and at least one post-baseline assessment of the PANSS Total Score.

The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) to 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranges from 30 (best possible outcome) to 210 (worst possible outcome). Higher scores indicate worsening of symptoms. Least squares (LS) mean was determined by Mixed-effect model repeated measures (MMRM) method with fixed effect of treatment, (pooled) clinical center visit, treatment visit interaction, baseline value and baseline visit interaction as a covariate, and with an unstructured covariance.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score	-22.75 score on a scale Standard Error 1.49	-23.95 score on a scale Standard Error 1.57	-17.42 score on a scale Standard Error 1.58

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy sample included all randomized participants who received at least 1 dose of IMP, had a baseline assessment, and at least one post-baseline assessment of the PANSS Total Score.

PANSS has 7 positive symptom constructs: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, hostility; and 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. Each item's severity was rated on 7-point scale, with score of 1 (absence of symptoms) to 7 (extremely severe symptoms). PANSS positive & negative subscale scores were the sum of rating scores for 7 positive & 7 negative items respectively. Both scores range from 7 (best possible outcome) to 49 (worst possible outcome). Higher scores denote worsening of symptoms. LS mean was determined by MMRM method with fixed effect of treatment, (pooled) clinical center visit, treatment visit interaction, baseline value, and baseline visit interaction as a covariate, and with an unstructured covariance.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Change From Baseline to Week 6 in PANSS Positive and Negative Sub-Scales Scores Change From Baseline to Week 6 in PANSS Positive Sub-scale Score	-6.58 score on a scale Standard Error 0.43	-7.29 score on a scale Standard Error 0.45	-5.14 score on a scale Standard Error 0.46
Change From Baseline to Week 6 in PANSS Positive and Negative Sub-Scales Scores Change From Baseline to Week 6 in PANSS Negative Sub-scale Score	-4.70 score on a scale Standard Error 0.41	-4.77 score on a scale Standard Error 0.43	-3.82 score on a scale Standard Error 0.44

SECONDARY outcome

Timeframe: Up to 6 weeks

Population: Efficacy sample included all randomized participants who received at least 1 dose of IMP, had a baseline assessment, and at least one post-baseline assessment of the PANSS Total Score. Percentages are rounded off to the nearest decimal point.

Response was defined as at least 30% improvement from baseline in PANSS Total Score or CGI score of 1 or 2. The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel, and ranges from 30 (best possible outcome) to 210 (worst possible outcome). The CGI scale is an investigator-rated evaluation that assesses the severity of a participant's illness on a 7-point scale, ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Percentage of participants achieving response was determined by Last Observation Carried Forward (LOCF) method.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Percentage of Participants Achieving Response	43.64 percentage of participants	43.56 percentage of participants	28.16 percentage of participants

SECONDARY outcome

Timeframe: Up to 6 weeks

Population: Efficacy sample included all randomized participants who received at least 1 dose of IMP, had a baseline assessment, and at least one post-baseline assessment of the PANSS Total Score. Percentages are rounded off to the nearest decimal point.

Remission was defined as a score of ≤ 3 on each of the following specific PANSS items: delusions (positive scale item [P] 1), unusual thought content (general scale item [G] 9), hallucinatory behavior (P3), conceptual disorganization (P2), mannerisms/posturing (G5), blunted affect (negative scale item [N] 1), passive/apathetic social withdrawal (N4), and lack of spontaneity and conversation flow (N6). Each item's severity was rated on 7-point scale, with score of 1 (absence of symptoms) to 7 (extremely severe symptoms). Percentage of participants achieving remission was determined by LOCF method.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Percentage of Participants Achieving Remission	29.09 percentage of participants	35.64 percentage of participants	23.30 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy sample included all randomized participants who received at least 1 dose of IMP, had a baseline assessment, and at least one post-baseline assessment of the PANSS Total Score.

