Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42517   clinical trials with a EudraCT protocol, of which   7000   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults with Major Depressive Disorder, the Polaris Trial.

    Summary
    EudraCT number
    2011-001349-33
    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

    Close Top of page
    Trial identification
    Sponsor protocol code
    331-10-227
    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., +1 240-683-3194, Mary.Hobart@otsuka-us.com
    Scientific contact
    Mary Hobart, Otsuka Pharmaceutical Development & Commercialization, Inc., +1 240-683-3194, Mary.Hobart@otsuka-us.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 OPC-34712 (1.0 and 3.0 milligrams (mg)/day) to placebo as adjunctive therapy to an assigned open-label antidepressant therapy (ADT) in participants who demonstrated an incomplete response after 8 weeks of prospective treatment with the same assigned open-label 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 sponsor-provided 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 follow-up 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 (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    676
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    Close Top of page
    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.

    Pre-assignment
    Screening details
    The study consisted of a 7 to 28-day Screening period, an 8-Week single-blind placebo + ADT prospective Phase-A, a 6-Week double-blind randomization Phase-B or single-blind Phase A+ for those participants who did not meet criteria for randomization and a Follow-up 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 double-blind 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 (anti-depressant therapy).
    Arm type
    Experimental

    Investigational medicinal product name
    Brexpiprazole
    Investigational medicinal product code
    Other name
    OPC-34712
    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 open-label ADT.
    Arm type
    Experimental

    Investigational medicinal product name
    Brexpiprazole
    Investigational medicinal product code
    Other name
    OPC-34712
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label 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.

    Number of subjects in period 1
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Started
    226
    230
    221
    Completed
    216
    210
    208
    Not completed
    10
    20
    13
         Protocol deviation
    1
    4
    1
         Physician decision
    -
    -
    1
         Met withdrawal criteria
    -
    2
    1
         Adverse event
    3
    9
    3
         Lack of efficacy
    1
    -
    -
         Consent withdrawn by subject
    4
    4
    7
         Lost to follow-up
    1
    1
    -

    Baseline characteristics

    Close Top of page
    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 (anti-depressant therapy).

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

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

    Reporting group values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT Total
    Number of subjects
    226 230 221 677
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    225 230 221 676
        From 65-84 years
    1 0 0 1
        85 years and over
    0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    45.7 ± 11.6 44.5 ± 11.2 46.6 ± 11 -
    Gender categorical
    Units: Subjects
        Female
    158 156 146 460
        Male
    68 74 75 217

    End points

    Close Top of page
    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 (anti-depressant therapy).

    Reporting group title
    Brexpiprazole (3mg) + ADT
    Reporting group description
    Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label 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
    Intention-to-treat
    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 Montgomery-Asberg 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.

    Primary: Mean change from the end of Phase A (Week 8 visit) to Phase B (Week 14 visit) in the Montgomery-Asberg Depression Rating Scale for the Efficacy Sample Set

    Close Top of page
    End point title
    Mean change from the end of Phase A (Week 8 visit) to Phase B (Week 14 visit) in the Montgomery-Asberg 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    225
    226
    218
    Units: Units on a scale
        least squares mean (standard error)
    -7.65 ± 0.5
    -7.98 ± 0.51
    -6.45 ± 0.51
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0925
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0327
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.92
         upper limit
    -0.13

    Primary: Mean Change in MADRS Total Score from Baseline End of Week 8 to Week 14 for the Efficacy Sample per final protocol

    Close Top of page
    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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    211
    213
    203
    Units: Units on a scale
        least squares mean (standard error)
    -7.64 ± 0.52
    -8.29 ± 0.53
    -6.33 ± 0.53
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0737
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0079
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.95
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.39
         upper limit
    -0.51

    Secondary: 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

    Close Top of page
    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 self-rated 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    225
    226
    218
    Units: Units on a scale
    least squares mean (standard error)
        Week 11
    -1.13 ± 0.13
    -0.67 ± 0.13
    -0.58 ± 0.11
        Week 14
    -1.33 ± 0.14
    -1.21 ± 0.13
    -0.84 ± 0.13
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0091
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.49
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0474
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.37
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0008
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.55
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5792
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.41
         upper limit
    0.23

