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Fixed-dose Safety and Efficacy Study of Asenapine for the Treatment of Acute Manic or Mixed Episode in Bipolar 1 Disorder (P05691)

Sponsor
Organon and Co (Industry)
Overall Status
Completed
CT.gov ID
NCT00764478
Collaborator
(none)
367
Enrollment
3
Arms
25.7
Actual Duration (Months)

Study Details

Study Description

Brief Summary

This trial will study the efficacy and safety of a fixed dose of asenapine in participants diagnosed with Bipolar 1 Disorder. Participants who qualify for the study will be randomly assigned to receive a fixed dose of asenapine (either 5 mg or 10 mg twice daily [BID]) or placebo (BID) for 3 weeks. Throughout the trial, observations will be made on each participant at various times to assess the safety and effectiveness of the study treatment. The primary hypothesis is that there is at least one dose of asenapine that is superior to placebo in the change from baseline in manic symptoms (as measured by Young Mania Rating Scale [YMRS]) at Day 21 of the trial.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
367 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3b, Multicenter, Double-Blind, Fixed-Dose, Parallel-Group, Three Week Placebo Controlled Trial Evaluating the Safety and Efficacy of Asenapine in Subjects With Bipolar 1 Disorder Experiencing an Acute Manic or Mixed Episode (Protocol P05691 [Formerly 041044])
Actual Study Start Date :
Apr 6, 2012
Actual Primary Completion Date :
Apr 30, 2014
Actual Study Completion Date :
May 28, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Asenapine 5 mg BID

Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days

Drug: Asenapine
asenapine tablet, 5 mg sublingually BID for 21 days
Other Names:
  • SCH 900274, Saphris®, Sycrest®, Org 5222

    		•
    Experimental: Asenapine 10 mg BID

    Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days

    Drug: Asenapine
    asenapine tablet, 10 mg sublingually BID for 21 days
    Other Names:
  • SCH 900274, Saphris®, Sycrest®, Org 5222

    		•
    Placebo Comparator: Placebo BID

    Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days

    Drug: Placebo
    placebo sublingual tablet, administered BID for 21 days

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score at Day 21 [Baseline and Day 21]

      Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a mixed model repeated measures (MMRM) model. An improvement in symptoms is represented by change from baseline values that are negative.

    Secondary Outcome Measures

    1. Change From Baseline in Clinical Global Impression - Bipolar Mania - Severity of Illness (CGI-BP-S) Overall Score at Day 21 [Baseline and Day 21]

      The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    2. Percentage of Participants Who Are Y-MRS Responders at Day 21 [Day 21]

      Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by Last Observation Carried Forward (LOCF). Y-MRS responders are defined as having a >= 50% decrease from baseline in Y-MRS total score.

    3. Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 [Baseline and Day 2, Day 4, Day 7 and Day 14]

      Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    4. Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 [Day 2, Day 4, Day 7, Day 14]

      Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Y-MRS responders are defined as having a >= 50% decrease from baseline in Y-MRS total score.

    5. Percentage of Participants Who Are Y-MRS Remitters at Day 21 [Day 21]

      Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Y-MRS remitters are defined as having a Y-MRS total score of 12 or lower.

    6. Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 [Day 2, Day 4, Day 7, Day 14, Day 21]

      Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a generalized linear mixed model (GLMM). Y-MRS remitters are defined as having a Y-MRS total score of 12 or lower.

    7. Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score [Baseline and Day 7 and Day 21]

      The MADRS measures depression and consists of 10 items, each rated on a scale from 0 to 6. The MADRS total score sums the scores from the 10 items, ranging from 0 to 60, with a higher numeric rating implying a greater degree of symptom severity. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.

    8. Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 [Baseline and Day 2, Day 4, Day 7, Day 14]

      The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    9. Change From Baseline in CGI-BP-S Mania Score [Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21]

      The CGI-BP-S mania is a score that assesses the severity of the mania component of bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.

    10. Change From Baseline in CGI-BP-S Depression Score [Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21]

      The CGI-BP-S depression is a score that assesses the severity of the depression component of bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.

    11. Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score [Day 2, Day 4, Day 7, Day 14, and Day 21]

      The CGI-BP-I overall is a score on a 7-point scale for assessing the change from preceding phase of overall symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I overall score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.

    12. Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score [Day 2, Day 4, Day 7, Day 14, and Day 21]

      The CGI-BP-I mania is a score on a 7-point scale for assessing the change from preceding phase of mania symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I mania score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.

    13. Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score [Day 2, Day 4, Day 7, Day 14, and Day 21]

      The CGI-BP-I depression is a score on a 7-point scale for assessing the change from preceding phase of depression symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I depression score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.

    14. Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score [Baseline and Day 7, Day 14, Day 21]

      PANSS total score measures symptoms of schizophrenia and consists of responses to 30 items: 7 items from the positive subscale (P1-P7), 7 items from the negative subscale (N1-N7) and 16 items from the general psychopathology subscale (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS total score sums the scores from all 30 items, and ranges from 30 to 210, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    15. Change From Baseline in PANSS Negative Subscale Score [Baseline and Day 7, Day 14, Day 21]

      PANSS Negative subscale measures symptoms of schizophrenia and consists of responses to 7 items (N1-N7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Negative subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    16. Change From Baseline in PANSS Positive Subscale Score [Baseline and Day 7, Day 14, Day 21]

      PANSS Positive subscale measures symptoms of schizophrenia and consists of responses to 7 items (P1-P7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Positive subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    17. Change From Baseline in PANSS General Psychopathology Subscale Score [Baseline and Day 7, Day 14, Day 21]

      PANSS General Psychopathology subscale measures symptoms of schizophrenia and consists of responses to 16 items (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS General Psychopathology subscale sums the scores from all 16 items and ranges from 16 to 112, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    18. Change From Baseline in PANSS Marder Factor Positive Symptom Score [Baseline and Day 7, Day 14, Day 21]

      PANSS Marder Factor Positive symptom score measures symptoms of schizophrenia and consists of responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Positive symptom score sums the scores from all 8 items and ranges from 8 to 56, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    19. Change From Baseline in PANSS Marder Factor Negative Symptom Score [Baseline and Day 7, Day 14, Day 21]

      PANSS Marder Factor Negative symptom score measures symptoms of schizophrenia and consists of responses to 7 items (N1,N2,N3,N4,N6,G7,G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Negative symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    20. Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score [Baseline and Day 7, Day 14, Day 21]

      PANSS Marder Factor Disorganized Thought symptom score measures symptoms of schizophrenia and consists of responses to 7 items (P2,N5,G5,G10,G11,G13,G15). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Disorganized Thought symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    21. Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score [Baseline and Day 7, Day 14, Day 21]

      PANSS Marder Factor Hostility/Excitement symptom score measures symptoms of schizophrenia and consists of responses to 4 items (P4,P7,G8,G14). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Hostility/Excitement symptom score sums the score from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    22. Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score [Baseline and Day 7, Day14, Day 21]

      PANSS Marder Factor Anxiety/Depression symptom score measures symptoms of schizophrenia and consists of responses to 4 items (G2,G3,G4,G6). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Anxiety/Depression symptom score sums the scores from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Each participant must be at least 18 years of age

    • Male, or a female who is not of child-bearing potential or who is non-pregnant, non-lactating, and is using a medically accepted method of contraception

    • Each participant must have a current diagnosis of Bipolar I Disorder, current episode manic or mixed

    • Each participant must be confirmed to be experiencing an acute manic or mixed bipolar 1 episode

    • Each participant must have discontinued the use of all prohibited psychotropic medications

    Exclusion Criteria:

    • A participant must not have a primary Axis I disorder other than Bipolar 1 Disorder (i.e., an Axis 1 disorder other than Bipolar 1 Disorder that is primarily responsible for current symptoms and functional impairment)

    • A participant must not currently (within the past 6 months) meet the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR™) criteria for substance abuse or dependence (excluding nicotine)

    • A participant must not be at imminent risk of self-harm or harm to others, in the investigator's opinion based on clinical interview and responses provided on the Columbia Suicide Severity Rating Scale (CSSRS).

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Organon and Co

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Organon and Co
    ClinicalTrials.gov Identifier:
    NCT00764478
    Other Study ID Numbers:
    • P05691
    • 2010-018409-13
    • MK-8274-003
    First Posted:
    Oct 2, 2008
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Disease
    Asenapine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually twice daily (BID) for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Period Title: Overall Study
    STARTED 122 119 126
    COMPLETED 107 97 118
    NOT COMPLETED 15 22 8

    Baseline Characteristics

    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID Total
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days Total of all reporting groups
    Overall Participants 122 119 126 367
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    44.3
    (10.82)
    42.5
    (11.06)
    44.6
    (11.54)
    43.8
    (11.16)
    Sex: Female, Male (Count of Participants)
    Female
    65
    53.3%
    64
    53.8%
    72
    57.1%
    201
    54.8%
    Male
    57
    46.7%
    55
    46.2%
    54
    42.9%
    166
    45.2%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score at Day 21
    Description Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a mixed model repeated measures (MMRM) model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 126
    Least Squares Mean (Standard Error) [Score on a scale]
    -14.4
    (1.02)
    -14.9
    (1.04)
    -10.9
    (0.99)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0136
    Comments Adjusted p-value from graphical approach to control Type 1 error rate among primary and secondary hypotheses
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -3.5
    Confidence Interval (2-Sided) 95%
    -6.3 to -0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.41
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0100
    Comments Adjusted p-value from graphical approach to control Type 1 error rate among primary and secondary hypotheses
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -4.0
    Confidence Interval (2-Sided) 95%
    -6.9 to -1.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.43
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    2. Secondary Outcome
    Title Change From Baseline in Clinical Global Impression - Bipolar Mania - Severity of Illness (CGI-BP-S) Overall Score at Day 21
    Description The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. One participant from the Placebo BID arm missed a baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 125
    Least Squares Mean (Standard Error) [Score on a scale]
    -1.6
    (0.12)
    -1.7
    (0.12)
    -1.1
    (0.11)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0100
    Comments Adjusted p-value from Hochberg's method for testing two secondary efficacy hypotheses
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -0.8 to -0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0052
    Comments Adjusted p-value from Hochberg's method for testing two secondary efficacy hypotheses
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -0.9 to -0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    3. Secondary Outcome
    Title Percentage of Participants Who Are Y-MRS Responders at Day 21
    Description Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by Last Observation Carried Forward (LOCF). Y-MRS responders are defined as having a >= 50% decrease from baseline in Y-MRS total score.
    Time Frame Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 126
    Number [Percentage of participants]
    45.0
    36.9%
    46.9
    39.4%
    39.7
    31.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5352
    Comments Overall adjusted p-value from Hochberg's method for testing two secondary efficacy hypotheses
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.4274
    Comments Overall adjusted p-value from Hochberg's method for testing two secondary efficacy hypotheses
    Method Cochran-Mantel-Haenszel
    Comments
    4. Secondary Outcome
    Title Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14
    Description Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 2, Day 4, Day 7 and Day 14

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 126
    Day 2
    -5.6
    (0.57)
    -5.8
    (0.59)
    -2.9
    (0.56)
    Day 4
    -8.6
    (0.67)
    -8.6
    (0.68)
    -4.9
    (0.64)
    Day 7
    -10.0
    (0.81)
    -10.7
    (0.83)
    -6.6
    (0.79)
    Day 14
    -11.1
    (0.98)
    -12.5
    (1.00)
    -9.4
    (0.95)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0007
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -2.7
    Confidence Interval (2-Sided) 95%
    -4.2 to -1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.78
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -2.9
    Confidence Interval (2-Sided) 95%
    -4.4 to -1.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.79
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -3.6
    Confidence Interval (2-Sided) 95%
    -5.4 to -1.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.91
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -3.7
    Confidence Interval (2-Sided) 95%
    -5.5 to -1.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.92
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0021
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -3.5
    Confidence Interval (2-Sided) 95%
    -5.7 to -1.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.12
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -4.2
    Confidence Interval (2-Sided) 95%
    -6.4 to -2.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.13
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1907
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -4.4 to 0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.35
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0238
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -5.8 to -0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.37
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    5. Secondary Outcome
    Title Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14
    Description Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Y-MRS responders are defined as having a >= 50% decrease from baseline in Y-MRS total score.
    Time Frame Day 2, Day 4, Day 7, Day 14

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 126
    Day 2 (n = 117,111,123)
    12.0
    9.8%
    14.4
    12.1%
    8.9
    7.1%
    Day 4 (n = 120,113,126)
    21.7
    17.8%
    23.0
    19.3%
    8.7
    6.9%
    Day 7 (n = 120,113,126)
    31.7
    26%
    28.3
    23.8%
    19.8
    15.7%
    Day 14 (n = 120,113,126)
    36.7
    30.1%
    40.7
    34.2%
    33.3
    26.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2922
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0011
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0011
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0194
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0841
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.4858
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2496
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    6. Secondary Outcome
    Title Percentage of Participants Who Are Y-MRS Remitters at Day 21
    Description Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Y-MRS remitters are defined as having a Y-MRS total score of 12 or lower.
    Time Frame Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 126
    Number [Percentage of participants]
    34.2
    28%
    38.1
    32%
    30.2
    24%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2912
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1151
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    7. Secondary Outcome
    Title Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21
    Description Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a generalized linear mixed model (GLMM). Y-MRS remitters are defined as having a Y-MRS total score of 12 or lower.
    Time Frame Day 2, Day 4, Day 7, Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 126
    Day 2 (n= 117,111, 123)
    8.5
    7%
    11.7
    9.8%
    5.7
    4.5%
    Day 4 (n= 104, 106,118)
    17.3
    14.2%
    15.1
    12.7%
    10.2
    8.1%
    Day 7 (n= 104, 101,110)
    26.9
    22%
    24.8
    20.8%
    17.3
    13.7%
    Day 14 (n= 96, 91,102)
    28.1
    23%
    27.5
    23.1%
    24.5
    19.4%
    Day 21 (n= 86, 83,93)
    40.7
    33.4%
    43.4
    36.5%
    34.4
    27.3%
    8. Secondary Outcome
    Title Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score
    Description The MADRS measures depression and consists of 10 items, each rated on a scale from 0 to 6. The MADRS total score sums the scores from the 10 items, ranging from 0 to 60, with a higher numeric rating implying a greater degree of symptom severity. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 7 and Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 115 110 123
    Day 7 (n=112,106, 117)
    -4.3
    (0.47)
    -4.2
    (0.48)
    -2.3
    (0.46)
    Day 21 (n =115, 110,123)
    -4.6
    (0.61)
    -5.1
    (0.63)
    -2.5
    (0.60)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0019
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0045
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0112
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0021
    Comments
    Method ANCOVA
    Comments
    9. Secondary Outcome
    Title Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14
    Description The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 2, Day 4, Day 7, Day 14

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. One participant from the Placebo BID arm missed a baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 125
    Day 2
    -0.5
    (0.05)
    -0.4
    (0.06)
    -0.2
    (0.05)
    Day 4
    -0.8
    (0.07)
    -0.7
    (0.07)
    -0.4
    (0.07)
    Day 7
    -1.0
    (0.09)
    -1.1
    (0.09)
    -0.7
    (0.09)
    Day 14
    -1.3
    (0.10)
    -1.3
    (0.11)
    -1.0
    (0.10)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.4 to -0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.07
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0076
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -0.3 to -0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.07
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -0.6 to -0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.10
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0040
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.5 to -0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.10
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0061
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.6 to -0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.12
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0031
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -0.6 to -0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1086
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.14
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0376
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.6 to -0.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.15
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    10. Secondary Outcome
    Title Change From Baseline in CGI-BP-S Mania Score
    Description The CGI-BP-S mania is a score that assesses the severity of the mania component of bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement, and had evaluable post-baseline measurement at timepoint. One participant from the Placebo BID arm missed a baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 125
    Day 2 (n=118,111,122)
    -0.4
    (0.06)
    -0.4
    (0.06)
    -0.1
    (0.06)
    Day 4 (n=120,113,125)
    -0.7
    (0.07)
    -0.7
    (0.08)
    -0.3
    (0.07)
    Day 7 (n=120,113,125)
    -0.9
    (0.09)
    -1.0
    (0.09)
    -0.7
    (0.09)
    Day 14 (n=120,113,125)
    -1.2
    (0.10)
    -1.3
    (0.11)
    -1.0
    (0.10)
    Day 21 (n=120,113,125)
    -1.4
    (0.11)
    -1.5
    (0.12)
    -1.1
    (0.11)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0005
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0026
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0007
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0387
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0059
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3110
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0613
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0640
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0139
    Comments
    Method ANCOVA
    Comments
    11. Secondary Outcome
    Title Change From Baseline in CGI-BP-S Depression Score
    Description The CGI-BP-S depression is a score that assesses the severity of the depression component of bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 125
    Day 2 (n=118,111,122)
    -0.2
    (0.06)
    -0.2
    (0.06)
    -0.2
    (0.06)
    Day 4 (n=120,113,125)
    -0.3
    (0.06)
    -0.3
    (0.06)
    -0.3
    (0.06)
    Day 7 (n=120,113,125)
    -0.3
    (0.07)
    -0.4
    (0.07)
    -0.1
    (0.07)
    Day 14 (n=120,113,125)
    -0.4
    (0.07)
    -0.5
    (0.07)
    -0.2
    (0.07)
    Day 21 (n=120,113,125)
    -0.4
    (0.08)
    -0.5
    (0.08)
    -0.1
    (0.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9708
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7891
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5222
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8686
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0696
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0049
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0196
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0032
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0061
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0012
    Comments
    Method ANCOVA
    Comments
    12. Secondary Outcome
    Title Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score
    Description The CGI-BP-I overall is a score on a 7-point scale for assessing the change from preceding phase of overall symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I overall score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.
    Time Frame Day 2, Day 4, Day 7, Day 14, and Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 126
    Day 2 (n=118,111,123)
    50.8
    41.6%
    45.9
    38.6%
    37.4
    29.7%
    Day 4 (n=120,113,126)
    64.2
    52.6%
    64.6
    54.3%
    55.6
    44.1%
    Day 7 (n=120,113,126)
    73.3
    60.1%
    78.8
    66.2%
    61.1
    48.5%
    Day 14 (n=120,113,126)
    70.8
    58%
    83.2
    69.9%
    65.1
    51.7%
    Day 21 (n=120,113,126)
    74.2
    60.8%
    82.3
    69.2%
    64.3
    51%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0147
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0720
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1213
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0588
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0200
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0017
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2401
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0009
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0525
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0025
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    13. Secondary Outcome
    Title Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score
    Description The CGI-BP-I mania is a score on a 7-point scale for assessing the change from preceding phase of mania symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I mania score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.
    Time Frame Day 2, Day 4, Day 7, