Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults With Schizophrenia (NCT NCT01668797)

Results Overview

The primary efficacy variable was time to impending relapse from randomization, as assessed by Clinical Global Impression of Improvement (CGI-I) score ≥5, Positive and Negative Syndrome Scale (PANSS) scores for hostility or uncooperativeness ≥5, or ≥20% increase in PANSS Total Score. Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score \>4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content).OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of "yes" to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.The measure type, number is Hazard Ratio.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

524 participants

Primary outcome timeframe

From randomization to time of exacerbation of psychotic symptoms/impending relapse - up to 52 weeks

Results posted on

2017-01-13

Participant Flow

A total of 753 participants were screened at 49 trial sites in the following 7 countries: United States (US, including Puerto Rico), Malaysia, Colombia, Romania, Ukraine, Serbia, and Turkey.

Trial had Phase A (Conversion) (N= 406), Phase B (Oral Stabilization) (N= 464; 346 rolled over from Phase A and 118 entered directly into Phase B ) and Phase C (Double-Blind Maintenance) with (N= 202 rolled over from Phase B). Participants were randomized in to Phase C in a 1:1 ratio (brexpiprazole:placebo) to receive treatment for up to 52 weeks.

Participant milestones

Participant milestones
Measure	Phase A (Conversion Phase) The purpose of the open-label conversion phase was 2-fold: 1) to cross-titrate the participants current antipsychotic treatment to brexpiprazole monotherapy over a period of 1 to 4 weeks and 2) to allow washout of prohibited medications in preparation for the stabilization phase.	Phase B (Stabilization Phase) This single-blind stabilization phase was to titrate participants to a dose of brexpiprazole (1 to 4 mg/day) that would maintain stability of psychotic symptoms over 12 consecutive weeks (within a maximum of 36 weeks), while minimizing tolerability issues.	Phase C - Brexpiprazole (Double-Blind Maintenance Phase) Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Phase C - Placebo (Double-Blind Maintenance Phase) Participants received placebo orally once daily for 52 weeks.
Phase A (Conversion Phase) STARTED	406	0	0	0
Phase A (Conversion Phase) COMPLETED	346	0	0	0
Phase A (Conversion Phase) NOT COMPLETED	60	0	0	0
Phase B (Stabilization Phase) STARTED	0	464	0	0
Phase B (Stabilization Phase) COMPLETED	0	202	0	0
Phase B (Stabilization Phase) NOT COMPLETED	0	262	0	0
Phase C (Double-Blind Maintenance Phase) STARTED	0	0	97	105
Phase C (Double-Blind Maintenance Phase) COMPLETED	0	0	14	9
Phase C (Double-Blind Maintenance Phase) NOT COMPLETED	0	0	83	96