    Secondary: 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

    Close Top of page
    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 self-rated 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    211
    213
    203
    Units: Units on a scale
    least squares mean (standard error)
        Week 11
    -1.11 ± 0.13
    -0.74 ± 0.13
    -0.53 ± 0.14
        Week 14
    -1.27 ± 0.15
    -1.26 ± 0.15
    -0.78 ± 0.15
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0158
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.49
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0191
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.48
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0015
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.58
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2627
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.56
         upper limit
    0.15

    Secondary: 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

    Close Top of page
    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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    225
    226
    218
    Units: Units on a scale
    least squares mean (standard error)
        Week 9 (N= 222, 221, 214)
    -3.25 ± 0.3
    -2.53 ± 0.3
    -2.19 ± 0.31
        Week 10 (N= 222, 221, 213)
    -5.34 ± 0.38
    -4.8 ± 0.38
    -3.91 ± 0.39
        Week 11 (N= 221, 218, 213)
    -6.25 ± 0.41
    -5.56 ± 0.41
    -4.85 ± 0.41
        Week 12 (N= 216, 213, 210)
    -7.08 ± 0.43
    -6.8 ± 0.44
    -5.52 ± 0.44
        Week 13 (N= 213, 212, 204)
    -7.55 ± 0.46
    -7.73 ± 0.46
    -6.02 ± 0.47
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0096
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.06
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4137
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.33
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0065
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.44
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0914 [1]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.89
    Confidence interval
         level
    95%
         sides
    2-sided
         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 group-by-visit and Baseline-by-visit 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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0139
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.39
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2097
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.71
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0099
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.56
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.034
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.29
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0177
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.53
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0085
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.98
         upper limit
    -0.44

    Secondary: 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

    Close Top of page
    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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    211
    213
    203
    Units: Units on a scale
    least squares mean (standard error)
        Week 9 (N=208, 210, 199)
    -3.09 ± 0.31
    -2.6 ± 0.31
    -2.18 ± 0.32
        Week 10 (N=208, 208, 199)
    -5.12 ± 0.39
    -4.92 ± 0.39
    -3.95 ± 0.4
        Week 11 (N=207, 205, 199)
    -6.22 ± 0.42
    -5.76 ± 0.43
    -4.86 ± 0.43
        Week 12 (N=203, 202, 195)
    -7.09 ± 0.45
    -7.11 ± 0.45
    -5.48 ± 0.46
        Week 13 (N=200, 199, 191)
    -7.56 ± 0.47
    -8.05 ± 0.48
    -5.93 ± 0.49
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0286
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.92
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3173
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.42
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0313
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.17
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0732
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.97
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0206
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.36
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1233
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.91
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0097
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.61
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0092
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.63
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0139
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.63
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0015
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.42
         upper limit
    -0.81

    Secondary: 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 (CGI-S) for the Efficacy Sample Set

    Close Top of page
    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 (CGI-S) for the Efficacy Sample Set
    End point description
    The severity of illness for each participant was rated using the CGI-S. 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    225
    226
    218
    Units: Units on a scale
    least squares mean (standard error)
        Week 9 (N= 222, 221, 214)
    -0.25 ± 0.03
    -0.22 ± 0.03
    -0.16 ± 0.03
        Week 10 (N= 222, 221, 213)
    -0.52 ± 0.05
    -0.46 ± 0.05
    -0.31 ± 0.05
        Week 11 (N= 221, 218, 213)
    -0.64 ± 0.05
    -0.51 ± 0.05
    -0.44 ± 0.05
        Week 12 (N= 216, 213, 210)
    -0.73 ± 0.05
    -0.72 ± 0.05
    -0.59 ± 0.05
        Week 13 (N= 213, 212, 204)
    -0.78 ± 0.06
    -0.77 ± 0.06
    -0.66 ± 0.06
        Week 14 (N= 216, 208, 207)
    -0.86 ± 0.06
    -0.9 ± 0.06
    -0.75 ± 0.06
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0436
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1741
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.06
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0012
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.21
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0266
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0034
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3053
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0541
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.15
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0912
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1553
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.12
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1855
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2015
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0852
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.32
         upper limit
    0.02

