Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Doubleblind, Placebocontrolled Trial of the Safety and Efficacy of Two Fixed Doses of OPC34712 as Adjunctive Therapy in the Treatment of Adults with Major Depressive Disorder, the Polaris Trial.
Summary


EudraCT number 
201100134933 
Trial protocol 
DE HU 
Global end of trial date 
12 Sep 2013

Results information


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

First version publication date 
02 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 
33110227


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT01360632  
WHO universal trial number (UTN) 
  
Other trial identifiers 
IND No. : 103,958  
Sponsors


Sponsor organisation name 
Otsuka Pharmaceutical Development & Commercialization, Inc.


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


Date of interim/final analysis 
04 Jun 2014


Is this the analysis of the primary completion data? 
Yes


Primary completion date 
12 Sep 2013


Global end of trial reached? 
Yes


Global end of trial date 
12 Sep 2013


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
To compare the efficacy of OPC34712 (1.0 and 3.0 milligrams (mg)/day) to placebo as adjunctive therapy to an assigned openlabel antidepressant therapy (ADT) in participants who demonstrated an incomplete response after 8 weeks of prospective treatment with the same assigned openlabel ADT.


Protection of trial subjects 
This trial was conducted in compliance with Good Clinical Practice (GCP) guidelines for conducting, recording, and reporting trials, as well as for archiving essential documents. Consistent with ethical principles for the protection of human research subjects, no trial procedures were performed on trial candidates until written consent had been obtained from them. The informed consent form (ICF), protocol, and amendments for this trial were submitted to and approved by the institutional review board (IRB) or independent ethics committee (IEC) for each respective trial site or country.


Background therapy 
At enrollment the physician carefully considered the participants’s antidepressant treatment (ADT) history and made an ADT assignment for each enrolled participant from the following list of sponsorprovided ADTs: escitalopram, fluoxetine, paroxetine controlled release (CR), sertraline, duloxetine, and venlafaxine extended release (XR). Once assigned to one of these ADTs by the physician in Phase A, participants remained on that ADT for the duration of the trial (ie, baseline through Week 14/end of treatment) or were withdrawn if a change in ADT was needed.  
Evidence for comparator 
  
Actual start date of recruitment 
25 Jun 2011


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 
Romania: 12


Country: Number of subjects enrolled 
Germany: 77


Country: Number of subjects enrolled 
Hungary: 28


Country: Number of subjects enrolled 
Canada: 15


Country: Number of subjects enrolled 
Russian Federation: 48


Country: Number of subjects enrolled 
Ukraine: 55


Country: Number of subjects enrolled 
United States: 442


Worldwide total number of subjects 
677


EEA total number of subjects 
117


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) 
676


From 65 to 84 years 
1


85 years and over 
0



Recruitment


Recruitment details 
The study was conducted in 1539 participants at 92 trial sites in 7 countries. A total of 677 participants were into Phase B (period 2) and 675 received treatment.  
Preassignment


Screening details 
The study consisted of a 7 to 28day Screening period, an 8Week singleblind placebo + ADT prospective PhaseA, a 6Week doubleblind randomization PhaseB or singleblind Phase A+ for those participants who did not meet criteria for randomization and a Followup of 30 (+2) days after the last dose of study medication.  
Period 1


Period 1 title 
Overall Study (overall period)


Is this the baseline period? 
Yes  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Subject, Investigator  
Blinding implementation details 
Treatment assignment code list was available to an independent biostatistician and access to randomized treatment codes restricted to personnel charged with generating/ maintaining randomization files, packaging doubleblind treatment, operating interactive voice recognition system and reporting serious adverse events (SAEs) to regulatory agencies. All other trial personnel remained blinded to the identity of the treatment until every participant had completed treatment and the database locked.


Arms


Are arms mutually exclusive 
Yes


Arm title

Brexpiprazole (1mg) + ADT  
Arm description 
Participants were administered brexpiprazole (1mg/day) as an adjunctive therapy to an assigned open label ADT (antidepressant therapy).  
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 
Brexpiprazole 1mg/day as an adjunctive therapy to an assigned open label ADT.


Arm title

Brexpiprazole (3mg) + ADT  
Arm description 
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned openlabel ADT.  
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 
Brexpiprazole 3mg/day as an adjunctive therapy to an assigned openlabel ADT.


Arm title

Placebo +ADT  
Arm description 
Participants were administered placebo daily as an adjunctive therapy to an open label ADT.  
Arm type 
Placebo  
Investigational medicinal product name 
Placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Placebo daily as adjunctive therapy to an open label ADT.





Baseline characteristics reporting groups


Reporting group title 
Brexpiprazole (1mg) + ADT


Reporting group description 
Participants were administered brexpiprazole (1mg/day) as an adjunctive therapy to an assigned open label ADT (antidepressant therapy).  
Reporting group title 
Brexpiprazole (3mg) + ADT


Reporting group description 
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned openlabel ADT.  
Reporting group title 
Placebo +ADT


Reporting group description 
Participants were administered placebo daily as an adjunctive therapy to an open label ADT.  



End points reporting groups


Reporting group title 
Brexpiprazole (1mg) + ADT


Reporting group description 
Participants were administered brexpiprazole (1mg/day) as an adjunctive therapy to an assigned open label ADT (antidepressant therapy).  
Reporting group title 
Brexpiprazole (3mg) + ADT


Reporting group description 
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned openlabel ADT.  
Reporting group title 
Placebo +ADT


Reporting group description 
Participants were administered placebo daily as an adjunctive therapy to an open label ADT.  
Subject analysis set title 
Efficacy Sample


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
All participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MontgomeryAsberg Depression Rating Scale (MADRS) Total Score in Phase B.


Subject analysis set title 
Efficacy Sample Per Protocol Amendment 3


Subject analysis set type 
Per protocol  
Subject analysis set description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.



End point title 
Mean change from the end of Phase A (Week 8 visit) to Phase B (Week 14 visit) in the MontgomeryAsberg Depression Rating Scale for the Efficacy Sample Set  
End point description 
The MADRS was utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the “best” rating and 6 being the “worst” rating. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. The MADRS Total Score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60, with higher values indicating worse outcome.


End point type 
Primary


End point timeframe 
Baseline and Week 14




Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The primary analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0925  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.58  
upper limit 
0.2  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The primary analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0327  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.52


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.92  
upper limit 
0.13 


End point title 
Mean Change in MADRS Total Score from Baseline End of Week 8 to Week 14 for the Efficacy Sample per final protocol  
End point description 
The MADRS was utilized as the primary efficacy assessment of a participants level of depression. The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the “best” rating and 6 being the “worst” rating. The possible total scores were from 0 to 6. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. Analysis was based on all participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.


End point type 
Primary


End point timeframe 
Baseline and Week 14




Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The primary analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0737  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.73  
upper limit 
0.13  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The primary analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0079  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.39  
upper limit 
0.51 


End point title 
Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in Sheehan Disability Scale (SDS) Mean Scores for the Efficacy Sample Set  
End point description 
This is the key secondary outcome measure. The SDS was a selfrated instrument used to measure the effect of the participants symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores ranged from 0 through 10. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0= not at all to 10= extremely. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS score were calculated over the three item scores. All three item scores were needed to be available with the exception of the work/school item score when this item was not applicable. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation.


End point type 
Secondary


End point timeframe 
Week 11 and Week 14




Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0091  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.49


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
0.12  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0474  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
0  
Statistical analysis title 
Statistical analysis 3 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0008  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
0.23  
Statistical analysis title 
Statistical analysis 4 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5792  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.41  
upper limit 
0.23 


End point title 
Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in SDS Mean Scores for the Efficacy Sample per final protocol  
End point description 
The SDS was a selfrated instrument used to measure the effect of the participants symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores ranged from 0 through 10. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0= not at all, to 10= extremely. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS score were calculated over the three item scores. All three item scores were needed to be available with the exception of the work/school item score when this item was not applicable. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.


End point type 
Secondary


End point timeframe 
Week 11 and Week 14




Statistical analysis title 
Statisical analysis 1 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0158  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.49


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.89  
upper limit 
0.09  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0191  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.88  
upper limit 
0.08  
Statistical analysis title 
Statistical analysis 3 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0015  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.58


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.94  
upper limit 
0.22  
Statistical analysis title 
Statistical analysis 4 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2627  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.21


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.56  
upper limit 
0.15 


End point title 
Mean change from end of Phase A (Week 8 visit) in MADRS Total Score for every Study Week visit in Phase B other than Week 14 visit for the Efficacy Sample Set  
End point description 
The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the “best” rating and 6 being the “worst” rating. The possible total scores were from 0 to 6. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.


End point type 
Secondary


End point timeframe 
Week 8 to Week 13




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0096  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.86  
upper limit 
0.26  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4137  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.14  
upper limit 
0.47  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0065  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.47  
upper limit 
0.4  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0914 ^{[1]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.93  
upper limit 
0.14  
Notes [1]  MMRM method with an unstructured variance covariance matrix was used, with model terms trial site, treatment group, visit, treatment groupbyvisit and Baselinebyvisit interaction. 

Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0139  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.39


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.5  
upper limit 
0.28  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2097  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.71


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.82  
upper limit 
0.4  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0099  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.56


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.75  
upper limit 
0.38  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.034  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.48  
upper limit 
0.1  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0177  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.53


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.8  
upper limit 
0.27  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0085  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.71


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.98  
upper limit 
0.44 


End point title 
Mean Change from end of Phase A (Week 8 visit) in MADRS Total Score for every Study Week visit in Phase B other than Week 14 visit for the Efficacy Sample per final protocol  
End point description 
The MADRS consisted of 10 items, all rated on a 0 to 6 scale with 0 being the “best” rating and 6 being the “worst” rating. The possible total scores were from 0 to 6. The MADRS total score were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3


End point type 
Secondary


End point timeframe 
Week 8 to Week 13




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0286  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.92


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.74  
upper limit 
0.1  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.3173  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.24  
upper limit 
0.4  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0313  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.23  
upper limit 
0.11  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0732  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.97


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.04  
upper limit 
0.09  
Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0206  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.51  
upper limit 
0.21  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1233  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.06  
upper limit 
0.25  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0097  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.84  
upper limit 
0.39  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0092  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.63


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.86  
upper limit 
0.41  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0139  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.63


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.94  
upper limit 
0.33  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0015  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
2.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.42  
upper limit 
0.81 


End point title 
Mean change from end of Phase A (Week 8 visit) to every study week visit in Phase B in Clinical Global Impression Severity of Illness (CGIS) for the Efficacy Sample Set  
End point description 
The severity of illness for each participant was rated using the CGIS. To perform this assessment, the study physician had to answer 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 at all ill; 2 =
borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0436  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.18  
upper limit 
0  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1741  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.15  
upper limit 
0.03  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0012  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.21


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.34  
upper limit 
0.08  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0266  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.27  
upper limit 
0.02  
Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0034  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.33  
upper limit 
0.07  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.3053  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.06  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0541  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.29  
upper limit 
0  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0912  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.28  
upper limit 
0.02  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1553  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.28  
upper limit 
0.04  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1855  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.27  
upper limit 
0.05  
Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2015  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.28  
upper limit 
0.06  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0852  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.32  
upper limit 
0.02 


End point title 
Mean change from end of Phase A (Week 8 visit) to every study week visit in Phase B Week in Clinical CGIS for the Efficacy Sample per final protocol  
End point description 
The severity of illness for each participant was rated using the CGIS. To perform this assessment, the study physician had to answer 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 at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0817  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.17  
upper limit 
0.01  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1406  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.16  
upper limit 
0.02  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.011  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.29  
upper limit 
0.04  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0287  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.27  
upper limit 
0.02  
Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0071  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.32  
upper limit 
0.05  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2503  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.22  
upper limit 
0.06  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0539  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0398  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.31  
upper limit 
0.01  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1168  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.03  
Statistical analysis title 
Statistical anaysis 2 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0621  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.32  
upper limit 
0.01  
Statistical analysis title 
Statisical analysis 1 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.089  
Method 
Mixed models analysis  
Parameter type 
Median difference (final values)  
Point estimate 
0.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.32  
upper limit 
0.02  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0213  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.38  
upper limit 
0.03 


End point title 
Mean change from end of Phase A (Week 8 visit) for every study week visit in Phase B in Inventory of Depressive Symptomatology (SelfReport) IDSSR Total Score for the Efficacy Sample Set  
End point description 
IDSSR was a 30item selfreport measured to assess core diagnostic depressive symptoms and atypical and melancholic symptom features of major depressive disorders. The IDSSR consists of 30 items, all rated on a 0 to 3 scale with 0 being the “best” rating and 3 being the “worst” rating. Besides item 9, two subitems 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two subitems were not included in the calculation of the total score. The IDSSR Total Score was the sum of ratings of 28 item scores. The possible IDSSR Total Score ranged from 0 to 84. The IDSSR Total Score was unevaluable if less than 23 of the 28 items were recorded. If the number of items recorded was at least 23 and at most 27, the IDSSR Total Score was the mean of the recorded items multiplied by 28, and was then rounded off to the first decimal place.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0228  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.37  
upper limit 
0.18  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5081  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.47  
upper limit 
0.73  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0064  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.2  
upper limit 
0.53  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1898  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.23  
upper limit 
0.44  
Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0074  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
2.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.62  
upper limit 
0.56  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5935  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.95  
upper limit 
1.11  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0211  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.52  
upper limit 
0.29  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1031  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.96  
upper limit 
0.27  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1366  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.02  
upper limit 
0.41  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2709  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.96


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.68  
upper limit 
0.75  
Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0812  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.4  
upper limit 
0.2  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1001  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.52


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.33  
upper limit 
0.29 


End point title 
Mean change from end of Phase A (Week 8 visit) for every study week visit in Phase B in IDSSR Total Score for the Efficacy Sample per final protocol  
End point description 
The IDSSR was a 30item selfreport measured to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorders. The IDSSR consists of 30 items, all rated on a 0 to 3 scale with 0 being the “best” rating and 3 being the “worst” rating. Besides item 9, two subitems 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two subitems were not included in the calculation of the total score. The IDSSR Total Score was the sum of ratings of 28 item scores. The possible IDSSR Total Score ranged from 0 to 84. The IDSSR Total Score was unevaluable if less than 23 of the 28 items were recorded. If the number of items recorded was at least 23 and at most 27, the IDSSR Total Score was the mean of the recorded items multiplied by 28, and was then rounded off to the first decimal place.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0496  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.24  
upper limit 
0  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.387  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.49


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.61  
upper limit 
0.63  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0125  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.13  
upper limit 
0.38  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0898  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.57  
upper limit 
0.19  
Statistical analysis title 
Statitical analysis 1 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
2.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.88  
upper limit 
0.74  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.301 ^{[2]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.83


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
0.74  
Notes [2]  MMRM method with an unstructured variance covariance matrix was used, with model terms trial site, treatment group, visit, treatment groupbyvisit and Baselinebyvisit interaction. 

Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0118  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
2.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.82  
upper limit 
0.48  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0287  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.54  
upper limit 
0.19  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0686  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.63


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.39  
upper limit 
0.12  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.056  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.72


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.47  
upper limit 
0.04  
Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0448  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.75  
upper limit 
0.04  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0251  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
2.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.98  
upper limit 
0.27 


End point title 
Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) Hamilton Depression Scale 17 Item Version (HAM)D17 Total Score for the Efficacy Sample Set  
End point description 
The HAMD17 was utilized as a secondary assessment of a participants level of depression. The HAMD (17Item) consisted of 17 items. Eight items were rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) were rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 was the “best” rating and the highest score (2 or 4) was the “worst” rating. The possible total scores were from 0 to 52. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.


End point type 
Secondary


End point timeframe 
Baseline and Week 14




Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The last observation carried forward (LOCF) method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1732 ^{[3]}  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.67


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.63  
upper limit 
0.29  
Notes [3]  ANCOVA model, with treatment as main effects, study centre and Week 8 value as covariates 

Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
433


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0066 ^{[4]}  
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  
Notes [4]  ANCOVA model, with treatment as main effects, study centre and Week 8 value as covariates 


End point title 
Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in HAMD17 Total Score for the Efficacy Sample Set per final protocol  
End point description 
The HAMD17 was utilized as a secondary assessment of a participants level of depression. The HAMD (17Item) consisted of 17 items. Eight items were rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) were rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 was the “best” rating and the highest score (2 or 4) was the “worst” rating. The possible total scores were from 0 to 52. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.


End point type 
Secondary


End point timeframe 
Baseline and Week 14




Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
406


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1226 ^{[5]}  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.78


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.78  
upper limit 
0.21  
Notes [5]  ANCOVA model, with treatment as main effects, study centre and Week 8 value as covariates 

Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
405


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[6]}  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.69


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.69  
upper limit 
0.68  
Notes [6]  ANCOVA model, with treatment as main effects, study centre and Week 8 value as covariates 


End point title 
Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in Hamilton Anxiety Rating Scale (HAMA) Total Score for the Efficacy Sample Set  
End point description 
The HAMA is utilized for the evaluation of anxiety symptoms. The HAMA consists of 14 items. Each item is rated on a 0 to 4 scale. For all of these items, 0 is the “best” rating and 4 is the “worst” rating. If no item scores are missing, then the HAMA total score is the sum of all 14 item scores. The possible total scores are from 0 to 56. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.


End point type 
Secondary


End point timeframe 
Week 14




Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
430


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.8164 ^{[7]}  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.93  
upper limit 
0.73  
Notes [7]  ANCOVA model, with treatment as main effects, study centre and Week 8 value as covariates 

Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
426


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1939 ^{[8]}  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.39  
upper limit 
0.28  
Notes [8]  ANCOVA model, with treatment as main effects, study centre and Week 8 value as covariate 


End point title 
Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in HAMA Total for the Efficacy Sample per final protocol  
End point description 
The HAMA is utilized for the evaluation of anxiety symptoms. The HAMA consists of 14 items. Each item is rated on a 0 to 4 scale. For all of these items, 0 is the “best” rating and 4 is the “worst” rating. If no item scores are missing, then the HAMA total score is the sum of all 14 item scores. The possible total scores are from 0 to 56. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.


End point type 
Secondary


End point timeframe 
Baseline and Week 14




Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
401


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5192 ^{[9]}  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.14  
upper limit 
0.57  
Notes [9]  ANCOVA model, with treatment as main effects, study centre and Week 8 value as covariates 

Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
399


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0443 ^{[10]}  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.75  
upper limit 
0.02  
Notes [10]  ANCOVA model, with treatment as main effects, study centre and Week 8 value as covariates 


End point title 
Mean CGII Score at each trial week visit in Phase B for the Efficacy Sample Set  
End point description 
The efficacy of study medication was rated for each participant using the CGII. The study physician would rate the participant's total improvement whether or not it is due entirely to drug treatment. Response choices included: 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. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0248 ^{[11]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.26  
upper limit 
0.02  
Notes [11]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1334 ^{[12]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.22  
upper limit 
0.03  
Notes [12]  Pvalue and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center. 

Statistical analysis title 
Statisitcal analysis 1 at Week 10  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0009 ^{[13]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.42  
upper limit 
0.11  
Notes [13]  Pvalue and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center. 

Statistical analysis title 
Statisitcal analysis 2 at Week 10  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0019 ^{[14]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.38  
upper limit 
0.09  
Notes [14]  Pvalue and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center 

Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0009 ^{[15]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.42  
upper limit 
0.11  
Notes [15]  Pvalue and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center 

Statistical analysis title 
Statisitcal analysis 2 at Week 11  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0254 ^{[16]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.34  
upper limit 
0.02  
Notes [16]  Pvalue and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0035 ^{[17]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.41  
upper limit 
0.08  
Notes [17]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0152 ^{[18]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.21


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.39  
upper limit 
0.04  
Notes [18]  Pvalue and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004 ^{[19]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.42  
upper limit 
0.08  
Notes [19]  Pvalue and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.013 ^{[20]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.42  
upper limit 
0.05  
Notes [20]  Pvalue and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center. 

Statistical analysis title 
Statisitical analysis 1 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0755 ^{[21]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.33  
upper limit 
0.02  
Notes [21]  Pvalue and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center 

Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0527 ^{[22]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.39  
upper limit 
0  
Notes [22]  Pvalue and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center 


End point title 
Mean CGII Score at each trial week visit in Phase B for the Efficacy Sample per final protocol  
End point description 
The efficacy of study medication was rated for each participant using the CGII. The study physician would rate the participant's total improvement whether or not it is due entirely to drug treatment. Response choices included: 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. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0275 ^{[23]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.26  
upper limit 
0.01  
Notes [23]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statisitcal analysis 2 at Week 9  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1583 ^{[24]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.22  
upper limit 
0.04  
Notes [24]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0021 ^{[25]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.41  
upper limit 
0.09  
Notes [25]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0018 ^{[26]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.09  
Notes [26]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0011 ^{[27]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.43  
upper limit 
0.11  
Notes [27]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0021 ^{[28]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.44  
upper limit 
0.1  
Notes [28]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0111 ^{[29]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.42  
upper limit 
0.05  
Notes [29]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.44  
upper limit 
0.09  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0046 ^{[30]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.09  
Notes [30]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0237 ^{[31]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.21


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.39  
upper limit 
0.03  
Notes [31]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0171 ^{[32]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.45  
upper limit 
0.04  
Notes [32]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 

Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0235 ^{[33]}  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
0.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.36  
upper limit 
0.03  
Notes [33]  Pvalue and treatment difference (CI) are derived from CochranMantelHaenszel (CMH) row mean scores statistics controlling for study center. 


End point title 
Percentage of participants with a MADRS response during Phase B relative to the end of Phase A (Week 8 visit) for the Efficacy Sample Set.  
End point description 
MADRS response was defined as >=50 percent reduction in MADRS Total Score from end of Phase A (Week 8). The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5279  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.51  
upper limit 
3.68  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0141  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
0.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.02  
upper limit 
0.94  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0484  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
1.92


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.99  
upper limit 
3.72  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5813  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
2.5  
Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1236  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
2.54  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.
The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4998  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.21


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
2.1  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0365  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.64


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.03  
upper limit 
2.61  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0822  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.52


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.95  
upper limit 
2.43  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4049  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.79  
upper limit 
1.78  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2951  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
1.8  
Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0248  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.53


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.06  
upper limit 
2.2  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0326  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.03  
upper limit 
2.21 


End point title 
Percentage of participants with a MADRS response during Phase B relative to the end of Phase A (Week 8 visit) for the Efficacy Sample per final protocol  
End point description 
MADRS response was defined as >=50 percent reduction in MADRS Total Score from end of Phase A (Week 8). All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.7993  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
0.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
2.55  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0118  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.01  
upper limit 
0.93  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2825  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.71  
upper limit 
3.16  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.6375  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.58  
upper limit 
2.5  
Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0923  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.92  
upper limit 
2.82  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.3812  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
2.3  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0464  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.63


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
2.65  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.049  
Method 
CochranMantelHaenszel  
Parameter type 
Mean difference (final values)  
Point estimate 
1.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
2.64  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2124  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.32


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.85  
upper limit 
2.06  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1078  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.93  
upper limit 
2.14  
Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0094  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.69


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.14  
upper limit 
2.5  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0162  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.65


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.09  
upper limit 
2.5 


End point title 
Percentage of participants with a MADRS Remission during Phase B relative to the end of Phase A (Week 8) for the Efficacy Sample Set.  
End point description 
MADRS remission was defined as a < or equal to 10 and > or equal to 50% reduction in MADRS Total Score from end of Phase A (Week 8). The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.


End point type 
Secondary


End point timeframe 
Week to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.9498  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.37  
upper limit 
2.9  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0141  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
0.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.02  
upper limit 
0.94  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.8609  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
0.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
2.17  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2846  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
0.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.22  
upper limit 
1.54  
Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.248  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.75  
upper limit 
2.99  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.7513  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.54  
upper limit 
2.37  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0554  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.99  
upper limit 
3.35  
Statistical analysis title 
Statisitcal analysis 2 ar Week 12  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2409  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
2.87  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5538  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.69  
upper limit 
2.02  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1743  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.85  
upper limit 
2.41  
Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
436


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2843  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.81  
upper limit 
2.07  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
435


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.464  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.74  
upper limit 
1.92 


End point title 
Percentage of participants with a MADRS Remission during Phase B relative to the end of Phase A (Week 8) for the Efficacy Sample per final protocol  
End point description 
MADRS remission was defined as a < or equal to 10 and > or equal to 50% reduction in MADRS Total Score from end of Phase A (Week 8). All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.3867  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.18  
upper limit 
1.97  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0118  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.01  
upper limit 
0.93  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.32  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
0.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.21  
upper limit 
1.66  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.3266  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.23  
upper limit 
1.62  
Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.3027  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.47


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
3.1  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.696  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.54  
upper limit 
2.52  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1368  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.86  
upper limit 
3.07  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2387  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
2.89  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4498  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.69  
upper limit 
2.28  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1009  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.91  
upper limit 
2.82  
Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1499  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.45


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
2.41  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.3012  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of remission rate  
Point estimate 
1.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.78  
upper limit 
2.18 


End point title 
Percentage of participants with a CGII response during Phase B relative to the end of Phase A (Week 8 visit) for the Efficacy Sample Set  
End point description 
A CGII response was defined as a CGII score of 1 (very much improved) or 2 (much improved). The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2873  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.75  
upper limit 
2.65  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2677  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.79  
upper limit 
2.36  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0031  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.21  
upper limit 
2.68  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0066  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.15  
upper limit 
2.5  
Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0665  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.98  
upper limit 
1.83  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.025  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.05  
upper limit 
1.91  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.2224  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
1.54  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0369  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.01  
upper limit 
1.68  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0179  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.05  
upper limit 
1.75  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0011  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.49


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.17  
upper limit 
1.89  
Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.3249  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.89  
upper limit 
1.41  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0122  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.06  
upper limit 
1.66 


End point title 
Percentage of participants with a CGII response during Phase B relative to the end of Phase A (Week 8 visit) for the Efficacy Sample per final protocol  
End point description 
A CGII response was defined as a CGII score of 1 (very much improved) or 2 (much improved). All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.