The CGAS is a 100-point rating scale measuring psychological, social, and school functioning for children aged 6-17 years and provides a global measure of the severity of disturbance. The scale is separated into 10-point sections that are headed with a description of the level of functioning and followed by examples matching the interval. The score ranges from 0-100, 1 to 10 indicates the need for constant supervision and 91 to 100 indicates superior functioning in all areas. Higher scores indicate better functioning. LS mean was determined by MMRM method with fixed effect of treatment, (pooled) clinical center visit, treatment visit interaction, baseline value, and baseline visit interaction as a covariate, and with an unstructured covariance.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Change From Baseline to Week 6 in Children's Global Assessment Scale (CGAS) Total Score	10.56 score on a scale Standard Error 1.00	12.07 score on a scale Standard Error 1.05	8.08 score on a scale Standard Error 1.06

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy sample included all randomized participants who received at least 1 dose of IMP, had a baseline assessment, and at least one post-baseline assessment of the PANSS Total Score.

The CGI-S scale is an investigator-rated evaluation that assesses the severity of a participant's illness on a 7-point scale, ranging from 1 to 7. The investigator answered the question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?". 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 participants. Higher scores indicate worse condition. LS mean was determined by the MMRM method with fixed effect of treatment, (pooled) clinical center visit, treatment visit interaction, baseline value, and baseline visit interaction as a covariate, and with an unstructured covariance.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Change From Baseline to Week 6 in Clinical Global Impression Severity (CGI-S) Scale Score	-0.92 score on a scale Standard Error 0.09	-1.01 score on a scale Standard Error 0.09	-0.80 score on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Week 6

Population: Efficacy sample included all randomized participants who received at least 1 dose of IMP, had a baseline assessment, and at least one post-baseline assessment of the PANSS Total Score.

The efficacy of brexpiprazole in the treatment was rated for each participant using the CGI-I. The investigator rated the participant's total improvement whether or not it was entirely due to drug treatment on a 7-point scale, ranging from 0 to 7. Response choices were: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Higher scores indicate worse condition. Mean CGI-I scale score was determined by LOCF method.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Mean Clinical Global Impression Improvement (CGI-I) Scale Score at Week 6	2.86 score on a scale Standard Deviation 0.95	2.79 score on a scale Standard Deviation 0.97	3.17 score on a scale Standard Deviation 1.08

SECONDARY outcome

Timeframe: From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP.

An AE was defined as any untoward medical occurrence in a participant administered with a medicinal product that does not necessarily have a causal relationship with the treatment.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=102 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=104 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Number of Participants With Adverse Events (AEs) and Trial Discontinuation Due to AEs AEs	46 Participants	56 Participants	44 Participants
Number of Participants With Adverse Events (AEs) and Trial Discontinuation Due to AEs Trial Discontinuation Due to AEs	0 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP.

An AE was defined as any untoward medical occurrence in a participant administered with a medicinal product that does not necessarily have a causal relationship with the treatment. An SAE was any AE that results in the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions which is 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. TEAE is any AE after the start of treatment or if the event was continuous from baseline, medicinal product related, or resulted in death, discontinuation, interruption or reduction of medicinal product. TEAEs were graded on a 3-point scale: 1 (Mild: Discomfort noticed, but no disruption to daily activity), 2 (Moderate: Discomfort sufficient to reduce or affect normal daily activity), and 3 (Severe: Inability to work or perform normal daily activity).

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=102 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=104 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Number of Participants With Treatment-emergent AEs (TEAEs), Serious TEAEs, and TEAEs Graded by Severity TEAEs	44 Participants	53 Participants	42 Participants
Number of Participants With Treatment-emergent AEs (TEAEs), Serious TEAEs, and TEAEs Graded by Severity Serious TEAEs	1 Participants	1 Participants	3 Participants
Number of Participants With Treatment-emergent AEs (TEAEs), Serious TEAEs, and TEAEs Graded by Severity Mild TEAEs	33 Participants	47 Participants	32 Participants
Number of Participants With Treatment-emergent AEs (TEAEs), Serious TEAEs, and TEAEs Graded by Severity Moderate TEAEs	17 Participants	16 Participants	13 Participants
Number of Participants With Treatment-emergent AEs (TEAEs), Serious TEAEs, and TEAEs Graded by Severity Severe TEAEs	2 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to last visit (approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.