    Secondary: Mean change from end of Phase A (Week 8 visit) to every study week visit in Phase B Week in Clinical CGI-S for the Efficacy Sample per final protocol

    Close Top of page
    End point title
    Mean change from end of Phase A (Week 8 visit) to every study week visit in Phase B Week in Clinical CGI-S for the Efficacy Sample per final protocol
    End point description
    The severity of illness for each participant was rated using the CGI-S. 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    211
    213
    203
    Units: Units on a scale
    least squares mean (standard error)
        Week 9 (N=208, 210,199)
    -0.24 ± 0.03
    -0.23 ± 0.03
    -0.16 ± 0.03
        Week 10 (N=208, 208, 199)
    -0.5 ± 0.05
    -0.47 ± 0.05
    -0.33 ± 0.05
        Week 11 (N=207, 205, 199)
    -0.64 ± 0.05
    -0.53 ± 0.05
    -0.45 ± 0.05
        Week 12 (N=203, 202, 195)
    -0.73 ± 0.06
    -0.74 ± 0.06
    -0.58 ± 0.06
        Week 13 (N=200, 199, 191)
    -0.77 ± 0.06
    -0.8 ± 0.06
    -0.64 ± 0.06
        Week 14 (N=204, 196, 193)
    -0.87 ± 0.06
    -0.92 ± 0.06
    -0.72 ± 0.06
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0817
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1406
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.011
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.17
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0287
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0071
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.19
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2503
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0539
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.15
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0398
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.16
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1168
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0621
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.16
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.089
    Method
    Mixed models analysis
    Parameter type
    Median difference (final values)
    Point estimate
    -0.15
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0213
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.38
         upper limit
    -0.03

    Secondary: Mean change from end of Phase A (Week 8 visit) for every study week visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set

    Close Top of page
    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 (Self-Report) IDS-SR Total Score for the Efficacy Sample Set
    End point description
    IDS-SR was a 30-item self-report measured to assess core diagnostic depressive symptoms and atypical and melancholic symptom features of major depressive disorders. The IDS-SR 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 sub-items 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 sub-items were not included in the calculation of the total score. The IDS-SR Total Score was the sum of ratings of 28 item scores. The possible IDSSR Total Score ranged from 0 to 84. The IDS-SR Total Score was un-evaluable 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 IDS-SR 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    225
    226
    218
    Units: Units on a scale
    least squares mean (standard error)
        Week 9 (N= 222, 221, 214)
    -3.58 ± 0.41
    -2.68 ± 0.42
    -2.31 ± 0.42
        Week 10 (N= 222, 221, 213)
    -4.97 ± 0.49
    -4 ± 0.5
    -3.11 ± 0.5
        Week 11 (N= 220, 218, 213)
    -5.83 ± 0.56
    -4.15 ± 0.56
    -3.74 ± 0.57
        Week 12 (N= 216, 213, 210)
    -6.33 ± 0.59
    -5.77 ± 0.59
    -4.43 ± 0.6
        Week 13 (N= 213, 212, 204)
    -6.96 ± 0.63
    -6.62 ± 0.63
    -5.66 ± 0.64
        Week 14 (N= 216, 208, 207)
    -7.02 ± 0.66
    -6.94 ± 0.66
    -5.42 ± 0.67
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0228
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.28
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5081
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.37
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0064
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.86
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1898
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.89
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0074
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.09
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5935
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.42
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0211
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.9
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1031
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.34
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1366
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2709
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.96
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0812
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.33
         upper limit
    0.29

    Secondary: Mean change from end of Phase A (Week 8 visit) for every study week visit in Phase B in IDS-SR Total Score for the Efficacy Sample per final protocol

