(Cmax) Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.

PK parameter - CL/F was assessed for brexpiprazole only. Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.

Tmax for brexpiprazole and its metabolite DM-3411. Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.

The AIMS Scale was an extrapyramidal symptoms (EPS) rating scale. The AIMS is a 12 item scale. The first 10 items e.g. facial and oral movements (items 1-4), extremity movements (items 5 and 6), trunk movements (item 7), investigators global assessment of dyskinesia (items 8 to 10). The first 10 items are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28, with a higher score indicating worse outcome. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The SAS is a rating scale used to measure EPS. The SAS scale 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), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40, with higher scores indicating worse outcome. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The BARS consisted of 4 items related to akathisia: objective observation of akathisia by the study physician, subjective feelings of restlessness by the participant, participant distress due to akathisia, and global evaluation of akathisia. The first 3 items were rated on a 4-point scale, with a score of 0 = absence of symptoms and a score of 3 = severe condition. The global clinical evaluation were made on a 6-point scale, (0=absent, 1=questionable, 2=mild, 3=moderate, 4=marked, 5=severe). To complete this scale, participants were observed while they were seated and then stood for a minimum of 2 minutes in each position. Symptoms observed in other situations (e.g., while engaged in neutral conversation or engaged in activity on the ward) may also be rated. Subjective phenomena were to be elicited by direct questioning. The BARS total score (when combined) ranged from 0 to 18, with higher values indicating a severe condition.

The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Suicidality was defined as reporting at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any type of suicidal behaviors (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). The suicidal ideation intensity 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) which leads to the range of the total score from 0 to 25, with a higher score indicating a worse outcome. A missing score of any item resulted in a missing total score. If no suicidal ideation was reported, a score of 0 was given to the intensity scale. Last Visit is last scheduled post-baseline evaluation including early termination evaluation.

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) and a score of 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 ranged from 30 (best possible outcome) to 210 (worst possible outcome). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

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) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

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) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at baseline. Response choices include: 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. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.

Total of all reporting groups

Participants received 1-mg brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.

Mean (±SD) Serotonin 5-HT1A Receptor Occupancy Using the Radiotracer [11C]CUMI101 in high dose only. In cohorts 1, 2 and 3, the binding of brexpiprazole to the 5-HT1A receptors was assessed by comparing the binding potential from the Baseline scan (prior to treatment) to that of Day 10 (after treatment). The 5-HT1A receptors following administration of a 4-mg dose of brexpiprazole was assessed and the occupancy estimates were averaged across brain regions 4 hours post-last dose on Day 10.

The PET analysis included all participants who had both the Baseline and Day 10 PET scans performed.

Mean (±SD) Serotonin 5-HT2A Receptor Occupancy Using the Radiotracer [11C]MDL100907 (in low and high dose). The 5-HT2A receptors following administration of 1- and 4-mg doses of brexpiprazole were assessed and the occupancy estimates were averaged across brain regions 4 hours post-last dose on Day 10.

The PET analysis included all participants who had both the Baseline and Day 10 PET scans performed.

Mean (±SD) SERT Occupancy Using the Radiotracer [11C]DASB in high dose only. Occupancy estimates were averaged across brain regions 4 hours post-last dose.

The PET analysis included all participants who had both the Baseline and Day 10 PET scans performed.

AUC during a dosing interval at steady-state for brexpiprazole and its metabolite DM-3411. Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.

The PK analysis included participants who had valid measurements (per clinical pharmacology). Blood samples were collected on Days 1 and 9 at predose and Day 10 at predose and at 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-last dose or at early termination (ET).

(Cmax) Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.

The PK analysis included participants who had valid measurements (per clinical pharmacology). Blood samples were collected on Days 1 and 9 at predose and Day 10 at predose and at 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-last dose or at ET.

PK parameter - CL/F was assessed for brexpiprazole only. Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.

The PK analysis included participants who had valid measurements (per clinical pharmacology). Blood samples were collected on Days 1 and 9 at predose and Day 10 at predose and at 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-last dose or at ET.

Tmax for brexpiprazole and its metabolite DM-3411. Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.

The PK analysis included participants who had valid measurements (per clinical pharmacology). Blood samples were collected on Days 1 and 9 at predose and Day 10 at predose and at 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-last dose or at ET.

The AIMS Scale was an extrapyramidal symptoms (EPS) rating scale. The AIMS is a 12 item scale. The first 10 items e.g. facial and oral movements (items 1-4), extremity movements (items 5 and 6), trunk movements (item 7), investigators global assessment of dyskinesia (items 8 to 10). The first 10 items are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28, with a higher score indicating worse outcome. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The safety population included all participants who received at least one dose of study medication.

The SAS is a rating scale used to measure EPS. The SAS scale 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), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40, with higher scores indicating worse outcome. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The safety population included all participants who received at least one dose of study medication.

The BARS consisted of 4 items related to akathisia: objective observation of akathisia by the study physician, subjective feelings of restlessness by the participant, participant distress due to akathisia, and global evaluation of akathisia. The first 3 items were rated on a 4-point scale, with a score of 0 = absence of symptoms and a score of 3 = severe condition. The global clinical evaluation were made on a 6-point scale, (0=absent, 1=questionable, 2=mild, 3=moderate, 4=marked, 5=severe). To complete this scale, participants were observed while they were seated and then stood for a minimum of 2 minutes in each position. Symptoms observed in other situations (e.g., while engaged in neutral conversation or engaged in activity on the ward) may also be rated. Subjective phenomena were to be elicited by direct questioning. The BARS total score (when combined) ranged from 0 to 18, with higher values indicating a severe condition.

The safety population included all participants who received at least one dose of study medication.

The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Suicidality was defined as reporting at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any type of suicidal behaviors (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). The suicidal ideation intensity 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) which leads to the range of the total score from 0 to 25, with a higher score indicating a worse outcome. A missing score of any item resulted in a missing total score. If no suicidal ideation was reported, a score of 0 was given to the intensity scale. Last Visit is last scheduled post-baseline evaluation including early termination evaluation.

The safety population included all participants who received at least one dose of study medication.

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) and a score of 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 ranged from 30 (best possible outcome) to 210 (worst possible outcome). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The safety sample included participants that are administered at least one dose of study medication.

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) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The safety population included all participants who received at least one dose of study medication.

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) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The safety population included all participants who received at least one dose of study medication.

The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The safety population included all participants who received at least one dose of study medication.

The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at baseline. Response choices include: 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. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.

The safety population included all participants who received at least one dose of study medication.

Participants in cohort 2 received one 1-mg tablet of brexpiprazole once daily on Days 1 to 10.

Participants in cohort 3 received once 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and one 4-mg tablet of brexpiprazole once daily on Days 4 to 10.