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    Clinical Trial Results:
    A Multicenter, Randomized, Double-Blind, Fixed-Dose, 6-Week Trial of the Efficacy and Safety of Asenapine Compared With Placebo Using Olanzapine as an Active Control in Subjects With an Acute Exacerbation of Schizophrenia (Phase 3B, Protocol P05688 [formerly 041038]).

    Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
    Summary
    EudraCT number
    		 2010-018407-28
    Trial protocol
    		 BG  
    Global end of trial date
    09 Sep 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Feb 2016
    First version publication date
    26 Feb 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    P05688
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01617187
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Merck Protocol number: MK-8274-001
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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
    09 Sep 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Sep 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this trial is to assess effect of asenapine 2.5 and 5 mg sublingually twice daily (BID) compared with placebo in treatment of schizophrenia (overall symptoms) as measured by the Positive and Negative Syndrome Scale (PANSS). Olanzapine administered 15 mg orally once daily (QD) was used as an active control. Primary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by change from Baseline in PANSS total score at Day 42. The first key secondary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by change from Baseline in Clinical Global Impression Scale-Severity (CGI-S) score at Day 42. The second key secondary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by rate of PANSS responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Dec 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 8 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Bulgaria: 53
    Country: Number of subjects enrolled
    Romania: 37
    Country: Number of subjects enrolled
    Russian Federation: 73
    Country: Number of subjects enrolled
    Ukraine: 38
    Country: Number of subjects enrolled
    United States: 140
    Country: Number of subjects enrolled
    Croatia: 19
    Worldwide total number of subjects
    360
    EEA total number of subjects
    109
    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)
    357
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 One participant randomized to asenapine 2.5 mg BID did not receive study drug but was recorded in clinical database as completing the study. In Subject Disposition table, this participant is presented as Not Completed in period "Randomization through Start Treatment" (Not Treated).

    Period 1
    Period 1 title
    Randomization through Start Treatment
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Asenapine 2.5 mg BID
    Arm description
    		 Participants were administered one 2.5 mg asenapine tablet BID for 42 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    Asenapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually

    Investigational medicinal product name
    Placebo Olanzapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

    Arm title
    		 Asenapine 5 mg BID
    Arm description
    		 Participants were administered one 5 mg asenapine tablet BID for 42 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    Asenapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually

    Investigational medicinal product name
    Placebo Olanzapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

    Arm title
    		 Olanzapine 15 mg QD
    Arm description
    		 Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Olanzapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 and 10 mg film-coated active olanzapine tablets administered orally QD. The time of the active olanzapine dose (either morning or evening) is not disclosed in order to preserve blinding

    Investigational medicinal product name
    Placebo Asenapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually

    Investigational medicinal product name
    Placebo Olanzapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

    Arm title
    		 Placebo BID
    Arm description
    		 Participants were administered placebo tablets BID for 42 days
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo Asenapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually

    Investigational medicinal product name
    Placebo Olanzapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

    Number of subjects in period 1
    		Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Started
    98
    113
    46
    103
    Completed
    97
    113
    46
    101
    Not completed
    1
    0
    0
    2
         Not Treated: Completed study in database
    1
    -
    -
    -
         Not Treated: Administrative Reason
    -
    -
    -
    1
         Not Treated: Adverse Event
    -
    -
    -
    1
    Period 2
    Period 2 title
    Treatment through Study Completion
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Asenapine 2.5 mg BID
    Arm description
    		 Participants were administered one 2.5 mg asenapine tablet BID for 42 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    Asenapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually

    Investigational medicinal product name
    Placebo Olanzapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

    Arm title
    		 Asenapine 5 mg BID
    Arm description
    		 Participants were administered one 5 mg asenapine tablet BID for 42 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    Asenapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually

    Investigational medicinal product name
    Placebo Olanzapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

    Arm title
    		 Olanzapine 15 mg QD
    Arm description
    		 Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Olanzapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 and 10 mg film-coated active olanzapine tablets administered orally QD. The time of the active olanzapine dose (either morning or evening) is not disclosed in order to preserve blinding

    Investigational medicinal product name
    Placebo Olanzapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

    Investigational medicinal product name
    Placebo Asenapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually

    Arm title
    		 Placebo BID
    Arm description
    		 Participants were administered placebo tablets BID for 42 days
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo Olanzapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

    Investigational medicinal product name
    Placebo Asenapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: The participants who started Period 1 are those randomized, 3 of whom did not receive study drug. The participants who started Period 2 are those who received study drug. The baseline demographics table presents data for participants treated, therefore Period 2 was set as the baseline period.
    Number of subjects in period 2 [2]
    		Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Started
    97
    113
    46
    101
    Completed
    86
    102
    41
    91
    Not completed
    11
    11
    5
    10
         Consent withdrawn by subject
    5
    8
    3
    6
         Adverse event, non-fatal
    1
    1
    -
    1
         Lost to follow-up
    4
    2
    2
    2
         Protocol deviation
    1
    -
    -
    1
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The worldwide number enrolled in the trial presents participants randomized; 3 of these participants did not receive study drug. The participants who started Period 2 ("baseline period") are those who received study drug. The baseline demographics table presents data for participants treated, therefore Period 2 was set as the baseline period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Asenapine 2.5 mg BID
    Reporting group description
    		 Participants were administered one 2.5 mg asenapine tablet BID for 42 days

    Reporting group title
    Asenapine 5 mg BID
    Reporting group description
    		 Participants were administered one 5 mg asenapine tablet BID for 42 days

    Reporting group title
    Olanzapine 15 mg QD
    Reporting group description
    		 Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered

    Reporting group title
    Placebo BID
    Reporting group description
    		 Participants were administered placebo tablets BID for 42 days