Change in weight was reported, in kilograms (kg).

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Mean Change From Baseline in Weight	0.8 kg Standard Deviation 2.6	0.5 kg Standard Deviation 2.7	0.0 kg Standard Deviation 2.2

SECONDARY outcome

Timeframe: Baseline up to last visit (approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for the outcome measure analysis.

Change in height was reported in centimeters (cm).

Outcome measures

Measure	Brexpiprazole n=108 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=99 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=96 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Mean Change From Baseline in Height	0.2 cm Standard Deviation 1.1	0.2 cm Standard Deviation 2.9	0.3 cm Standard Deviation 0.6

SECONDARY outcome

Timeframe: Baseline up to last visit (approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP. 'Overall number of participants analyzed indicates the number of participants with data available for outcome measure analysis.

Change in BMI was reported in kilograms per square meter (kg/m^2).

Outcome measures

Measure	Brexpiprazole n=108 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=99 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=96 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Mean Change From Baseline in Body Mass Index (BMI)	0.2 kg/m^2 Standard Deviation 1.1	0.3 kg/m^2 Standard Deviation 1.5	0.0 kg/m^2 Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline up to last visit (approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis at the specified time point.

Change in waist circumference was reported in 'cm'.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Mean Change From Baseline in Waist Circumference	0.6 cm Standard Deviation 3.9	-0.3 cm Standard Deviation 4.3	0.0 cm Standard Deviation 5.1

SECONDARY outcome

Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP.

C-SSRS is a scale used to report at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any of the following items: actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior. The suicidal ideation total score is the sum of intensity scores of 5 items (frequency, duration, controllability, deterrents, and reasons for ideation). The score of each intensity item ranges from 0 (none) to 5 (worst) and the total score ranges from 0 to 25. Lower scores indicate improvement.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=102 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=104 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Number of Participants With At Least One Occurrence of Suicidal Behavior or Suicidal Ideation as Recorded on Columbia-Suicide Severity Rating Scale (C-SSRS)	1 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for the outcome measure analysis. 'Number analyzed' indicates the number of participants with at least one post-baseline numeric result for the specified parameter.

Potentially clinically relevant laboratory values assessed included - serum chemistry [including blinded prolactin], hematology, and urinalysis as defined in SAP.

Outcome measures

Measure	Brexpiprazole n=105 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=98 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=99 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Alanine Aminotransferase (U/L): High	1 Participants	2 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Bilirubin (mg/dL): High	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Cholesterol, Fasting (mg/dL): High	2 Participants	3 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Creatine kinase (U/L): High	5 Participants	4 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Glucose, Fasting (mg/dL): High	16 Participants	15 Participants	9 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values HDL Cholesterol, Fasting (mg/dL): Low	12 Participants	10 Participants	13 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values LDL Cholesterol, Fasting (mg/dL): High	2 Participants	3 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Triglycerides, Fasting (mg/dL): High	13 Participants	7 Participants	10 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Urate (mg/dL): High	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Eosinophils/Leukocytes (%): High	2 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Hematocrit (%): Low	4 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Hemoglobin (g/dL): Low	2 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Leukocytes (10^9/L): Low	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Leukocytes (10^9/L): High	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Protein, Urine: High	2 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with at least one post-baseline result for the specified vital signs.

Vital sign measurements included body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Blood pressure measurements were made in the supine, sitting, and standing positions after the participant had been in each position for at least 3 minutes as defined in SAP.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs SBP Sitting (mmHg): Low	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs SBP Standing (mmHg): Low	1 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs SBP Supine (mmHg): Low	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs DBP Standing (mmHg): Low	1 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs DBP Supine (mmHg): Low	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Weight (kg): Low	5 Participants	2 Participants	4 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Weight (kg): High	9 Participants	5 Participants	5 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Orthostatic Hypotension (mmHg): Low	2 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for the outcome measure analysis. 'Number analyzed' indicates the number of participants with at least one post-baseline numeric result for the specified parameter.

Twelve-lead ECG recordings were obtained after the participant was supine and at rest for at least 5 minutes as defined in SAP.

Outcome measures

Measure	Brexpiprazole n=107 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=97 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=94 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters Rate: Bradycardia	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters Rhythm: Sinus Bradycardia	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters Rhythm: Supraventricular Premature Beat	0 Participants	1 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters Rhythm: Ventricular Premature Beat	1 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters ST/T Morphology: QTcF	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters ST/T Morphology: QTcN	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to last visit (approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for the outcome measure analysis.

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 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 lower scores indicate less severe condition. LS mean was determined by Analysis of Covariance (ANCOVA) model with treatment and study center as main effects and baseline value as covariate.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Change From Baseline in Simpson Angus Scale (SAS) Total Score	0.04 score on a scale Standard Error 0.12	0.15 score on a scale Standard Error 0.12	-0.03 score on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline up to last visit (approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for the outcome measure analysis.

The AIMS assessment consists of 12 items rating the involuntary movements: Facial and oral movements (4 items), extremity movements (2 items), and trunk movements (1 item) were observed unobtrusively while the participant is at rest and the investigator also made global judgments on the participant's dyskinesias (2 items), and dental status (2 items). Severity of each item was rated on a 5-point scale, with a score of 0 (absence of symptoms) to 4 (severe condition). Total Score is the sum of the scores of all 12 items, ranging from 0 to 48, higher scores indicate severe condition. LS mean was determined by ANCOVA model with treatment and study center as main effects and baseline value as covariate.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score	-0.12 score on a scale Standard Deviation 0.09	0.05 score on a scale Standard Deviation 0.09	-0.06 score on a scale Standard Deviation 0.09

SECONDARY outcome

Timeframe: Baseline up to last visit (approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP. 'Overall number of participants analyzed' indicates the number of participants with data available for the outcome measure analysis.

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 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, higher scores indicate severe condition. LS mean was determined by ANCOVA model with treatment and study center as main effects and baseline value as covariate.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=101 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=103 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score	0.01 score on a scale Standard Error 0.03	0.06 score on a scale Standard Error 0.03	0.01 score on a scale Standard Error 0.03

SECONDARY outcome

Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP.

The UKU rating scale is a semi-structured interview used to assess the side effects of participants being treated with antipsychotic drugs. The scale is divided into 6 sub-scales: Psychic, neurological, autonomic, other, global assessment by subject, and global assessment by doctor. The scale has a total of 48 items, each item is rated on a 4-point scale (0=not present; 1=mild; 2=moderate; 3=severe), and the total score ranges from 0 to 144. Higher ratings indicate greater impairment. The severe side effects are reported in this outcome measure.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=102 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=104 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Psychic: Concentration Difficulties	7 Participants	10 Participants	8 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Psychic: Asthenia/Lassitude	6 Participants	3 Participants	1 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Psychic: Failing Memory	2 Participants	2 Participants	4 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Psychic: Depression	0 Participants	2 Participants	1 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Psychic: Tension/Inner Unrest	4 Participants	3 Participants	9 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Psychic: Increased Duration of Sleep	0 Participants	1 Participants	0 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Psychic: Reduced Duration of Sleep	4 Participants	1 Participants	1 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Psychic: Increased Dream Activity	0 Participants	2 Participants	0 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Psychic: Emotional Indifference	3 Participants	6 Participants	6 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Neurologic: Akathisia	1 Participants	1 Participants	0 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Autonomic: Nausea/Vomiting	0 Participants	0 Participants	1 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Autonomic: Micturition Disturbances	0 Participants	1 Participants	0 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Autonomic: Palpitations/Tachycardia	1 Participants	0 Participants	1 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Autonomic: Increased Tendency to Sweating	1 Participants	0 Participants	0 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Other: Weight Gain	0 Participants	1 Participants	0 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Other: Amenorrhoea	0 Participants	1 Participants	0 Participants
Number of Participants With Severe Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale Other: Migraine	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to last dose of study drug (up to approximately 6 weeks)

Population: Safety sample included all randomized participants who received at least 1 dose of IMP.

The NY-AACENT is used to detect changes in cognitive function subsequent to pharmacological or similar treatments for neurological or psychiatric problems, specifically designed to be used in pediatric population (ages 12 to 17), but could have been utilized with other age groups, as appropriate. Number of participants with at least one occurrence of the corresponding signs/symptoms are reported in this outcome measure.

Outcome measures

Measure	Brexpiprazole n=110 Participants Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=102 Participants Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=104 Participants Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Number of Participants With Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) Working Memory	88 Participants	79 Participants	83 Participants
Number of Participants With Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) Attention/Vigilance	98 Participants	90 Participants	91 Participants
Number of Participants With Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) Verbal Learning	71 Participants	70 Participants	69 Participants
Number of Participants With Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) Visual Learning	46 Participants	46 Participants	44 Participants
Number of Participants With Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) Reasoning	97 Participants	86 Participants	83 Participants
Number of Participants With Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) Speed of Processing	88 Participants	84 Participants	82 Participants
Number of Participants With Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) Social Cognition	91 Participants	87 Participants	84 Participants
Number of Participants With Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) Any Signs/Symptoms	100 Participants	91 Participants	92 Participants

Adverse Events

Brexpiprazole

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Aripiprazole

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Brexpiprazole n=110 participants at risk Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=102 participants at risk Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=104 participants at risk Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Psychiatric disorders Psychotic Disorder	0.00% 0/110 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	0.98% 1/102 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	0.96% 1/104 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.
Psychiatric disorders Schizophrenia	0.91% 1/110 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	0.00% 0/102 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	1.9% 2/104 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.

Other adverse events

Measure	Brexpiprazole n=110 participants at risk Participants were administered with brexpiprazole oral tablets, daily, dose titrated up to 0.5 mg by Day 4, 1 mg by Day 7, 2 mg by Day 14, then between 2-4 mg after Day 21 up to Week 6 with a 1 mg increase or decrease, based on the Investigator's decision.	Aripiprazole n=102 participants at risk Participants were administered with aripiprazole oral tablets, daily, dose titrated up to 2 mg by Day 4, 5 mg by Day 7, 10 mg by Day 14, then 10, 15 or 20 mg after Day 21 up to Week 6 with a 5 mg increase or decrease, based on the Investigator's decision.	Placebo n=104 participants at risk Participants were administered with brexpiprazole or aripiprazole matching placebo oral tablets, daily up to Week 6.
Gastrointestinal disorders Nausea	6.4% 7/110 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	3.9% 4/102 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	3.8% 4/104 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.
General disorders Fatigue	1.8% 2/110 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	7.8% 8/102 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	0.00% 0/104 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.
Nervous system disorders Akathisia	3.6% 4/110 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	6.9% 7/102 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	2.9% 3/104 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.
Nervous system disorders Headache	6.4% 7/110 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	4.9% 5/102 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	4.8% 5/104 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.
Nervous system disorders Somnolence	4.5% 5/110 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	10.8% 11/102 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 dose of IMP.	4.8% 5/104 • From the first dose of study drug up to 21 days after the last dose of study drug (up to approximately 9 weeks) Safety sample included all randomized participants who received at least 1 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