End point type 
Secondary


End point timeframe 
Week 8 to Week 14




Statistical analysis title 
Statistical analysis 1 at Week 9  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5836  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.22


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
2.49  
Statistical analysis title 
Statistical analysis 2 at Week 9  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.3792  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
2.37  
Statistical analysis title 
Statistical analysis 1 at Week 10  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0101  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.77


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.14  
upper limit 
2.74  
Statistical analysis title 
Statistical analysis 2 at Week 10  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0065  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.17  
upper limit 
2.63  
Statistical analysis title 
Statistical analysis 1 at Week 11  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0526  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
1.99  
Statistical analysis title 
Statistical analysis 2 at Week 11  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0156  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.08  
upper limit 
2.11  
Statistical analysis title 
Statistical analysis 1 at Week 12  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1689  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.22


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.92  
upper limit 
1.63  
Statistical analysis title 
Statistical analysis 2 at Week 12  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0231  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.04  
upper limit 
1.8  
Statistical analysis title 
Statistical analysis 1 at Week 13  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0175  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.06  
upper limit 
1.84  
Statistical analysis title 
Statistical analysis 2 at Week 13  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0004  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.22  
upper limit 
2.07  
Statistical analysis title 
Statistical analysis 1 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
414


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1396  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.21


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.94  
upper limit 
1.55  
Statistical analysis title 
Statistical analysis 2 at Week 14  
Statistical analysis description 
All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
416


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0016  
Method 
CochranMantelHaenszel  
Parameter type 
Ratio of response rate  
Point estimate 
1.46


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.15  
upper limit 
1.86 


End point title 
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set  
End point description 
The SDS is a selfrated instrument used to measure the effect of the patient’s symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.


End point type 
Secondary


End point timeframe 
Week 11 and Week 14




Statistical analysis title 
Statistical analysis 1  
Statistical analysis description 
For Item: Work/School: Week 11. The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0377  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.45


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.88  
upper limit 
0.03  
Statistical analysis title 
Statistical analysis 2  
Statistical analysis description 
For Item: Work/School: Week 14 . The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0741  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.43


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.91  
upper limit 
0.04  
Statistical analysis title 
Statistical analysis 3  
Statistical analysis description 
For Item: Work/School: Week 11. The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0966  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.07  
upper limit 
0.81  
Statistical analysis title 
Statistical analysis 4  
Statistical analysis description 
For Item: Work/School: Week 14. The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4774  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.66  
upper limit 
0.31  
Statistical analysis title 
Statistical analysis 5  
Statistical analysis description 
Social life: Week 11. The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0263  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
0.05  
Statistical analysis title 
Statistical analysis 6  
Statistical analysis description 
Social life: Week 14. The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0214  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.89  
upper limit 
0.07  
Statistical analysis title 
Statistical analysis 7  
Statistical analysis description 
Social life: Week 11. The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.8281  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.04


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.32  
Statistical analysis title 
Statistical analysis 8  
Statistical analysis description 
Social life: Week 14. The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.054  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
0.01  
Statistical analysis title 
Statistical analysis 9  
Statistical analysis description 
Family life: Week 11. The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0008  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.63


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.99  
upper limit 
0.26  
Statistical analysis title 
Statistical analysis 10  
Statistical analysis description 
Family life: Week 14. The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (1mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
443


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0093  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.97  
upper limit 
0.14  
Statistical analysis title 
Statistical analysis 11  
Statistical analysis description 
Family life: Week 11. The analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure, in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included terms for treatment, trial site, visit week, interaction term of treatment by visit week, and interaction term of baselinebyvisit.


Comparison groups 
Brexpiprazole (3mg) + ADT v Placebo +ADT


Number of subjects included in analysis 
444


Analysis specification 
Prespecified