    Reporting group values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID Total
    Number of subjects
    		 97 113 46 101 357
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 41.5 ( 10.79 ) 39.1 ( 10.68 ) 40.8 ( 11.15 ) 41.4 ( 12.05 ) -
    Gender categorical
    Units: Subjects
        Female
    		 39 44 18 47 148
        Male
    		 58 69 28 54 209
    Positive and Negative Syndrome Scale (PANSS) total score
    The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score (30 items) ranged from 30 to 210 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (Full Analysis Set [FAS]): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 93.3 ( 11.1 ) 95.8 ( 13.77 ) 92.7 ( 10.47 ) 93.4 ( 11.16 ) -
    Clinical Global Impression Scale-Severity (CGI-S) score
    CGI-S is a 7-point scale for assessing the global severity of the participant’s illness, with ratings from 1=normal, not ill to 7=very severely ill. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 4.8 ( 0.64 ) 4.9 ( 0.64 ) 4.8 ( 0.61 ) 4.8 ( 0.61 ) -
    Body Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 81.6 ( 17.73 ) 78.6 ( 17.88 ) 80.7 ( 17.79 ) 77.1 ( 17.56 ) -
    PANSS negative subscale score
    The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS negative subscale score (7 PANSS items) ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 23.5 ( 4.47 ) 24.1 ( 4.5 ) 23.4 ( 3.96 ) 23.9 ( 4.22 ) -
    PANSS positive subscale score
    The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive subscale score (7 PANSS items) ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 24.4 ( 4.05 ) 25.5 ( 4.76 ) 24.6 ( 3.46 ) 24.6 ( 3.88 ) -
    PANSS general psychopathology subscale score
    The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS general psychopathology subscale score (16 PANSS items) ranged from 16 to 112 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 45.5 ( 6.05 ) 46.3 ( 6.87 ) 44.7 ( 6.2 ) 44.9 ( 6.05 ) -
    PANSS Marder factor positive symptom score
    The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder factor positive symptom score (calculated from value of 8 identified PANSS items) ranged from 8 to 56 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 29.3 ( 5.02 ) 30 ( 5.05 ) 29 ( 4.69 ) 29.4 ( 4.36 ) -
    PANSS Marder factor negative symptom score
    The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder factor negative symptom score (calculated from value of 7 identified PANSS items) ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 22.6 ( 4.3 ) 23 ( 4.66 ) 23 ( 4.44 ) 22.8 ( 4.76 ) -
    PANSS Marder factor disorganized thought symptom score
    The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder factor disorganized thought symptom score (calculated from value of 7 identified PANSS items) ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 21.5 ( 4.32 ) 22.6 ( 4.93 ) 21.2 ( 4.29 ) 21.6 ( 4.42 ) -
    PANSS Marder factor hostility/excitement symptom score
    The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder factor hostility/excitement symptom score (calculated from value of 4 identified PANSS items) ranged from 4 to 28 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 9 ( 2.99 ) 9.4 ( 3.49 ) 8.7 ( 3.11 ) 8.8 ( 3.22 ) -
    PANSS Marder factor anxiety/depression symptom score
    The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder factor anxiety/depression symptom score (calculated from value of 4 identified PANSS items) ranged from 4 to 28 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 11 ( 2.97 ) 10.9 ( 3.13 ) 10.9 ( 3.62 ) 10.7 ( 2.96 ) -

    End points

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    End points reporting groups
    Reporting group title
    Asenapine 2.5 mg BID
    Reporting group description
    		 Participants were administered one 2.5 mg asenapine tablet BID for 42 days

    Reporting group title
    Asenapine 5 mg BID
    Reporting group description
    		 Participants were administered one 5 mg asenapine tablet BID for 42 days

    Reporting group title
    Olanzapine 15 mg QD
    Reporting group description
    		 Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered

    Reporting group title
    Placebo BID
    Reporting group description
    		 Participants were administered placebo tablets BID for 42 days
    Reporting group title
    Asenapine 2.5 mg BID
    Reporting group description
    		 Participants were administered one 2.5 mg asenapine tablet BID for 42 days

    Reporting group title
    Asenapine 5 mg BID
    Reporting group description
    		 Participants were administered one 5 mg asenapine tablet BID for 42 days

    Reporting group title
    Olanzapine 15 mg QD
    Reporting group description
    		 Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered

    Reporting group title
    Placebo BID
    Reporting group description
    		 Participants were administered placebo tablets BID for 42 days

    Primary: Change From Baseline in PANSS Total Score at Day 42

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    End point title
    		 Change From Baseline in PANSS Total Score at Day 42
    End point description
    The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 42; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Primary
    End point timeframe
    Baseline and Day 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
        least squares mean (standard error)
    -17.4 ( 1.8 )
    -21.7 ( 1.6 )
    -21.6 ( 2.32 )
    -16.2 ( 1.71 )
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, Mixed Model Repeated Measures (MMRM) model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6043 [1]
    Method
    		 MMRM
    Parameter type
    		 Least Squares (LS) means difference
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.1
         upper limit
    		 3.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.46
    Notes
    [1] - Adjusted p-value from graphical approach to control Type 1 error rate among primary and secondary efficacy hypotheses
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0356 [2]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -5.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.1
         upper limit
    		 -1
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.32
    Notes
    [2] - Adjusted p-value from graphical approach to control Type 1 error rate among primary and secondary efficacy hypotheses
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0587 [3]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -5.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.1
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.86
    Notes
    [3] - Unadjusted p-value

    Secondary: Change From Baseline in CGI-S Score at Day 42

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    End point title
    		 Change From Baseline in CGI-S Score at Day 42
    End point description
    Change from baseline in CGI-S score at Day 42 is a Key Secondary Outcome Measure. CGI-S is a 7-point scale for assessing the global severity of the participant’s illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 42; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
        least squares mean (standard error)
    -0.9 ( 0.11 )
    -1.2 ( 0.1 )
    -1.1 ( 0.14 )
    -1 ( 0.11 )
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” below is sum of participants in FAS population in the 2 treatment groups compared and is automatically calculated by data entry system; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants. Confirmative testing of asenapine versus placebo was performed only if both asenapine doses were statistically superior to placebo in reduction from baseline in PANSS Total Score at Day 42.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9083 [4]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Notes
    [4] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” below is sum of participants in FAS population in the 2 treatment groups compared and is automatically calculated by data entry system; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants. Confirmative testing of asenapine versus placebo was performed only if both asenapine doses were statistically superior to placebo in reduction from baseline in PANSS Total Score at Day 42.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0601 [5]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [5] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3898 [6]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.18
    Notes
    [6] - Unadjusted p-value