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase A (Conversion Phase) The purpose of the open-label conversion phase was 2-fold: 1) to cross-titrate the participants current antipsychotic treatment to brexpiprazole monotherapy over a period of 1 to 4 weeks and 2) to allow washout of prohibited medications in preparation for the stabilization phase.	Phase B (Stabilization Phase) This single-blind stabilization phase was to titrate participants to a dose of brexpiprazole (1 to 4 mg/day) that would maintain stability of psychotic symptoms over 12 consecutive weeks (within a maximum of 36 weeks), while minimizing tolerability issues.	Phase C - Brexpiprazole (Double-Blind Maintenance Phase) Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Phase C - Placebo (Double-Blind Maintenance Phase) Participants received placebo orally once daily for 52 weeks.
Phase A (Conversion Phase) Lost to Follow-up	3	0	0	0
Phase A (Conversion Phase) Met Withdrawal Criteria	3	0	0	0
Phase A (Conversion Phase) Physician Decision	2	0	0	0
Phase A (Conversion Phase) Withdrawal by Subject	16	0	0	0
Phase A (Conversion Phase) Protocol Violation	2	0	0	0
Phase A (Conversion Phase) Lack of Efficacy	7	0	0	0
Phase A (Conversion Phase) Adverse Event Without Impending Relapse	8	0	0	0
Phase A (Conversion Phase) Terminated Study on Interim Analysis	19	0	0	0
Phase B (Stabilization Phase) Lost to Follow-up	0	16	0	0
Phase B (Stabilization Phase) Met Withdrawal Criteria	0	22	0	0
Phase B (Stabilization Phase) Physician Decision	0	11	0	0
Phase B (Stabilization Phase) Withdrawal by Subject	0	60	0	0
Phase B (Stabilization Phase) Protocol Violation	0	3	0	0
Phase B (Stabilization Phase) Lack of Efficacy	0	21	0	0
Phase B (Stabilization Phase) Adverse Event Without Impending Relapse	0	43	0	0
Phase B (Stabilization Phase) Terminated Study on Interim Analysis	0	86	0	0
Phase C (Double-Blind Maintenance Phase) Lost to Follow-up	0	0	4	6
Phase C (Double-Blind Maintenance Phase) Met Withdrawal Criteria	0	0	3	3
Phase C (Double-Blind Maintenance Phase) Physician Decision	0	0	5	2
Phase C (Double-Blind Maintenance Phase) Withdrawal by Subject	0	0	3	5
Phase C (Double-Blind Maintenance Phase) Protocol Violation	0	0	2	0
Phase C (Double-Blind Maintenance Phase) Lack of Efficacy	0	0	2	10
Phase C (Double-Blind Maintenance Phase) Lack of Efficacy without AE	0	0	11	30
Phase C (Double-Blind Maintenance Phase) Adverse Event Without Impending Relapse	0	0	4	2
Phase C (Double-Blind Maintenance Phase) Terminated Study on Interim Analysis	0	0	49	38

Baseline Characteristics

Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults With Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase C - Brexpiprazole (Double-Blind Maintenance Phase) n=97 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Phase C - Placebo (Double-Blind Maintenance Phase) n=105 Participants Participants received placebo orally once daily for 52 weeks.	Total n=202 Participants Total of all reporting groups
Age, Continuous	38.8 years STANDARD_DEVIATION 10.7 • n=5 Participants	41.6 years STANDARD_DEVIATION 10.6 • n=7 Participants	40.2 years STANDARD_DEVIATION 10.7 • n=5 Participants
Gender Female	39 Participants n=5 Participants	40 Participants n=7 Participants	79 Participants n=5 Participants
Gender Male	58 Participants n=5 Participants	65 Participants n=7 Participants	123 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to time of exacerbation of psychotic symptoms/impending relapse - up to 52 weeks

Population: Based on the Intent-to-Treat (ITT) principle, the full analysis set of this trial was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

The primary efficacy variable was time to impending relapse from randomization, as assessed by Clinical Global Impression of Improvement (CGI-I) score ≥5, Positive and Negative Syndrome Scale (PANSS) scores for hostility or uncooperativeness ≥5, or ≥20% increase in PANSS Total Score. Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score \>4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content).OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of "yes" to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.The measure type, number is Hazard Ratio.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.	0.292 Days Interval 0.156 to 0.548	3.420 Days Interval 1.825 to 6.411

SECONDARY outcome

Timeframe: Baseline and Week 52/Early Termination

Population: Based on ITT principle, the full analysis set of this trial was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score \> 4 with an absolute increase of ≥ 2 on that specific item or an increase on any of the following individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual though content) to a score of \>4 and an absolute increase of ≥ 4 on the combined 4 PANSS items. OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Current suicidal behavior as assessed by the C-SSRS (ie, an answer of "yes" to any of the questions on the suicidal behavior section of the C-SSRS 5) Violent or aggressive behavior resulting in clinically significant self-injury to another person, or property damage.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance Phase	13.54 percentage of participants	38.46 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 6, 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set of this trial was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

Participants were assessed for stability using the following criteria:1) Outpatient status AND 2) Positive and Negative Syndrome Scale (PANSS) Total Score ≤ 70 AND 3) A score of ≤ 4 (moderate) on each of the following PANSS items (possible scores of 1 to 7 for each item): conceptual disorganization, suspiciousness hallucinatory behavior, unusual thought content, AND 4) Clinical Global Impression - Severity of Illness scale(CGI-S) score ≤ 4 (moderately ill) AND 5) No current suicidal behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS), defined as the following: An answer of "no" to each question on the Suicidal Behavior section of the C-SSRS AND an answer of "no" to Questions 4 and 5 on the Suicidal Ideation section of the C-SSRS, if completed, AND 6) No evidence of aggressive or violent behavior resulting in clinically significant self-injury, injury to another person, property damage.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase Week 6 (N= 81, 84)	92.59 percentage of participants	86.90 percentage of participants
Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase Week 12 (N= 73, 68)	93.15 percentage of participants	86.76 percentage of participants
Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase Week 24 (N= 50, 36)	96.00 percentage of participants	94.44 percentage of participants
Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase Week 36 (N= 33, 24)	93.94 percentage of participants	83.33 percentage of participants
Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase Week 52 (N= 15, 9)	86.67 percentage of participants	88.89 percentage of participants
Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase Last Visit (N= 96, 104)	79.17 percentage of participants	56.73 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

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).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis Week 6 (N= 81, 84)	0.79 Units on a scale Standard Error 1.31	4.09 Units on a scale Standard Error 1.27
Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis Week 12 (N= 73, 68)	0.84 Units on a scale Standard Error 1.73	6.15 Units on a scale Standard Error 1.74
Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis Week 36 (N= 33, 24)	-2.71 Units on a scale Standard Error 1.48	3.33 Units on a scale Standard Error 1.70
Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis Week 24 (N= 50, 36)	-1.88 Units on a scale Standard Error 1.39	2.89 Units on a scale Standard Error 1.55
Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis Week 52 (N= 15, 9)	0.61 Units on a scale Standard Error 3.34	6.92 Units on a scale Standard Error 4.53

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

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).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis Week 24	1.58 Units on a scale Standard Error 1.88	9.17 Units on a scale Standard Error 1.72
Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis Week 6	0.51 Units on a scale Standard Error 1.40	3.56 Units on a scale Standard Error 1.28
Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis Week 12	1.55 Units on a scale Standard Error 1.77	6.60 Units on a scale Standard Error 1.62
Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis Week 36	2.49 Units on a scale Standard Error 1.89	10.51 Units on a scale Standard Error 1.73
Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis Week 52	3.25 Units on a scale Standard Error 1.94	11.20 Units on a scale Standard Error 1.77

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

PANSS consisted of three subscales: a total of 30 symptom constructs. For each 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 score ranged from 7 (best possible outcome) to 49 (worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis Week 24 (N= 50, 36)	-0.84 Units on a scale Standard Error 0.46	0.72 Units on a scale Standard Error 0.51
Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis Week 6 (N= 81, 84)	0.17 Units on a scale Standard Error 0.42	1.28 Units on a scale Standard Error 0.41
Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis Week 12 (N= 73, 68)	-0.06 Units on a scale Standard Error 0.50	1.81 Units on a scale Standard Error 0.51
Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis Week 36 (N= 33, 24)	-0.97 Units on a scale Standard Error 0.44	0.91 Units on a scale Standard Error 0.51
Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis Week 52 (N= 15, 9)	-1.21 Units on a scale Standard Error 0.73	1.50 Units on a scale Standard Error 0.99

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

PANSS consisted of three subscales: a total of 30 symptom constructs. For each 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 score ranged from 7 (best possible outcome) to 49 (worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis Week 6	0.30 Units on a scale Standard Error 0.49	1.25 Units on a scale Standard Error 0.45
Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis Week 12	0.38 Units on a scale Standard Error 0.59	2.24 Units on a scale Standard Error 0.54
Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis Week 24	0.49 Units on a scale Standard Error 0.64	3.23 Units on a scale Standard Error 0.59
Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis Week 36	0.97 Units on a scale Standard Error 0.63	3.91 Units on a scale Standard Error 0.58
Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis Week 52	0.99 Units on a scale Standard Error 0.64	4.17 Units on a scale Standard Error 0.59

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

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 score ranged from 7 (best possible outcome) to 49 (worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis Week 6 (N= 81, 84)	-0.04 Units on a scale Standard Error 0.37	0.65 Units on a scale Standard Error 0.35
Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis Week 12 (N= 73, 68)	-0.22 Units on a scale Standard Error 0.43	0.55 Units on a scale Standard Error 0.44
Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis Week 24 (N= 50, 36)	-0.78 Units on a scale Standard Error 0.39	0.18 Units on a scale Standard Error 0.42
Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis Week 36 (N= 33, 24)	-1.03 Units on a scale Standard Error 0.47	0.02 Units on a scale Standard Error 0.53
Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis Week 52 (N= 15, 9)	1.30 Units on a scale Standard Error 1.37	0.87 Units on a scale Standard Error 1.71

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

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 score ranged from 7 (best possible outcome) to 49 (worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis Week 36	-0.14 Units on a scale Standard Error 0.51	1.44 Units on a scale Standard Error 0.46
Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis Week 24	-0.08 Units on a scale Standard Error 0.49	1.47 Units on a scale Standard Error 0.44
Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis Week 52	0.39 Units on a scale Standard Error 0.54	1.63 Units on a scale Standard Error 0.49
Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis Week 6	-0.12 Units on a scale Standard Error 0.39	0.63 Units on a scale Standard Error 0.35
Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis Week 12	-0.17 Units on a scale Standard Error 0.46	1.06 Units on a scale Standard Error 0.42

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Weeks 6, 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

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.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis Week 36 (N= 33, 24)	-0.31 Units on a scale Standard Error 0.11	0.25 Units on a scale Standard Error 0.12
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis Week 24 (N= 50, 36)	-0.16 Units on a scale Standard Error 0.10	0.21 Units on a scale Standard Error 0.10
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis Week 52 (N= 15, 9)	-0.23 Units on a scale Standard Error 0.17	0.28 Units on a scale Standard Error 0.22
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis Week 6 (N= 81, 84)	-0.01 Units on a scale Standard Error 0.09	0.26 Units on a scale Standard Error 0.09
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis Week 12 (N= 73, 68)	-0.01 Units on a scale Standard Error 0.11	0.37 Units on a scale Standard Error 0.11

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

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.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis Week 36	-0.00 Units on a scale Standard Error 0.11	0.56 Units on a scale Standard Error 0.10
Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis Week 52	0.02 Units on a scale Standard Error 0.11	0.55 Units on a scale Standard Error 0.11
Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis Week 6	-0.08 Units on a scale Standard Error 0.09	0.17 Units on a scale Standard Error 0.09
Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis Week 12	-0.04 Units on a scale Standard Error 0.11	0.32 Units on a scale Standard Error 0.10
Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis Week 24	-0.03 Units on a scale Standard Error 0.11	0.47 Units on a scale Standard Error 0.10

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

The rater or investigator would rate the participant's total improvement whether or not it is due entirely to study treatment. During Phase B, responses were compared to the participant's condition at Baseline of Phase B (for participants who entered Phase B directly after screening) or to the End of Phase A visit (for participants who participated in Phase A). During Phase C, responses were compared to the participant's condition at the End of Phase B visit. 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.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis Week 6	3.68 Units on a scale Standard Deviation 0.98	4.00 Units on a scale Standard Deviation 1.14
Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis Week 12	3.66 Units on a scale Standard Deviation 1.19	4.10 Units on a scale Standard Deviation 1.30
Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis Week 52	3.77 Units on a scale Standard Deviation 1.26	4.40 Units on a scale Standard Deviation 1.32
Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis Week 24	3.67 Units on a scale Standard Deviation 1.27	4.30 Units on a scale Standard Deviation 1.32
Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis Week 36	3.71 Units on a scale Standard Deviation 1.27	4.39 Units on a scale Standard Deviation 1.30

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 24 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

The PSP is a validated clinician-rated scale that measures personal and social functioning in four domains: socially useful activities (e.g., work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment in each of these domains is rated as absent, mild, manifest, marked, severe, or very severe. These ratings are then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment to determine the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 are considered to have mild functional difficulty. Scores of 31 to 70 represent manifest disabilities of various degrees and ratings of 1 to 30 indicate minimal functioning that requires intense support and/or supervision.The PSP score ranges from 0 to 100, with higher scores indicating higher levels of social functioning.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in Personal and Social Performance (PSP) Scale Score - MMRM Analysis Week 24 (N= 50, 36)	18.85 Units on a scale Standard Error 1.51	17.84 Units on a scale Standard Error 1.82
Mean Change From Baseline in Personal and Social Performance (PSP) Scale Score - MMRM Analysis Week 52 (N= 15, 9)	18.63 Units on a scale Standard Error 2.76	12.55 Units on a scale Standard Error 3.48

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 24 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

The PSP is a validated clinician-rated scale that measures personal and social functioning in four domains: socially useful activities (e.g., work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment in each of these domains is rated as absent, mild, manifest, marked, severe, or very severe. These ratings are then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment to determine the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 are considered to have mild functional difficulty. Scores of 31 to 70 represent manifest disabilities of various degrees and ratings of 1 to 30 indicate minimal functioning that requires intense support and/or supervision.The PSP score ranges from 0 to 100, with higher scores indicating higher levels of social functioning.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=94 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=100 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PSP Scale Score - LOCF Analysis Week 24	15.20 Units on a scale Standard Error 1.41	11.41 Units on a scale Standard Error 1.32
Mean Change From Baseline in PSP Scale Score - LOCF Analysis Week 52	15.06 Units on a scale Standard Error 1.43	10.31 Units on a scale Standard Error 1.34

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

The GAF is a clinician-rated scale that assesses the participant's psychological, social, and occupational functioning on a hypothetical continuum of mental health-illness using a scale that ranges from 1 to 100 score, where lower values indicate worst outcome. From among 10 descriptive anchors, investigators will choose the anchor which is the most representative of the participant's level of functioning at the time of the assessment and will assign a single score within the point range given for the selected anchor.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis Week 12 (N= 73, 68)	1.59 Units on a scale Standard Error 1.27	-0.03 Units on a scale Standard Error 1.29
Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis Week 24 (N= 50, 36)	3.74 Units on a scale Standard Error 1.42	1.09 Units on a scale Standard Error 1.57
Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis Week 36 (N= 33, 24)	4.71 Units on a scale Standard Error 1.50	0.21 Units on a scale Standard Error 1.67
Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis Week 52 (N= 15, 9)	5.72 Units on a scale Standard Error 1.87	-0.16 Units on a scale Standard Error 2.37

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

The GAF is a clinician-rated scale that assesses the participant's psychological, social, and occupational functioning on a hypothetical continuum of mental health-illness using a scale that ranges from 1 to 100 score, where lower values indicate worst outcome. From among 10 descriptive anchors, investigators will choose the anchor which is the most representative of the participant's level of functioning at the time of the assessment and will assign a single score within the point range given for the selected anchor.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=95 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=102 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in GAF Scale Score - LOCF Analysis Week 12	0.44 Units on a scale Standard Error 1.26	-3.44 Units on a scale Standard Error 1.17
Mean Change From Baseline in GAF Scale Score - LOCF Analysis Week 24	0.85 Units on a scale Standard Error 1.37	-4.51 Units on a scale Standard Error 1.27
Mean Change From Baseline in GAF Scale Score - LOCF Analysis Week 36	0.97 Units on a scale Standard Error 1.35	-5.84 Units on a scale Standard Error 1.25
Mean Change From Baseline in GAF Scale Score - LOCF Analysis Week 52	0.55 Units on a scale Standard Error 1.38	-6.01 Units on a scale Standard Error 1.28

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

Analysis of the percentage of participants who discontinued due to all causes was based on all participants who have been randomized and taken one dose of IMP in the Double-blind Maintenance phase. The trial was completed by sponsor when efficacy was demonstrated at the first pre-specified interim analysis (45 impending relapse events) performed by an independent (unblinded) statistician.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Percentage of Participants Who Discontinued Due to All Causes	34.38 Percentage of particpants	54.81 Percentage of particpants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The last-observation-carried-forward (LOCF) data set included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data (eg.the last visit prior to the first dosing of Phase C) were not be carried forward to impute missing values for the LOCF data set.

The PEC score consisted of five PANSS items: excitement (P4), hostility (P7), tension (G4), uncooperativeness (G8), and poor impulse control (G14). Each of the items were rated on a scale of 1 (absent) to 7 (extreme). The PEC scores ranged from 5 (not present) to 35 (extremely severe).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis Week 6 (N= 81, 84)	0.32 Units on a scale Standard Error 0.23	0.74 Units on a scale Standard Error 0.22
Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis Week 12 (N= 73, 68)	0.50 Units on a scale Standard Error 0.34	1.16 Units on a scale Standard Error 0.35
Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis Week 24 (N= 50, 36)	-0.06 Units on a scale Standard Error 0.31	0.45 Units on a scale Standard Error 0.36
Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis Week 36 (N= 33, 24)	0.10 Units on a scale Standard Error 0.33	1.25 Units on a scale Standard Error 0.40
Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis Week 52 (N= 15, 9)	-0.04 Units on a scale Standard Error 0.46	1.00 Units on a scale Standard Error 0.59

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

The PEC score consisted of five PANSS items: excitement (P4), hostility (P7), tension (G4), uncooperativeness (G8), and poor impulse control (G14). Each of the items were rated on a scale of 1 (absent) to 7 (extreme). The PEC scores ranged from 5 (not present) to 35 (extremely severe).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PEC Score - LOCF Analysis Week 24	0.78 Units on a scale Standard Error 0.42	1.86 Units on a scale Standard Error 0.38
Mean Change From Baseline in PEC Score - LOCF Analysis Week 36	0.89 Units on a scale Standard Error 0.41	2.23 Units on a scale Standard Error 0.38
Mean Change From Baseline in PEC Score - LOCF Analysis Week 52	0.82 Units on a scale Standard Error 0.41	2.35 Units on a scale Standard Error 0.38
Mean Change From Baseline in PEC Score - LOCF Analysis Week 6	0.38 Units on a scale Standard Error 0.27	0.81 Units on a scale Standard Error 0.25
Mean Change From Baseline in PEC Score - LOCF Analysis Week 12	0.73 Units on a scale Standard Error 0.36	1.36 Units on a scale Standard Error 0.33

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis Week 6 (N= 81, 84)	-0.10 Units on a scale Standard Error 0.45	1.24 Units on a scale Standard Error 0.44
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis Week 12 (N= 73, 68)	-0.18 Units on a scale Standard Error 0.58	1.83 Units on a scale Standard Error 0.58
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis Week 24 (N= 50, 36)	-0.82 Units on a scale Standard Error 0.54	0.77 Units on a scale Standard Error 0.60
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis Week 36 (N= 33, 24)	-1.35 Units on a scale Standard Error 0.57	0.93 Units on a scale Standard Error 0.63
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis Week 52 (N= 15, 9)	-1.62 Units on a scale Standard Error 0.83	1.78 Units on a scale Standard Error 1.05

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis Week 6	0.05 Units on a scale Standard Error 0.50	1.13 Units on a scale Standard Error 0.46
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis Week 12	0.10 Units on a scale Standard Error 0.61	2.03 Units on a scale Standard Error 0.56
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis Week 24	0.25 Units on a scale Standard Error 0.66	3.08 Units on a scale Standard Error 0.61
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis Week 36	0.60 Units on a scale Standard Error 0.66	3.69 Units on a scale Standard Error 0.60
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis Week 52	0.58 Units on a scale Standard Error 0.66	4.02 Units on a scale Standard Error 0.60

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis Week 12 (N= 73, 68)	-0.01 Units on a scale Standard Error 0.45	0.80 Units on a scale Standard Error 0.45
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis Week 24 (N= 50, 36)	-0.71 Units on a scale Standard Error 0.40	0.46 Units on a scale Standard Error 0.43
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis Week 36 (N= 33, 24)	-0.80 Units on a scale Standard Error 0.50	0.70 Units on a scale Standard Error 0.56
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis Week 52 (N= 15, 9)	1.37 Units on a scale Standard Error 1.39	1.06 Units on a scale Standard Error 1.77
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis Week 6 (N= 81, 84)	0.02 Units on a scale Standard Error 0.38	0.68 Units on a scale Standard Error 0.36

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis Week 6	-0.24 Units on a scale Standard Error 0.40	0.61 Units on a scale Standard Error 0.36
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis Week 12	-0.15 Units on a scale Standard Error 0.48	1.09 Units on a scale Standard Error 0.43
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis Week 24	-0.09 Units on a scale Standard Error 0.49	1.50 Units on a scale Standard Error 0.44
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis Week 36	-0.07 Units on a scale Standard Error 0.52	1.56 Units on a scale Standard Error 0.47
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis Week 52	0.34 Units on a scale Standard Error 0.56	1.57 Units on a scale Standard Error 0.50

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis Week 6 (N= 81, 84)	-0.18 Units on a scale Standard Error 0.31	0.32 Units on a scale Standard Error 0.30
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis Week 12 (N= 73, 68)	-0.44 Units on a scale Standard Error 0.38	0.69 Units on a scale Standard Error 0.39
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis Week 24 (N= 50, 36)	-1.26 Units on a scale Standard Error 0.34	0.27 Units on a scale Standard Error 0.38
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis Week 36 (N= 33, 24)	-1.31 Units on a scale Standard Error 0.44	0.17 Units on a scale Standard Error 0.50
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis Week 52 (N= 15, 9)	-0.37 Units on a scale Standard Error 0.99	-0.30 Units on a scale Standard Error 1.24

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis Week 6	-0.32 Units on a scale Standard Error 0.34	0.33 Units on a scale Standard Error 0.31
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis Week 12	-0.19 Units on a scale Standard Error 0.41	1.19 Units on a scale Standard Error 0.38
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis Week 24	-0.29 Units on a scale Standard Error 0.44	1.76 Units on a scale Standard Error 0.41
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis Week 36	0.00 Units on a scale Standard Error 0.45	1.95 Units on a scale Standard Error 0.42
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis Week 52	0.29 Units on a scale Standard Error 0.48	1.97 Units on a scale Standard Error 0.45

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis Week 6 (N= 81, 84)	0.19 Units on a scale Standard Error 0.19	0.55 Units on a scale Standard Error 0.18
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis Week 12 (N= 73, 68)	0.33 Units on a scale Standard Error 0.28	0.82 Units on a scale Standard Error 0.29
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis Week 24 (N= 50, 36)	-0.26 Units on a scale Standard Error 0.27	0.81 Units on a scale Standard Error 0.31
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis Week 36 (N= 33, 24)	-0.13 Units on a scale Standard Error 0.29	0.94 Units on a scale Standard Error 0.34
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis Week 52 (N= 15, 9)	-0.20 Units on a scale Standard Error 0.40	0.94 Units on a scale Standard Error 0.50

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis Week 6	0.32 Units on a scale Standard Error 0.22	0.65 Units on a scale Standard Error 0.21
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis Week 12	0.52 Units on a scale Standard Error 0.30	0.94 Units on a scale Standard Error 0.28
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis Week 24	0.50 Units on a scale Standard Error 0.36	1.31 Units on a scale Standard Error 0.33
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis Week 36	0.57 Units on a scale Standard Error 0.36	1.63 Units on a scale Standard Error 0.33
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis Week 52	0.49 Units on a scale Standard Error 0.37	1.75 Units on a scale Standard Error 0.34

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: Based on ITT principle, the full analysis set was composed of all participants randomized to the double-blind treatment who took at least one dose of study medication in Phase C and who had at least one post-randomization efficacy evaluation in Phase C.

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The anxiety/depression factor score is the sum of score from the 4 items on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis Week 6 (N= 81, 84)	0.19 Units on a scale Standard Error 0.25	0.66 Units on a scale Standard Error 0.24
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis Week 12 (N= 73, 68)	0.54 Units on a scale Standard Error 0.29	0.78 Units on a scale Standard Error 0.29
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis Week 24 (N= 50, 36)	0.61 Units on a scale Standard Error 0.28	0.58 Units on a scale Standard Error 0.32
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis Week 36 (N= 33, 24)	0.46 Units on a scale Standard Error 0.33	0.71 Units on a scale Standard Error 0.39
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis Week 52 (N= 15, 9)	0.04 Units on a scale Standard Error 0.43	0.28 Units on a scale Standard Error 0.56

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Weeks 6, 12, 24, 36 and 52

Population: The LOCF data set for Phase C included data recorded at a given Phase C visit or, if no observation is recorded at that visit, data carried forward from the previous Phase C visit. Baseline data was not be carried forward to impute missing values for the LOCF data set.

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The anxiety/depression factor score is the sum of score from the 4 items on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome).

Outcome measures

Outcome measures
Measure	Brexpiprazole n=96 Participants Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo n=104 Participants Participants received placebo orally once daily for 52 weeks.
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis Week 6	0.19 Units on a scale Standard Error 0.27	0.85 Units on a scale Standard Error 0.25
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis Week 12	0.86 Units on a scale Standard Error 0.32	1.41 Units on a scale Standard Error 0.30
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis Week 24	1.07 Units on a scale Standard Error 0.32	1.64 Units on a scale Standard Error 0.30
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis Week 36	1.09 Units on a scale Standard Error 0.32	1.79 Units on a scale Standard Error 0.30
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis Week 52	1.17 Units on a scale Standard Error 0.31	1.88 Units on a scale Standard Error 0.29

Adverse Events

Single Blind Stabilization Phase

Serious events: 34 serious events

Other events: 148 other events

Deaths: 0 deaths

Brexpiprazole (Double-blind Maintenance Phase)

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo (Double-blnd Maintenance Phase)

Serious events: 11 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Single Blind Stabilization Phase n=464 participants at risk This single-blind stabilization phase was to titrate participants to a dose of brexpiprazole (1 to 4 mg/day) that would maintain stability of psychotic symptoms over 12 consecutive weeks (within a maximum of 36 weeks), while minimizing tolerability issues.	Brexpiprazole (Double-blind Maintenance Phase) n=97 participants at risk Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.	Placebo (Double-blnd Maintenance Phase) n=104 participants at risk Participants received placebo orally once daily for 52 weeks.
Investigations Weight increased	5.2% 24/464 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/97 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/104 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.
Nervous system disorders Akathisia	9.1% 42/464 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/97 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/104 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.
Nervous system disorders Headache	5.0% 23/464 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/97 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/104 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.
Psychiatric disorders Agitation	6.5% 30/464 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/97 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/104 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.
Nervous system disorders Insomnia	12.1% 56/464 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/97 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/104 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.
Nervous system disorders Schizophrenia	6.0% 28/464 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/97 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.	0.00% 0/104 • Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication. AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.

Additional Information

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Principal investigator is a sponsor employee
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