Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Doubleblind, Placebocontrolled Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole (OPC34712) as Maintenance Treatment in Adults with Schizophrenia.
Summary


EudraCT number 
201100576638 
Trial protocol 
RO 
Global end of trial date 
12 Feb 2015

Results information


Results version number 
v1(current) 
This version publication date 
27 Jul 2016

First version publication date 
27 Jul 2016

Other versions 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
33110232


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT01668797  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
Otsuka Pharmaceutical Development & Commercialization, Inc.


Sponsor organisation address 
2440 Research Boulevard, Rockville, Maryland, United States, 20850


Public contact 
Mary Hobart, Otsuka Pharmaceutical Development & Commercialization, Inc., +1 2406833194, Mary.Hobart@otsukaus.com


Scientific contact 
Mary Hobart, Otsuka Pharmaceutical Development & Commercialization, Inc., +1 2406833194, Mary.Hobart@otsukaus.com


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Results analysis stage


Analysis stage 
Interim


Date of interim/final analysis 
26 Jun 2015


Is this the analysis of the primary completion data? 
Yes


Primary completion date 
12 Feb 2015


Global end of trial reached? 
Yes


Global end of trial date 
12 Feb 2015


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
The primary objective of the study was to evaluate the efficacy of brexpiprazole compared with placebo as maintenance treatment in adults with schizophrenia.


Protection of trial subjects 
This trial was conducted in compliance with the protocol, ICHGCP and applicable local laws and regulatory requirements. Written informed consent was obtained from all participants (or their guardian or legal representative, as applicable according to local laws). Informed consent was obtained and documented prior to initiation of any procedures that were performed solely for the purpose of determining eligibility for this trial, including withdrawal from current medication(s). Participants were asked to sign a separate ICF designed for the purpose of collecting a onetime blood sample for assessment of cytochrome P450 (CYP) 2D6 metabolizer genotype. Participants were informed that they would not be excluded from the treatment trial if they did not wish to participate in the pharmacogenomic assessments.


Background therapy 
  
Evidence for comparator 
  
Actual start date of recruitment 
24 Oct 2012


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Colombia: 61


Country: Number of subjects enrolled 
Malaysia: 47


Country: Number of subjects enrolled 
Puerto Rico: 38


Country: Number of subjects enrolled 
Serbia: 78


Country: Number of subjects enrolled 
Turkey: 18


Country: Number of subjects enrolled 
Ukraine: 147


Country: Number of subjects enrolled 
United States: 204


Country: Number of subjects enrolled 
Romania: 73


Worldwide total number of subjects 
666


EEA total number of subjects 
73


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
666


From 65 to 84 years 
0


85 years and over 
0



Recruitment


Recruitment details 
A total of 753 participants were screened at 49 trial sites.  
Preassignment


Screening details 
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 (DoubleBlind 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.  
Period 1


Period 1 title 
Phase A and Phase B


Is this the baseline period? 
No  
Allocation method 
Not applicable


Blinding used 
Not blinded  
Arms


Are arms mutually exclusive 
Yes


Arm title

Phase A (Conversion Phase)  
Arm description 
The purpose of the openlabel conversion phase was 2fold: 1) to crosstitrate 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.  
Arm type 
Experimental  
Investigational medicinal product name 
Brexpiprazole


Investigational medicinal product code 

Other name 
OPC34712


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
All participants in the Conversion phase received brexpiprazole 1 mg/day as a starting dose and the dose was adjusted within the range of brexpiprazole 1 to 4 mg/day according to the study physician's judgment.


Arm title

Phase B (Stabilization Phase)  
Arm description 
This singleblind 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.  
Arm type 
Experimental  
Investigational medicinal product name 
Brexpiprazole


Investigational medicinal product code 

Other name 
OPC34712


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
All participants in this stabilization phase were titrated 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.




Period 2


Period 2 title 
Phase C


Is this the baseline period? 
Yes ^{[1]}  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Subject, Investigator  
Blinding implementation details 
The randomized treatments were administered in a doubleblind fashion with blocks of randomization numbers assigned to trial centers by the Interactive voice response system (IVRS)/ Interactive web response system (IWRS).


Arms


Are arms mutually exclusive 
Yes


Arm title

Phase C  Brexpiprazole (DoubleBlind Maintenance Phase)  
Arm description 
Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.  
Arm type 
Experimental  
Investigational medicinal product name 
Brexpiprazole


Investigational medicinal product code 

Other name 
OPC34712


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.


Arm title

Phase C  Placebo (DoubleBlind Maintenance Phase)  
Arm description 
Participants received placebo orally once daily for 52 weeks.  
Arm type 
Experimental  
Investigational medicinal product name 
Placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received placebo orally once daily for 52 weeks.


Notes [1]  Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: Period 1 is not baseline period as it consisted of Phase A and Phase B. Phase A was for conversion from other antipsychotics to oral brexpiprazole and washout of prohibited concomitant medications, if applicable. In addition, Phase B was a singleblind treatment phase to stabilize participants on oral brexpiprazole. 



Notes [2]  The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: All participants who signed the informed consent for the trial and entered the conversion phase or stabilization phase were included in the subjects enrolled per country table. However, the baseline period (Phase C) are those participants who were randomized to receive at least one dose of doubleblind study medication in the maintenance phase. [3]  The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: 346 participants entered Phase B; 346 rolled over from Phase A and 118 new patients entered into Phase B directly. 


Baseline characteristics reporting groups


Reporting group title 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase)


Reporting group description 
Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.  
Reporting group title 
Phase C  Placebo (DoubleBlind Maintenance Phase)


Reporting group description 
Participants received placebo orally once daily for 52 weeks.  



End points reporting groups


Reporting group title 
Phase A (Conversion Phase)


Reporting group description 
The purpose of the openlabel conversion phase was 2fold: 1) to crosstitrate 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.  
Reporting group title 
Phase B (Stabilization Phase)


Reporting group description 
This singleblind 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.  
Reporting group title 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase)


Reporting group description 
Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.  
Reporting group title 
Phase C  Placebo (DoubleBlind Maintenance Phase)


Reporting group description 
Participants received placebo orally once daily for 52 weeks. 


End point title 
Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.  
End point description 
The primary efficacy variable was time to impending relapse from randomization, as assessed by Clinical Global Impression of Improvement (CGII) 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) CGII 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) CGII 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 CSSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.


End point type 
Primary


End point timeframe 
From randomization to time of exacerbation of psychotic symptoms/impending relapse  up to 52 weeks




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
The total number of exacerbation of psychotic symptoms/impending relapse was estimated using a 1:1 (brexpiprazole: placebo) randomization ratio. For the primary endpoint, a 95% confidence interval for the hazard ratio (brexpiprazole vs. placebo) was provided using the Cox Proportional Hazard model with term of treatment in the model.


Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001 ^{[1]}  
Method 
Logrank  
Parameter type 
Hazard ratio (HR)  
Point estimate 
0.292


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.156  
upper limit 
0.548  
Notes [1]  The logrank test was based on time to exacerbation of psychotic symptoms/impending relapse. 


End point title 
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Doubleblind Maintenance Phase  
End point description 
Impending relapse was defined as meeting any of the following 5 criteria: 1) CGII 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) CGII 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 CSSRS (ie, an answer of "yes" to any of the questions on the suicidal behavior section of the CSSRS 5) Violent or aggressive behavior resulting in clinically significant selfinjury to another person, or property damage.


End point type 
Secondary


End point timeframe 
Baseline and Week 52/Early Termination




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
The percentage of participants with impending relapse in treatment groups (Brexpiprazole and placebo) in final analysis for participants meeting at least one of the criteria.


Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001  
Method 
Chisquared  
Confidence interval 


End point title 
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score  MMRM Analysis  
End point description 
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).


End point type 
Secondary


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.164  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.47


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.14  
upper limit 
0.19  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5466  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.04  
upper limit 
0.55  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.9417  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.81  
upper limit 
0.87  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.6257  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.25  
upper limit 
0.76  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.7437  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.68  
upper limit 
1.21  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4506  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.62  
upper limit 
0.28 


End point title 
Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase  
End point description 
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(CGIS) score ≤ 4 (moderately ill) AND 5) No current suicidal behavior as assessed by the ColumbiaSuicide Severity Rating Scale (CSSRS), defined as the following: An answer of "no" to each question on the Suicidal Behavior section of the CSSRS AND an answer of "no" to Questions 4 and 5 on the Suicidal Ideation section of the CSSRS, if completed, AND 6) No evidence of aggressive or violent behavior resulting in clinically significant selfinjury, injury to another person, property damage.


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2296  
Method 
Chisquared  
Confidence interval 

Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2051  
Method 
Chisquared  
Confidence interval 

Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.7354  
Method 
Chisquared  
Confidence interval 

Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1977  
Method 
Chisquared  
Confidence interval 

Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.8734  
Method 
Chisquared  
Confidence interval 


End point title 
Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score  MMRM Analysis  
End point description 
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7point 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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0664  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
3.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.82  
upper limit 
0.23  
Statistical analysis title 
Statistical analysis at Week 12  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0301  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
5.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
10.1  
upper limit 
0.52  
Statistical analysis title 
Statistical analysis at Week 24  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0226  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
4.77


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.86  
upper limit 
0.68  
Statistical analysis title 
Statistical analysis at Week 36  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0086  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
6.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
10.5  
upper limit 
1.59  
Statistical analysis title 
Statistical analysis at Week 52  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.28  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
6.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
18.1  
upper limit 
5.46  
Statistical analysis title 
Statistical analysis at across visits  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0011  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
4.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.01  
upper limit 
1.82 


End point title 
Mean Change From Baseline in PANSS Total Score  Lastobservationcarriedforward (LOCF) Analysis  
End point description 
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7point 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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0683  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.04


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.31  
upper limit 
0.23  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0174  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
5.05


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.2  
upper limit 
0.9  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0008  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
12  
upper limit 
3.18  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0005  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
8.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
12.4  
upper limit 
3.59  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0007  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
12.5  
upper limit 
3.41 


End point title 
Mean Change From Baseline in PANSS Positive Subscale Score  MMRM Analysis  
End point description 
PANSS consisted of three subscales: a total of 30 symptom constructs. For each construct, severity was rated on a 7point 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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Placebo (DoubleBlind Maintenance Phase) v Phase C  Brexpiprazole (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0507  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.23  
upper limit 
0  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.008  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.24  
upper limit 
0.5  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0215  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.56


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.89  
upper limit 
0.24  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0053  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.19  
upper limit 
0.58  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0339  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
2.71


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.2  
upper limit 
0.22  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.32  
upper limit 
0.88 


End point title 
Mean Change From Baseline in PANSS Positive Subscale Score  LOCF Analysis  
End point description 
PANSS consisted of three subscales: a total of 30 symptom constructs. For each construct, severity was rated on a 7point 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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1093  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
0.21  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0089  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.25  
upper limit 
0.47  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0005  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.74


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.26  
upper limit 
1.22  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.43  
upper limit 
1.44  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.7  
upper limit 
1.66 


End point title 
Mean Change From Baseline in PANSS Negative Subscale Score  MMRM Analysis  
End point description 
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7point 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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.165  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.69


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.66  
upper limit 
0.29  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.78


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.97  
upper limit 
0.42  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0939  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.07  
upper limit 
0.16  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1396  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.05


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.44  
upper limit 
0.35  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.847  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.43


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.14  
upper limit 
5  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2258  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.47


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.24  
upper limit 
0.3 


End point title 
Mean Change From Baseline in PANSS Negative Subscale Score  LOCF Analysis  
End point description 
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7point 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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0981  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.76


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.65  
upper limit 
0.14  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0264  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.22


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.3  
upper limit 
0.15  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0078  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.69  
upper limit 
0.42  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0101  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.57


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.77  
upper limit 
0.38  
Statistical analysis title 
Statistical analysis at Week 52  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0516  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.5  
upper limit 
0.01 


End point title 
Change From Baseline in Clinical Global ImpressionSeverity (CGIS) Score at Endpoint  MMRM Analysis  
End point description 
The severity of illness for each participant was rated using the CGIS scale. To assess CGIS, 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.


End point type 
Other prespecified


End point timeframe 
Weeks 2, 12, 24, 26 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0279  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.53  
upper limit 
0.03  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0117  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.39


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.68  
upper limit 
0.09  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0105  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.64  
upper limit 
0.09  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0007  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.56


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
0.25  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.078  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.09  
upper limit 
0.06  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0006  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.54  
upper limit 
0.15 


End point title 
Change From Baseline in CGIS Score at Endpoint  LOCF Analysis  
End point description 
The severity of illness for each participant was rated using the CGIS scale. To assess CGIS, 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.


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0284  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.03  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Placebo (DoubleBlind Maintenance Phase) v Phase C  Brexpiprazole (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0056  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.62  
upper limit 
0.11  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0002  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
0.24  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.56


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
0.3  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0002  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.53


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.79  
upper limit 
0.26 


End point title 
Clinical Global Impression  Improvement Score (CGII) at Endpoint  LOCF Analysis  
End point description 
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.


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0387  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
0.2  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0185  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.75  
upper limit 
0.07  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.97  
upper limit 
0.24  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0004  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.02  
upper limit 
0.3  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0009  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.96  
upper limit 
0.25 


End point title 
Mean Change From Baseline in Personal and Social Performance (PSP) Scale Score  MMRM Analysis  
End point description 
The PSP is a validated clinicianrated scale that measures personal and social functioning in four domains: socially useful activities (e.g., work and study), personal and social relationships, selfcare, 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 100point scale using algorithms to identify the appropriate 10point interval, and the rater's judgment to determine the total score within the 10point 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.


End point type 
Other prespecified


End point timeframe 
Weeks 24 and 52




Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.6525  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.47  
upper limit 
5.49  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1677  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
6.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.71  
upper limit 
14.87  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2347  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
3.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.41  
upper limit 
9.5 


End point title 
Mean Change From Baseline in PSP Scale Score  LOCF Analysis  
End point description 
The PSP is a validated clinicianrated scale that measures personal and social functioning in four domains: socially useful activities (e.g., work and study), personal and social relationships, selfcare, 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 100point scale using algorithms to identify the appropriate 10point interval, and the rater's judgment to determine the total score within the 10point 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.


End point type 
Other prespecified


End point timeframe 
Weeks 24 and 52




Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
194


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0285  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.79


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
7.17  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
194


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0071  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.31  
upper limit 
8.18 


End point title 
Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score  MMRM Analysis  
End point description 
The GAF is a clinicianrated scale that assesses the participant's psychological, social, and occupational functioning on a hypothetical continuum of mental healthillness 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.


End point type 
Other prespecified


End point timeframe 
Weeks 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.329  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.65  
upper limit 
4.88  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1756  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
2.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.22  
upper limit 
6.54  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0331  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
4.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.38  
upper limit 
8.63  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0522  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
5.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.06  
upper limit 
11.82  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0281  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
3.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.41  
upper limit 
6.92 


End point title 
Mean Change From Baseline in GAF Scale Score  LOCF Analysis  
End point description 
The GAF is a clinicianrated scale that assesses the participant's psychological, social, and occupational functioning on a hypothetical continuum of mental healthillness 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.


End point type 
Other prespecified


End point timeframe 
Weeks 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
197


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0111  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
6.86  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
197


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0014  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
5.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
8.62  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
197


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
6.81


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.61  
upper limit 
10  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
197


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
6.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.28  
upper limit 
9.83 


End point title 
Percentage of Participants Who Discontinued Due to All Causes  
End point description 
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 Doubleblind Maintenance phase. The trial was completed by sponsor when efficacy was demonstrated at the first prespecified interim analysis (45 impending relapse events) performed by an independent (unblinded) statistician.


End point type 
Other prespecified


End point timeframe 
Baseline to Week 52




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
Statistical analysis for participants who discontinued due to all causes.


Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0014  
Method 
Logrank  
Confidence interval 


End point title 
Mean Change From Baseline in PANSS Excited Component (PEC) Score  MMRM Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1577  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.43


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.02  
upper limit 
0.17  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1685  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.61  
upper limit 
0.28  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2815  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.43  
upper limit 
0.42  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0286  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.16  
upper limit 
0.12  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1803  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.58  
upper limit 
0.51  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0077  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.65


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.12  
upper limit 
0.17 


End point title 
Mean Change From Baseline in PEC Score  LOCF Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1852  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.06  
upper limit 
0.21  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.143  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.63


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.47  
upper limit 
0.21  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0323  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.06  
upper limit 
0.09  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0071  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.31  
upper limit 
0.37  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0023  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.54


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.52  
upper limit 
0.56 


End point title 
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score  MMRM Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0288  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.54  
upper limit 
0.14  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0128  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
2.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.6  
upper limit 
0.44  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0462  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.15  
upper limit 
0.03  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0074  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
2.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.94  
upper limit 
0.64  
Statistical analysis title 
Statistical analysis at Week 52  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0136  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
3.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.05  
upper limit 
0.75  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.84  
upper limit 
0.97 


End point title 
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score  LOCF Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Placebo (DoubleBlind Maintenance Phase) v Phase C  Brexpiprazole (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0695  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.26  
upper limit 
0.09  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0089  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.38  
upper limit 
0.49  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0004  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.83


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.39  
upper limit 
1.27  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.63  
upper limit 
1.54  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.0001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.99  
upper limit 
1.89 


End point title 
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score  MMRM Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1969  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.66  
upper limit 
0.35  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2007  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.04  
upper limit 
0.43  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0436  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.3  
upper limit 
0.03  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0444  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.97  
upper limit 
0.04  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.8927  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.4  
upper limit 
5.02  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2154  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.52


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.34  
upper limit 
0.31 


End point title 
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score  LOCF Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0707  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.85


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.78  
upper limit 
0.07  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0276  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.35  
upper limit 
0.14  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0065  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.72  
upper limit 
0.45  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0085  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.63


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.84  
upper limit 
0.42  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.063  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.52  
upper limit 
0.07 


End point title 
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score  MMRM Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Placebo (DoubleBlind Maintenance Phase) v Phase C  Brexpiprazole (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2251  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.33  
upper limit 
0.31  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0368  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.19  
upper limit 
0.07  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0024  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.53


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.51  
upper limit 
0.56  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0293  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.8  
upper limit 
0.15  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.9632  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.32  
upper limit 
3.17  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0029  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.99


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.63  
upper limit 
0.34 


End point title 
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score  LOCF Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1062  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.65


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.44  
upper limit 
0.14  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0051  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.33  
upper limit 
0.42  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0001  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.05


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.08  
upper limit 
1.01  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0004  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3  
upper limit 
0.89  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0035  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.69


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.81  
upper limit 
0.56 


End point title 
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score  MMRM Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1465  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.85  
upper limit 
0.13  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2154  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.49


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.27  
upper limit 
0.29  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2696  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.23  
upper limit 
0.35  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0179  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.95  
upper limit 
0.19  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0875  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.46  
upper limit 
0.18  
Statistical analysis title 
Statistical analysis at across visits.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0021  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.08  
upper limit 
0.24 


End point title 
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score  LOCF Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2135  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.86  
upper limit 
0.19  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2437  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.13  
upper limit 
0.29  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0635  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.81


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.66  
upper limit 
0.05  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0144  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.92  
upper limit 
0.22  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0046  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.12  
upper limit 
0.39 


End point title 
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score  LOCF Analysis  
End point description 
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).


End point type 
Other prespecified


End point timeframe 
Weeks 6, 12, 24, 36 and 52




Statistical analysis title 
Statistical analysis at Week 6.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0467  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.67


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.32  
upper limit 
0.06  
Statistical analysis title 
Statistical analysis at Week 12.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1599  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.33  
upper limit 
0.22  
Statistical analysis title 
Statistical analysis at Week 24.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1417  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.58


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.35  
upper limit 
0.19  
Statistical analysis title 
Statistical analysis at Week 36.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0724  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.47  
upper limit 
0.06  
Statistical analysis title 
Statistical analysis at Week 52.  
Comparison groups 
Phase C  Brexpiprazole (DoubleBlind Maintenance Phase) v Phase C  Placebo (DoubleBlind Maintenance Phase)


Number of subjects included in analysis 
200


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0608  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.72


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.47  
upper limit 
0.03 


Adverse events information


Timeframe for reporting adverse events 
Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a followup phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication.


Adverse event reporting additional description 
AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to doubleblind treatment (brexpiprazole or placebo) and received at least one dose of doubleblind study medication in DoubleBlind Maintenance Phase.


Assessment type 
Nonsystematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
17.0


Reporting groups


Reporting group title 
Single Blind Stabilization Phase


Reporting group description 
This singleblind 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.  
Reporting group title 
Brexpiprazole (Doubleblind Maintenance Phase)


Reporting group description 
Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.  
Reporting group title 
Placebo (Doubleblnd Maintenance Phase)


Reporting group description 
Participants received placebo orally once daily for 52 weeks.  


Frequency threshold for reporting nonserious adverse events: 5%  



Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? No  
Interruptions (globally) 

Were there any global interruptions to the trial? No  
Limitations and caveats 

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.  
As the interim analysis results were positive, the trial was completed as it achieved the primary endpoint of a significant delay in time to impending relapse for participants randomized to brexpiprazole when compared to participants in placebo. 