    Secondary: Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42

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    End point title
    		 Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42
    End point description
    Rate of PANSS responders at Day 42 is a Key Secondary Outcome Measure. A PANSS responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS total score at a post-baseline assessment. The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. Missing data were imputed by Last Observation Carried Forward (LOCF). Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: percentage of participants
        number (not applicable)
    14.6
    25.2
    26.7
    19.2
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    Confirmative testing of asenapine versus placebo for this measure was to be performed only if both asenapine doses were statistically superior to placebo in reduction from baseline in PANSS Total Score at Day 42.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.37 [7]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [7] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    Confirmative testing of asenapine versus placebo for this measure was to be performed only if both asenapine doses were statistically superior to placebo in reduction from baseline in PANSS Total Score at Day 42.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1708 [8]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [8] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.262 [9]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [9] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

    Secondary: Change From Baseline in Body Weight at Day 42

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    End point title
    		 Change From Baseline in Body Weight at Day 42
    End point description
    Change from baseline in body weight at Day 42 is the Key Safety Outcome Measure. Population for this analysis was all randomized participants who received ≥1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    97
    113
    46
    101
    Units: kg
        least squares mean (standard error)
    1.3 ( 0.38 )
    1.3 ( 0.33 )
    2.4 ( 0.47 )
    0.3 ( 0.35 )
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the all subjects treated population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire all subjects treated population in all 4 treatment groups, which includes 357 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Olanzapine 15 mg QD
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0491 [10]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6
    Notes
    [10] - p-value adjusted for multiple comparisons using Hochberg's method
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the all subjects treated population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire all subjects treated population in all 4 treatment groups, which includes 357 participants.
    Comparison groups
    Asenapine 5 mg BID v Olanzapine 15 mg QD
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0491 [11]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.57
    Notes
    [11] - p-value adjusted for multiple comparisons using Hochberg's method
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the all subjects treated population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire all subjects treated population in all 4 treatment groups, which includes 357 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    198
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0567 [12]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.51
    Notes
    [12] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the all subjects treated population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire all subjects treated population in all 4 treatment groups, which includes 357 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0391 [13]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.48
    Notes
    [13] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the all subjects treated population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire all subjects treated population in all 4 treatment groups, which includes 357 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0003 [14]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 3.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.58
    Notes
    [14] - Unadjusted p-value

    Secondary: Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35

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    End point title
    		 Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35
    End point description
    The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 4, 7, 14, 21, 28 and 35
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
    least squares mean (standard error)
        Day 4
    -4 ( 0.8 )
    -4.9 ( 0.76 )
    -5.5 ( 1.15 )
    -4.8 ( 0.81 )
        Day 7
    -7.2 ( 1.17 )
    -9.1 ( 1.09 )
    -9.3 ( 1.67 )
    -7.1 ( 1.16 )
        Day 14
    -9.9 ( 1.31 )
    -12.5 ( 1.19 )
    -12.4 ( 1.8 )
    -10.7 ( 1.28 )
        Day 21
    -12 ( 1.55 )
    -14.8 ( 1.4 )
    -15.2 ( 2.09 )
    -13.2 ( 1.5 )
        Day 28
    -12.3 ( 1.69 )
    -17.1 ( 1.49 )
    -17.3 ( 2.21 )
    -15.5 ( 1.61 )
        Day 35
    -17 ( 1.66 )
    -19 ( 1.48 )
    -20.3 ( 2.19 )
    -15.4 ( 1.58 )
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4849 [15]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 2.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.09
    Notes
    [15] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8902 [16]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.06
    Notes
    [16] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5826 [17]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.36
    Notes
    [17] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9271 [18]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.61
    Notes
    [18] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1902 [19]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.1
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.56
    Notes
    [19] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.271 [20]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.2
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    2
    Notes
    [20] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6773 [21]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 4.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.79
    Notes
    [21] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2895 [22]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.2
         upper limit
    		 1.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.72
    Notes
    [22] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4261 [23]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6
         upper limit
    		 2.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.18
    Notes
    [23] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5505 [24]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 5.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.13
    Notes
    [24] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4286 [25]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.6
         upper limit
    		 2.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.03
    Notes
    [25] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4423 [26]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 3.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.56
    Notes
    [26] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1691 [27]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    3.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 7.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.3
    Notes
    [27] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4682 [28]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.8
         upper limit
    		 2.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.17
    Notes
    [28] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4961 [29]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.2
         upper limit
    		 3.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.71
    Notes
    [29] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4697 [30]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.1
         upper limit
    		 2.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.26
    Notes
    [30] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0947 [31]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.8
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.14
    Notes
    [31] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0675 [32]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -4.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.2
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.68
    Notes
    [32] - Unadjusted p-value

    Secondary: Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Days 4, 7, 14, 21, 28 and 35

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    End point title
    		 Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Days 4, 7, 14, 21, 28 and 35
    End point description
    A PANSS responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS total score at a post-baseline assessment. The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Days 4, 7, 14, 21, 28 and 35
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: percentage of participants
    number (not applicable)
        Day 4 (n = 95,108,44,97)
    0
    0
    0
    2.1
        Day 7 (n = 96,111,45,99)
    2.1
    5.4
    0
    5.1
        Day 14 (n = 96,111,45,99)
    5.2
    5.4
    4.4
    7.1
        Day 21 (n = 96,111,45,99)
    8.3
    14.4
    11.1
    13.1
        Day 28 (n = 96,111,45,99)
    10.4
    16.2
    15.6
    14.1
        Day 35 (n = 96,111,45,99)
    15.6
    21.6
    15.6
    17.2
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1736 [33]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [33] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1736 [34]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [34] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.285 [35]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [35] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.329 [36]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [36] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6938 [37]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [37] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1105 [38]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [38] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6804 [39]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [39] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9704 [40]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [40] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6604 [41]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [41] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2447 [42]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [42] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4834 [43]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [43] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9189 [44]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [44] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.437 [45]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [45] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2894 [46]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [46] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6953 [47]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [47] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4892 [48]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [48] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1954 [49]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [49] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.799 [50]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [50] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

    Secondary: Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35

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    End point title
    		 Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35
    End point description
    CGI-S is a 7-point scale for assessing the global severity of the participant’s illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 4, 7, 14, 21, 28 and 35
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
    least squares mean (standard error)
        Day 4
    -0.1 ( 0.05 )
    -0.2 ( 0.05 )
    -0.2 ( 0.07 )
    -0.2 ( 0.05 )
        Day 7
    -0.3 ( 0.07 )
    -0.3 ( 0.06 )
    -0.3 ( 0.1 )
    -0.3 ( 0.07 )
        Day 14
    -0.6 ( 0.08 )
    -0.6 ( 0.07 )
    -0.6 ( 0.11 )
    -0.5 ( 0.08 )
        Day 21
    -0.6 ( 0.1 )
    -0.8 ( 0.09 )
    -0.8 ( 0.13 )
    -0.7 ( 0.09 )
        Day 28
    -0.7 ( 0.11 )
    -0.9 ( 0.09 )
    -0.8 ( 0.14 )
    -0.8 ( 0.1 )
        Day 35
    -0.9 ( 0.11 )
    -1.1 ( 0.1 )
    -1 ( 0.14 )
    -0.8 ( 0.1 )
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4255 [51]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Notes
    [51] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9564 [52]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.06
    Notes
    [52] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6363 [53]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [53] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8759 [54]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [54] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9598 [55]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Notes
    [55] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9789 [56]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [56] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4671 [57]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Notes
    [57] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6359 [58]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Notes
    [58] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5454 [59]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [59] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4188 [60]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13
    Notes
    [60] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5318 [61]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13
    Notes
    [61] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5683 [62]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.16
    Notes
    [62] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2972 [63]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [63] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.482 [64]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13
    Notes
    [64] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9901 [65]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.17
    Notes
    [65] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6682 [66]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Notes
    [66] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1111 [67]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [67] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.24 [68]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.17
    Notes
    [68] - Unadjusted p-value

    Secondary: Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42

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    End point title
    		 Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42
    End point description
    A CGI-I responder was defined as a participant who had a CGI-I score of 1 (very much improved) or 2 (much improved) at a post-baseline assessment. CGI-I is a 7-point scale for assessing the global improvement of the participant’s illness relative to baseline, with ratings from 1=very much improved to 7=very much worse. Missing data were imputed by LOCF. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Days 4, 7, 14, 21, 28, 35 and 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: percentage of participants
    number (not applicable)
        Day 4 (n = 95,108,44,98)
    34.7
    33.3
    43.2
    37.8
        Day 7 (n = 96,111,45,99)
    51
    46.8
    60
    45.5
        Day 14 (n = 96,111,45,99)
    51
    60.4
    71.1
    54.5
        Day 21 (n = 96,111,45,99)
    54.2
    63.1
    75.6
    58.6
        Day 28 (n = 96,111,45,99)
    58.3
    62.2
    73.3
    60.6
        Day 35 (n = 96,111,45,99)
    60.4
    64
    82.2
    64.6
        Day 42 (n = 96,111,45,99)
    59.4
    66.7
    84.4
    62.6
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6205 [69]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [69] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4829 [70]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [70] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3945 [71]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [71] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4076 [72]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [72] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.969 [73]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [73] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.117 [74]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [74] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5088 [75]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [75] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3426 [76]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [76] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0762 [77]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [77] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5531 [78]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [78] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4875 [79]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [79] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0692 [80]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [80] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7482 [81]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [81] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8037 [82]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [82] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0859 [83]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [83] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.585 [84]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [84] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9698 [85]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [85] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0132 [86]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [86] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7129 [87]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [87] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5074 [88]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [88] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.004 [89]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [89] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

    Secondary: Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

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    End point title
    		 Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42
    End point description
    This measure reports results for the 7 items of the negative subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms. Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. PANSS negative subscale score for each participant was sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 4, 7, 14, 21, 28, 35 and 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
    least squares mean (standard error)
        Day 4
    -0.7 ( 0.29 )
    -0.5 ( 0.27 )
    -0.9 ( 0.42 )
    -0.8 ( 0.29 )
        Day 7
    -1.2 ( 0.33 )
    -1.3 ( 0.31 )
    -1.5 ( 0.47 )
    -1.1 ( 0.33 )
        Day 14
    -1.6 ( 0.37 )
    -2.3 ( 0.34 )
    -1.7 ( 0.51 )
    -1.8 ( 0.37 )
        Day 21
    -2.3 ( 0.41 )
    -2.5 ( 0.37 )
    -2 ( 0.56 )
    -2.3 ( 0.4 )
        Day 28
    -2.5 ( 0.45 )
    -3.1 ( 0.4 )
    -2.6 ( 0.59 )
    -3 ( 0.43 )
        Day 35
    -3.3 ( 0.48 )
    -3.4 ( 0.43 )
    -3.4 ( 0.63 )
    -2.6 ( 0.46 )
        Day 42
    -3.3 ( 0.54 )
    -4.3 ( 0.48 )
    -3.8 ( 0.68 )
    -3.2 ( 0.51 )
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8829 [90]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [90] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5488 [91]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.39
    Notes
    [91] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.783 [92]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5
    Notes
    [92] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.807 [93]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45
    Notes
    [93] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.528 [94]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.44
    Notes
    [94] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4025 [95]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.57
    Notes
    [95] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6471 [96]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 1.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.51
    Notes
    [96] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2504 [97]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Notes
    [97] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9223 [98]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.62
    Notes
    [98] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8839 [99]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.56
    Notes
    [99] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8077 [100]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [100] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6216 [101]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.68
    Notes
    [101] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4248 [102]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.61
    Notes
    [102] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7667 [103]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.58
    Notes
    [103] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6282 [104]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 1.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.72
    Notes
    [104] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.315 [105]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.65
    Notes
    [105] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1908 [106]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.61
    Notes
    [106] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3128 [107]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.77
    Notes
    [107] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8812 [108]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.73
    Notes
    [108] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1143 [109]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.69
    Notes
    [109] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4418 [110]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.84
    Notes
    [110] - Unadjusted p-value

    Secondary: Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

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    End point title
    		 Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42
    End point description
    This measure reports results for the 7 items of the positive subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms. Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. PANSS positive subscale score for each participant was sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 4, 7, 14, 21, 28, 35 and 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
    least squares mean (standard error)
        Day 4
    -1.2 ( 0.29 )
    -1.6 ( 0.28 )
    -2.3 ( 0.42 )
    -1.7 ( 0.3 )
        Day 7
    -2.3 ( 0.39 )
    -2.8 ( 0.36 )
    -3.6 ( 0.55 )
    -2.6 ( 0.38 )
        Day 14
    -3.4 ( 0.45 )
    -3.9 ( 0.4 )
    -4.4 ( 0.61 )
    -3.7 ( 0.43 )
        Day 21
    -4 ( 0.52 )
    -5 ( 0.47 )
    -5.7 ( 0.7 )
    -4.5 ( 0.51 )
        Day 28
    -4.1 ( 0.59 )
    -5.7 ( 0.52 )
    -6.2 ( 0.77 )
    -5 ( 0.56 )
        Day 35
    -5.2 ( 0.6 )
    -6.3 ( 0.53 )
    -6.8 ( 0.78 )
    -5.5 ( 0.57 )
        Day 42
    -5.6 ( 0.65 )
    -7.2 ( 0.57 )
    -7.5 ( 0.83 )
    -5.4 ( 0.61 )
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.216 [111]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [111] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9494 [112]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.39
    Notes
    [112] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1834 [113]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5
    Notes
    [113] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6347 [114]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Notes
    [114] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6917 [115]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.51
    Notes
    [115] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1431 [116]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66
    Notes
    [116] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6267 [117]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 1.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.61
    Notes
    [117] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.726 [118]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.58
    Notes
    [118] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3326 [119]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.74
    Notes
    [119] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4575 [120]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.72
    Notes
    [120] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.493 [121]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.68
    Notes
    [121] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1886 [122]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.86
    Notes
    [122] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2643 [123]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 2.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.8
    Notes
    [123] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3516 [124]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.76
    Notes
    [124] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2068 [125]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.94
    Notes
    [125] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7284 [126]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.82
    Notes
    [126] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2698 [127]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.77
    Notes
    [127] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.151 [128]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.96
    Notes
    [128] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8039 [129]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 1.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.88
    Notes
    [129] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0306 [130]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.5
         upper limit
    		 -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.83
    Notes
    [130] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0406 [131]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.1
         upper limit
    		 -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.03
    Notes
    [131] - Unadjusted p-value

    Secondary: Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

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    End point title
    		 Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42
    End point description
    This measure reports results for the 16 items of the general psychopathology subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS general psychopathology subscale score for each participant was calculated as the sum of the rating assigned to each of the 16 subscale items, and ranged from 16 to 112 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 4, 7, 14, 21, 28, 35 and 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
    least squares mean (standard error)
        Day 4
    -2.2 ( 0.49 )
    -2.7 ( 0.46 )
    -2.5 ( 0.7 )
    -2.4 ( 0.49 )
        Day 7
    -3.8 ( 0.69 )
    -4.9 ( 0.64 )
    -4.4 ( 0.98 )
    -3.6 ( 0.68 )
        Day 14
    -5.1 ( 0.73 )
    -6.2 ( 0.66 )
    -6.4 ( 1 )
    -5.4 ( 0.71 )
        Day 21
    -5.9 ( 0.84 )
    -7.4 ( 0.76 )
    -7.7 ( 1.13 )
    -6.7 ( 0.81 )
        Day 28
    -5.9 ( 0.93 )
    -8.2 ( 0.82 )
    -8.6 ( 1.21 )
    -7.7 ( 0.88 )
        Day 35
    -8.8 ( 0.88 )
    -9.2 ( 0.79 )
    -10.2 ( 1.16 )
    -7.6 ( 0.84 )
        Day 42
    -8.9 ( 0.97 )
    -10.1 ( 0.86 )
    -10.4 ( 1.23 )
    -8 ( 0.92 )
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7819 [132]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 1.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66
    Notes
    [132] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.703 [133]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.65
    Notes
    [133] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.952 [134]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.7
         upper limit
    		 1.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.83
    Notes
    [134] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7907 [135]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 1.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.95
    Notes
    [135] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1391 [136]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.91
    Notes
    [136] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4901 [137]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 1.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.18
    Notes
    [137] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8079 [138]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.7
         upper limit
    		 2.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    1
    Notes
    [138] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3889 [139]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.95
    Notes
    [139] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3907 [140]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.21
    Notes
    [140] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5363 [141]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.15
    Notes
    [141] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5075 [142]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.09
    Notes
    [142] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4526 [143]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.7
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.38
    Notes
    [143] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1548 [144]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 4.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.26
    Notes
    [144] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6589 [145]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 1.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.19
    Notes
    [145] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5171 [146]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.9
         upper limit
    		 2
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.48
    Notes
    [146] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3133 [147]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.6
         upper limit
    		 1.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.2
    Notes
    [147] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1723 [148]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.8
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.13
    Notes
    [148] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0663 [149]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.42
    Notes
    [149] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5128 [150]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.5
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.32
    Notes
    [150] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0842 [151]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.24
    Notes
    [151] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1217 [152]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.52
    Notes
    [152] - Unadjusted p-value

    Secondary: Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

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    End point title
    		 Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
    End point description
    This measure reports results for the 8 items of the Marder positive symptom factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. PANSS Marder factor positive symptom score for each participant was sum of rating assigned to each of the 8 applicable Marder factor items, and ranged from 8 to 56 with a higher score indicating greater severity of symptoms. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 4, 7, 14, 21, 28, 35 and 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
    least squares mean (standard error)
        Day 4
    -1.3 ( 0.29 )
    -1.8 ( 0.27 )
    -2 ( 0.41 )
    -2 ( 0.29 )
        Day 7
    -2.5 ( 0.41 )
    -2.9 ( 0.38 )
    -3.2 ( 0.58 )
    -2.8 ( 0.4 )
        Day 14
    -3.9 ( 0.49 )
    -4 ( 0.44 )
    -4.4 ( 0.67 )
    -4.1 ( 0.47 )
        Day 21
    -4.5 ( 0.55 )
    -5.4 ( 0.5 )
    -5.5 ( 0.74 )
    -5.1 ( 0.54 )
        Day 28
    -4.8 ( 0.6 )
    -6.3 ( 0.53 )
    -6.6 ( 0.78 )
    -5.6 ( 0.57 )
        Day 35
    -6.1 ( 0.64 )
    -6.7 ( 0.57 )
    -6.9 ( 0.84 )
    -6.1 ( 0.61 )
        Day 42
    -6.8 ( 0.67 )
    -7.6 ( 0.59 )
    -7.8 ( 0.86 )
    -6.2 ( 0.63 )
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0584 [153]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 1.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.39
    Notes
    [153] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5197 [154]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.38
    Notes
    [154] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9693 [155]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Notes
    [155] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6161 [156]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.56
    Notes
    [156] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.788 [157]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [157] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5526 [158]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7
    Notes
    [158] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7647 [159]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 1.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.67
    Notes
    [159] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.89 [160]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.64
    Notes
    [160] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7097 [161]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.81
    Notes
    [161] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4601 [162]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 2.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.76
    Notes
    [162] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6288 [163]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.72
    Notes
    [163] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6099 [164]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.91
    Notes
    [164] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.279 [165]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 2.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.82
    Notes
    [165] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4253 [166]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.77
    Notes
    [166] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3014 [167]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.96
    Notes
    [167] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.972 [168]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.7
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.87
    Notes
    [168] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4758 [169]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.82
    Notes
    [169] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4419 [170]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 1.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.03
    Notes
    [170] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4762 [171]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.91
    Notes
    [171] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1046 [172]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.86
    Notes
    [172] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1411 [173]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.7
         upper limit
    		 0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.06
    Notes
    [173] - Unadjusted p-value

    Secondary: Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

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    End point title
    		 Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
    End point description
    This measure reports results for the 7 items of the Marder negative symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. PANSS Marder factor negative symptom score for each participant was sum of the rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 4, 7, 14, 21, 28, 35 and 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
    least squares mean (standard error)
        Day 4
    -1.2 ( 0.3 )
    -0.8 ( 0.28 )
    -0.8 ( 0.43 )
    -0.7 ( 0.3 )
        Day 7
    -1.7 ( 0.37 )
    -1.9 ( 0.34 )
    -1.8 ( 0.53 )
    -1.3 ( 0.37 )
        Day 14
    -2 ( 0.41 )
    -2.8 ( 0.37 )
    -2.2 ( 0.56 )
    -2 ( 0.4 )
        Day 21
    -2.6 ( 0.44 )
    -3.2 ( 0.4 )
    -2.6 ( 0.6 )
    -2.5 ( 0.43 )
        Day 28
    -2.9 ( 0.51 )
    -3.8 ( 0.45 )
    -3.2 ( 0.67 )
    -3.5 ( 0.49 )
        Day 35
    -3.5 ( 0.52 )
    -3.9 ( 0.46 )
    -4.1 ( 0.68 )
    -3 ( 0.49 )
        Day 42
    -3.4 ( 0.53 )
    -4.7 ( 0.47 )
    -4.3 ( 0.67 )
    -4 ( 0.51 )
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2754 [174]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [174] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.85 [175]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.39
    Notes
    [175] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8439 [176]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.51
    Notes
    [176] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4741 [177]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.51
    Notes
    [177] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2158 [178]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Notes
    [178] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.506 [179]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.7
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.63
    Notes
    [179] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9956 [180]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.56
    Notes
    [180] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1624 [181]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Notes
    [181] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7662 [182]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.68
    Notes
    [182] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8363 [183]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.61
    Notes
    [183] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2388 [184]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.58
    Notes
    [184] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9435 [185]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.73
    Notes
    [185] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4267 [186]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7
    Notes
    [186] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.681 [187]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.65
    Notes
    [187] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7673 [188]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.82
    Notes
    [188] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.483 [189]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7
    Notes
    [189] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2128 [190]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66
    Notes
    [190] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1756 [191]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.83
    Notes
    [191] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4246 [192]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.72
    Notes
    [192] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2873 [193]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.68
    Notes
    [193] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7308 [194]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.83
    Notes
    [194] - Unadjusted p-value

    Secondary: Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

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    End point title
    		 Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
    End point description
    This measure reports results for the 7 items of the Marder disorganized thoughts factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. PANSS Marder factor disorganized thought symptom score for each participant was sum of rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 4, 7, 14, 21, 28, 35 and 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
    least squares mean (standard error)
        Day 4
    -0.3 ( 0.24 )
    -0.7 ( 0.22 )
    -1.1 ( 0.34 )
    -0.7 ( 0.24 )
        Day 7
    -1 ( 0.32 )
    -1.4 ( 0.29 )
    -1.6 ( 0.45 )
    -0.7 ( 0.31 )
        Day 14
    -1.3 ( 0.36 )
    -2 ( 0.33 )
    -2.2 ( 0.49 )
    -1.5 ( 0.35 )
        Day 21
    -2.3 ( 0.41 )
    -2.5 ( 0.37 )
    -2.7 ( 0.54 )
    -2.1 ( 0.39 )
        Day 28
    -2.4 ( 0.42 )
    -3.1 ( 0.37 )
    -3.1 ( 0.54 )
    -2.4 ( 0.4 )
        Day 35
    -3.5 ( 0.43 )
    -3.5 ( 0.38 )
    -4.3 ( 0.56 )
    -2.4 ( 0.41 )
        Day 42
    -3.8 ( 0.45 )
    -4.3 ( 0.4 )
    -4.7 ( 0.58 )
    -2.7 ( 0.43 )
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2116 [195]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32
    Notes
    [195] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9039 [196]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.31
    Notes
    [196] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2959 [197]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [197] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5909 [198]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.44
    Notes
    [198] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1489 [199]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Notes
    [199] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1 [200]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [200] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.783 [201]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Notes
    [201] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2679 [202]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.47
    Notes
    [202] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2321 [203]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6
    Notes
    [203] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7368 [204]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.56
    Notes
    [204] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4606 [205]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Notes
    [205] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3241 [206]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66
    Notes
    [206] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.986 [207]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.57
    Notes
    [207] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.189 [208]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Notes
    [208] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.303 [209]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.67
    Notes
    [209] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.055 [210]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.58
    Notes
    [210] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0415 [211]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.55
    Notes
    [211] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0058 [212]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 -0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.69
    Notes
    [212] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0691 [213]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.62
    Notes
    [213] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0063 [214]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 -0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.58
    Notes
    [214] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0056 [215]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 -0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.71
    Notes
    [215] - Unadjusted p-value

    Secondary: Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

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    End point title
    		 Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
    End point description
    This measure reports results for the 4 items of the Marder hostility/excitement factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. PANSS Marder factor hostility/excitement symptom score for each participant was sum of rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 4, 7, 14, 21, 28, 35 and 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
    least squares mean (standard error)
        Day 4
    -0.4 ( 0.25 )
    -0.3 ( 0.23 )
    -0.7 ( 0.36 )
    -0.5 ( 0.25 )
        Day 7
    -0.5 ( 0.28 )
    -0.5 ( 0.26 )
    -1 ( 0.4 )
    -0.7 ( 0.28 )
        Day 14
    -0.9 ( 0.3 )
    -0.8 ( 0.27 )
    -1.2 ( 0.41 )
    -0.9 ( 0.3 )
        Day 21
    -0.8 ( 0.33 )
    -0.9 ( 0.3 )
    -1.8 ( 0.44 )
    -1 ( 0.32 )
        Day 28
    -0.5 ( 0.41 )
    -0.8 ( 0.36 )
    -1.6 ( 0.53 )
    -1 ( 0.39 )
        Day 35
    -1.4 ( 0.37 )
    -1.5 ( 0.32 )
    -2 ( 0.47 )
    -1.4 ( 0.35 )
        Day 42
    -1.1 ( 0.41 )
    -1.8 ( 0.36 )
    -1.9 ( 0.52 )
    -1.1 ( 0.39 )
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7847 [216]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Notes
    [216] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5859 [217]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.33
    Notes
    [217] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6413 [218]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43
    Notes
    [218] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7307 [219]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.38
    Notes
    [219] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7176 [220]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.37
    Notes
    [220] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.486 [221]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.48
    Notes
    [221] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9321 [222]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [222] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7691 [223]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.39
    Notes
    [223] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5694 [224]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5
    Notes
    [224] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5583 [225]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 1.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45
    Notes
    [225] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7307 [226]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43
    Notes
    [226] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1715 [227]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [227] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4219 [228]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 1.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.55
    Notes
    [228] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7437 [229]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 1.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52
    Notes
    [229] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.311 [230]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.65
    Notes
    [230] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9805 [231]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5
    Notes
    [231] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8741 [232]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.47
    Notes
    [232] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3288 [233]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.7
         upper limit
    		 0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.58
    Notes
    [233] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9336 [234]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.56
    Notes
    [234] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1722 [235]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.7
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52
    Notes
    [235] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1909 [236]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.64
    Notes
    [236] - Unadjusted p-value

    Secondary: Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

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    End point title
    		 Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
    End point description
    This measure reports results for the 4 items of the Marder anxiety/depression factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. PANSS Marder factor anxiety/depression symptom score for each participant was sum of rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 4, 7, 14, 21, 28, 35 and 42
    End point values
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Number of subjects analysed
    96
    111
    45
    99
    Units: score on a scale
    least squares mean (standard error)
        Day 4
    -0.9 ( 0.27 )
    -1.2 ( 0.25 )
    -1 ( 0.38 )
    -0.9 ( 0.27 )
        Day 7
    -1.5 ( 0.3 )
    -2.2 ( 0.28 )
    -1.8 ( 0.43 )
    -1.7 ( 0.3 )
        Day 14
    -1.9 ( 0.31 )
    -2.9 ( 0.28 )
    -2.5 ( 0.42 )
    -2.5 ( 0.3 )
        Day 21
    -2.1 ( 0.32 )
    -3 ( 0.29 )
    -2.7 ( 0.42 )
    -3.1 ( 0.31 )
        Day 28
    -1.9 ( 0.36 )
    -3.2 ( 0.32 )
    -2.8 ( 0.47 )
    -3.4 ( 0.35 )
        Day 35
    -3 ( 0.34 )
    -3.6 ( 0.3 )
    -3.2 ( 0.44 )
    -3.2 ( 0.32 )
        Day 42
    -2.9 ( 0.4 )
    -3.4 ( 0.35 )
    -3.1 ( 0.5 )
    -3 ( 0.38 )
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9851 [237]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.37
    Notes
    [237] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4912 [238]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36
    Notes
    [238] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 4
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8559 [239]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.46
    Notes
    [239] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5635 [240]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [240] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2321 [241]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [241] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 7
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8867 [242]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52
    Notes
    [242] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1499 [243]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Notes
    [243] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.286 [244]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [244] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 14
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8978 [245]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.51
    Notes
    [245] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0283 [246]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1
         upper limit
    		 1.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.44
    Notes
    [246] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8667 [247]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [247] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 21
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5044 [248]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52
    Notes
    [248] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.004 [249]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 2.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Notes
    [249] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.633 [250]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.46
    Notes
    [250] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 28
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2981 [251]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.57
    Notes
    [251] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6556 [252]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45
    Notes
    [252] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2889 [253]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43
    Notes
    [253] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 35
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9399 [254]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Notes
    [254] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 2.5 mg BID v Placebo BID
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8955 [255]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [255] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Asenapine 5 mg BID v Placebo BID
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3681 [256]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.51
    Notes
    [256] - Unadjusted p-value
    Statistical analysis title
    		 Comparison by Treatment Group: Day 42
    Statistical analysis description
    “Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.
    Comparison groups
    Olanzapine 15 mg QD v Placebo BID
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8215 [257]
    Method
    		 MMRM
    Parameter type
    		 LS means difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.62
    Notes
    [257] - Unadjusted p-value

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 30 days after last dose of study drug (Up to approximately 10 weeks)
    Adverse event reporting additional description
    Analysis population is all randomized participants who received ≥1 dose of study drug
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Asenapine 2.5 mg BID
    Reporting group description
    		 Participants were administered one 2.5 mg asenapine tablet BID for 42 days

    Reporting group title
    Asenapine 5 mg BID
    Reporting group description
    		 Participants were administered one 5 mg asenapine tablet BID for 42 days

    Reporting group title
    Olanzapine 15 mg QD
    Reporting group description
    		 Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered

    Reporting group title
    Placebo BID
    Reporting group description
    		 Participants were administered placebo tablets BID for 42 days

    Serious adverse events
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 97 (5.15%)
    5 / 113 (4.42%)
    1 / 46 (2.17%)
    8 / 101 (7.92%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Road traffic accident
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 113 (0.00%)
    0 / 46 (0.00%)
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 113 (0.00%)
    0 / 46 (0.00%)
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 113 (0.00%)
    0 / 46 (0.00%)
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 113 (0.00%)
    0 / 46 (0.00%)
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Small intestinal obstruction
         subjects affected / exposed
    0 / 97 (0.00%)
    1 / 113 (0.88%)
    0 / 46 (0.00%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Psoriasis
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 113 (0.00%)
    0 / 46 (0.00%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 113 (0.00%)
    0 / 46 (0.00%)
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 113 (0.00%)
    0 / 46 (0.00%)
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Homicidal ideation
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 113 (0.00%)
    0 / 46 (0.00%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    2 / 97 (2.06%)
    0 / 113 (0.00%)
    1 / 46 (2.17%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Schizophrenia
         subjects affected / exposed
    0 / 97 (0.00%)
    3 / 113 (2.65%)
    0 / 46 (0.00%)
    2 / 101 (1.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Schizophrenia, paranoid type
         subjects affected / exposed
    0 / 97 (0.00%)
    1 / 113 (0.88%)
    0 / 46 (0.00%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 113 (0.00%)
    0 / 46 (0.00%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Asenapine 2.5 mg BID Asenapine 5 mg BID Olanzapine 15 mg QD Placebo BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 97 (27.84%)
    47 / 113 (41.59%)
    17 / 46 (36.96%)
    29 / 101 (28.71%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 97 (0.00%)
    6 / 113 (5.31%)
    0 / 46 (0.00%)
    0 / 101 (0.00%)
         occurrences all number
    0
    6
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    10 / 97 (10.31%)
    10 / 113 (8.85%)
    4 / 46 (8.70%)
    2 / 101 (1.98%)
         occurrences all number
    12
    10
    6
    2
    Somnolence
         subjects affected / exposed
    3 / 97 (3.09%)
    7 / 113 (6.19%)
    5 / 46 (10.87%)
    0 / 101 (0.00%)
         occurrences all number
    3
    7
    5
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 97 (0.00%)
    2 / 113 (1.77%)
    3 / 46 (6.52%)
    2 / 101 (1.98%)
         occurrences all number
    0
    2
    3
    2
    Dry mouth
         subjects affected / exposed
    0 / 97 (0.00%)
    2 / 113 (1.77%)
    5 / 46 (10.87%)
    1 / 101 (0.99%)
         occurrences all number
    0
    2
    5
    1
    Dyspepsia
         subjects affected / exposed
    1 / 97 (1.03%)
    2 / 113 (1.77%)
    3 / 46 (6.52%)
    2 / 101 (1.98%)
         occurrences all number
    1
    2
    3
    2
    Hypoaesthesia oral
         subjects affected / exposed
    4 / 97 (4.12%)
    7 / 113 (6.19%)
    0 / 46 (0.00%)
    0 / 101 (0.00%)
         occurrences all number
    4
    7
    0
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    3 / 97 (3.09%)
    7 / 113 (6.19%)
    0 / 46 (0.00%)
    3 / 101 (2.97%)
         occurrences all number
    3
    8
    0
    3
    Anxiety
         subjects affected / exposed
    7 / 97 (7.22%)
    8 / 113 (7.08%)
    4 / 46 (8.70%)
    12 / 101 (11.88%)
         occurrences all number
    10
    9
    5
    13
    Insomnia
         subjects affected / exposed
    9 / 97 (9.28%)
    17 / 113 (15.04%)
    4 / 46 (8.70%)
    14 / 101 (13.86%)
         occurrences all number
    9
    21
    4
    20
    Schizophrenia
         subjects affected / exposed
    6 / 97 (6.19%)
    4 / 113 (3.54%)
    0 / 46 (0.00%)
    4 / 101 (3.96%)
         occurrences all number
    6
    4
    0
    4

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Nov 2012
    Amendment 01: Primary reason for amendment was to incorporate revisions to eligibility criteria, drug packaging/labeling and dosing instructions, list of events requiring discontinuation of subject from trial, schedule of assessments and statistical analysis, and to remove text stating that a Data Safety Monitoring Board would participate in study. Original base protocol and Amendments 01 and 02 were submitted together to country authority (Croatia health ministry) that provided approval.
    14 Nov 2012
    Amendment 02: Primary reason for amendment was to incorporate revisions to medications/treatments prohibited prior to and during trial, safety assessments, list of events defined to be serious adverse events, list of closely monitored events and procedures for liver enzyme monitoring. Original base protocol and Amendments 01 and 02 were submitted together to country authority (Croatia health ministry) that provided approval.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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