    Close Top of page
    End point title
    Mean change from end of Phase A (Week 8 visit) for every study week visit in Phase B in IDS-SR Total Score for the Efficacy Sample per final protocol
    End point description
    The IDS-SR was a 30-item self-report measured to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorders. The IDS-SR 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 sub-items 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 sub-items were not included in the calculation of the total score. The IDS-SR Total Score was the sum of ratings of 28 item scores. The possible IDSSR Total Score ranged from 0 to 84. The IDS-SR Total Score was un-evaluable 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 IDS-SR 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    211
    213
    203
    Units: Units on a scale
    least squares mean (standard error)
        Week 9 (N=208, 210, 199)
    -3.27 ± 0.42
    -2.65 ± 0.42
    -2.15 ± 0.43
        Week 10 (N=208, 209, 199)
    -4.7 ± 0.51
    -4.13 ± 0.51
    -2.94 ± 0.52
        Week 11 (N=206, 205, 199)
    -5.77 ± 0.57
    -4.29 ± 0.58
    -3.46 ± 0.59
        Week 12 (N=203, 202, 195)
    -6.33 ± 0.61
    -6.05 ± 0.61
    -4.18 ± 0.63
        Week 13 (N=200, 199, 191)
    -6.88 ± 0.64
    -6.97 ± 0.64
    -5.25 ± 0.66
        Week 14 (N=204, 196, 193)
    -6.97 ± 0.67
    -7.2 ± 0.68
    -5.07 ± 0.69
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0496
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.12
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.387
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.49
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0125
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.75
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0898
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.31
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.301 [2]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.83
    Confidence interval
         level
    95%
         sides
    2-sided
         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 group-by-visit and Baseline-by-visit 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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0118
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.15
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0287
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.87
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0686
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.63
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.056
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.72
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    414
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0448
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.9
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0251
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.98
         upper limit
    -0.27

    Secondary: 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

    Close Top of page
    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 HAM-D17 was utilized as a secondary assessment of a participants level of depression. The HAM-D (17-Item) 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    222
    220
    213
    Units: Units on a scale
        least squares mean (standard error)
    -5.47 ± 0.36
    -6.14 ± 0.36
    -4.8 ± 0.37
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1732 [3]
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.67
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0066 [4]
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.34
    Confidence interval
         level
    95%
         sides
    2-sided
         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

    Secondary: Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in HAM-D17 Total Score for the Efficacy Sample Set per final protocol

    Close Top of page
    End point title
    Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in HAM-D17 Total Score for the Efficacy Sample Set per final protocol
    End point description
    The HAM-D17 was utilized as a secondary assessment of a participants level of depression. The HAM-D (17-Item) 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    208
    207
    198
    Units: Units on a scale
        least squares mean (standard error)
    -5.36 ± 0.37
    -6.26 ± 0.38
    -4.57 ± 0.39
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1226 [5]
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.78
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [6]
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.69
    Confidence interval
         level
    95%
         sides
    2-sided
         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

    Secondary: Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in Hamilton Anxiety Rating Scale (HAM-A) Total Score for the Efficacy Sample Set

    Close Top of page
    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 (HAM-A) Total Score for the Efficacy Sample Set
    End point description
    The HAM-A is utilized for the evaluation of anxiety symptoms. The HAM-A 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 HAM-A 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    220
    216
    210
    Units: Units on a scale
        least squares mean (standard error)
    -3.43 ± 0.31
    -3.89 ± 0.31
    -3.33 ± 0.32
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8164 [7]
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1939 [8]
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.55
    Confidence interval
         level
    95%
         sides
    2-sided
         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

    Secondary: Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in HAM-A Total for the Efficacy Sample per final protocol

    Close Top of page
    End point title
    Mean change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in HAM-A Total for the Efficacy Sample per final protocol
    End point description
    The HAM-A is utilized for the evaluation of anxiety symptoms. The HAM-A 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 HAM-A 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    206
    204
    195
    Units: Units on a scale
        least squares mean (standard error)
    -3.35 ± 0.32
    -3.96 ± 0.33
    -3.07 ± 0.33
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5192 [9]
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.28
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0443 [10]
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.88
    Confidence interval
         level
    95%
         sides
    2-sided
         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

    Secondary: Mean CGI-I Score at each trial week visit in Phase B for the Efficacy Sample Set

    Close Top of page
    End point title
    Mean CGI-I 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 CGI-I. 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    225
    226
    218
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Week 9 (N= 222, 221, 214)
    3.36 ± 0.68
    3.4 ± 0.75
    3.51 ± 0.67
        Week 10 (N= 225, 226, 218)
    3.08 ± 0.85
    3.09 ± 0.85
    3.34 ± 0.85
        Week 11 (N= 225, 226, 218)
    2.91 ± 0.82
    2.99 ± 0.89
    3.17 ± 0.88
        Week 12 (N= 225, 226, 218)
    2.78 ± 0.87
    2.81 ± 0.95
    3.02 ± 0.95
        Week 13 (N= 225, 226, 218)
    2.72 ± 0.87
    2.73 ± 1.01
    2.97 ± 1
        Week 14 (N= 225, 226, 218)
    2.69 ± 0.89
    2.66 ± 1.1
    2.85 ± 1.01
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0248 [11]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.26
         upper limit
    -0.02
    Notes
    [11] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1334 [12]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.22
         upper limit
    0.03
    Notes
    [12] - P-value 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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0009 [13]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.42
         upper limit
    -0.11
    Notes
    [13] - P-value 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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0019 [14]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.38
         upper limit
    -0.09
    Notes
    [14] - P-value 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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0009 [15]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.42
         upper limit
    -0.11
    Notes
    [15] - P-value 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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0254 [16]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.34
         upper limit
    -0.02
    Notes
    [16] - P-value 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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0035 [17]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.41
         upper limit
    -0.08
    Notes
    [17] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0152 [18]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.39
         upper limit
    -0.04
    Notes
    [18] - P-value 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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004 [19]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.42
         upper limit
    -0.08
    Notes
    [19] - P-value 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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.013 [20]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.42
         upper limit
    -0.05
    Notes
    [20] - P-value 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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0755 [21]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.33
         upper limit
    0.02
    Notes
    [21] - P-value 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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0527 [22]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.39
         upper limit
    0
    Notes
    [22] - P-value and treatment difference (CI) are derived from CMH row mean scores statistics controlling for study center

    Secondary: Mean CGI-I Score at each trial week visit in Phase B for the Efficacy Sample per final protocol

    Close Top of page
    End point title
    Mean CGI-I 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 CGI-I. 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    211
    213
    203
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Week 9 (N=208, 210, 199)
    3.39 ± 0.65
    3.42 ± 0.74
    3.54 ± 0.65
        Week 10 (N=211, 213, 203)
    3.1 ± 0.82
    3.08 ± 0.84
    3.35 ± 0.84
        Week 11 (N=211, 213, 203)
    2.93 ± 0.8
    2.99 ± 0.89
    3.19 ± 0.86
        Week 12 (N=211, 213, 203)
    2.8 ± 0.86
    2.81 ± 0.94
    3.06 ± 0.94
        Week 13 (N=211, 213, 203)
    2.75 ± 0.86
    2.72 ± 1
    3.01 ± 0.96
        Week 14 (N=211, 213, 203)
    2.71 ± 0.88
    2.65 ± 1.09
    2.9 ± 0.99
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0275 [23]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.26
         upper limit
    -0.01
    Notes
    [23] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1583 [24]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.22
         upper limit
    0.04
    Notes
    [24] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0021 [25]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.41
         upper limit
    -0.09
    Notes
    [25] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0018 [26]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    -0.09
    Notes
    [26] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0011 [27]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.43
         upper limit
    -0.11
    Notes
    [27] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0021 [28]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.44
         upper limit
    -0.1
    Notes
    [28] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0111 [29]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.42
         upper limit
    -0.05
    Notes
    [29] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0046 [30]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.28
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.47
         upper limit
    -0.09
    Notes
    [30] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0237 [31]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.39
         upper limit
    -0.03
    Notes
    [31] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0171 [32]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.45
         upper limit
    -0.04
    Notes
    [32] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0235 [33]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.36
         upper limit
    -0.03
    Notes
    [33] - P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (CMH) row mean scores statistics controlling for study center.

    Secondary: 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.

    Close Top of page
    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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    222
    221
    214
    Units: Percentage of participants
    number (not applicable)
        Week 9 (N= 222, 221, 214)
    4.5
    0.45
    2.8
        Week 10 (N= 225, 226, 218)
    10.2
    6.19
    5.05
        Week 11 (N= 225, 226, 218)
    13.3
    10.6
    8.72
        Week 12 (N= 225, 226, 218)
    16.9
    15.5
    10.1
        Week 13 (N= 225, 226, 218)
    18.2
    18.6
    15.6
        Week 14 (N= 225, 226, 218)
    23.1
    22.1
    15.1
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5279
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.37
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0141
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0484
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    1.92
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5813
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.23
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1236
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.51
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4998
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.21
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0365
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.64
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0822
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.52
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4049
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2951
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.23
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0248
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.53
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0326
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.03
         upper limit
    2.21

    Secondary: 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

    Close Top of page
    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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    211
    213
    203
    Units: Percentage of participants
    number (not applicable)
        Week 9 (N=208, 210, 199)
    3.37
    0.48
    3.02
        Week 10 (N=211, 213, 203)
    7.58
    6.1
    4.93
        Week 11 (N=211, 213, 203)
    13.3
    11.3
    8.37
        Week 12 (N=211, 213, 203)
    16.6
    16.4
    10.3
        Week 13 (N=211, 213, 203)
    18
    19.2
    14.3
        Week 14 (N=211, 213, 203)
    23.2
    23
    14.3
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7993
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    0.87
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0118
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2825
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.6375
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0923
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.62
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3812
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.29
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0464
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.63
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.049
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Mean difference (final values)
    Point estimate
    1.62
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2124
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.32
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1078
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.41
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0094
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.69
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0162
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.09
         upper limit
    2.5

    Secondary: Percentage of participants with a MADRS Remission during Phase B relative to the end of Phase A (Week 8) for the Efficacy Sample Set.

    Close Top of page
    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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    222
    221
    214
    Units: Percentage of participants
    number (not applicable)
        Week 9 (N= 222, 221, 214)
    3.15
    0.45
    2.8
        Week 10 (N= 225, 226, 218)
    4
    2.65
    4.13
        Week 11 (N= 225, 226, 218)
    8.44
    6.19
    5.5
        Week 12 (N= 225, 226, 218)
    11.1
    8.85
    5.96
        Week 13 (N= 225, 226, 218)
    10.7
    12.8
    9.17
        Week 14 (N= 225, 226, 218)
    15.1
    13.7
    11.9
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.9498
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.03
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0141
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8609
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    0.93
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2846
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    0.59
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.248
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7513
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.13
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0554
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.82
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2409
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.48
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5538
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.18
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1743
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.44
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2843
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.464
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.74
         upper limit
    1.92

    Secondary: 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

    Close Top of page
    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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    211
    213
    203
    Units: Percentage of participants
    number (not applicable)
        Week 9 (N=208, 210, 199)
    1.92
    0.48
    3.02
        Week 10 (N=211, 213, 203)
    2.37
    2.82
    3.94
        Week 11 (N=211, 213, 203)
    8.06
    6.57
    5.42
        Week 12 (N=211, 213, 203)
    10.4
    9.39
    6.4
        Week 13 (N=211, 213, 203)
    9.95
    13.1
    8.37
        Week 14 (N=211, 213, 203)
    14.7
    14.1
    10.8
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3867
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0118
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.32
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    0.59
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3266
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3027
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.47
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.696
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.17
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1368
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.62
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2387
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.48
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4498
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.26
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1009
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1499
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.45
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3012
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of remission rate
    Point estimate
    1.31
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.78
         upper limit
    2.18

    Secondary: Percentage of participants with a CGI-I response during Phase B relative to the end of Phase A (Week 8 visit) for the Efficacy Sample Set

    Close Top of page
    End point title
    Percentage of participants with a CGI-I response during Phase B relative to the end of Phase A (Week 8 visit) for the Efficacy Sample Set
    End point description
    A CGI-I response was defined as a CGI-I 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    225
    226
    218
    Units: Percentage of participants
    number (not applicable)
        Week 9 (N= 222, 221, 214)
    9.46
    10.4
    6.54
        Week 10 (N= 225, 226, 218)
    23.6
    23
    13.3
        Week 11 (N= 225, 226, 218)
    28.4
    30.1
    21.6
        Week 12 (N= 225, 226, 218)
    35.1
    38.1
    29.4
        Week 13 (N= 225, 226, 218)
    40
    43.4
    28.9
        Week 14 (N= 225, 226, 218)
    41.8
    47.8
    36.7
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2873
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.41
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2677
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.37
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0031
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.8
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0066
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.7
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0665
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.34
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.025
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.41
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2224
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.18
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0369
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.31
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0179
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.36
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0011
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.49
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3249
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.12
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0122
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.06
         upper limit
    1.66

    Secondary: Percentage of participants with a CGI-I response during Phase B relative to the end of Phase A (Week 8 visit) for the Efficacy Sample per final protocol

    Close Top of page
    End point title
    Percentage of participants with a CGI-I 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 CGI-I response was defined as a CGI-I 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    211
    213
    203
    Units: Percentage of participants
    number (not applicable)
        Week 9 (N=208, 210, 199)
    7.69
    9.52
    5.53
        Week 10 (N=211, 213, 203)
    21.8
    23
    12.3
        Week 11 (N=211, 213, 203)
    27.5
    30
    19.7
        Week 12 (N=211, 213, 203)
    34.1
    38
    27.6
        Week 13 (N=211, 213, 203)
    38.9
    44.1
    27.1
        Week 14 (N=211, 213, 203)
    41.2
    48.4
    34
    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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5836
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.22
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3792
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.31
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0101
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.77
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0065
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.75
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0526
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.41
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0156
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.51
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1689
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.22
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0231
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.37
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0175
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0004
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.59
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1396
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.21
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0016
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Ratio of response rate
    Point estimate
    1.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.15
         upper limit
    1.86

    Secondary: Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set

    Close Top of page
    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 self-rated 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
    End point values
    Brexpiprazole (1mg) + ADT Brexpiprazole (3mg) + ADT Placebo +ADT
    Number of subjects analysed
    225
    226
    218
    Units: Units on a scale
    least squares mean (standard error)
        Work/school: Week 11
    -1 ± 0.16
    -0.18 ± 0.18
    -0.55 ± 0.15
        Work/school: Week 14
    -1.16 ± 0.17
    -0.91 ± 0.18
    -0.73 ± 0.17
        Social life: Week 11
    -1.13 ± 0.14
    -0.76 ± 0.14
    -0.72 ± 0.14
        Social life: Week 14
    -1.39 ± 0.15
    -1.31 ± 0.15
    -0.91 ± 0.15
        Family life: Week 11
    -1.14 ± 0.14
    -0.74 ± 0.14
    -0.51 ± 0.12
        Family life: Week 14
    -1.35 ± 0.15
    -1.28 ± 0.16
    -0.8 ± 0.15
    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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0377
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.45
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0741
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.43
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0966
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.37
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4774
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.18
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0263
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.41
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0214
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.48
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8281
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.054
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0008
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.63
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (1mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0093
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.55
    Confidence interval
         level
    95%
         sides
    2-sided
         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 baseline-by-visit.
    Comparison groups
    Brexpiprazole (3mg) + ADT v Placebo +ADT
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified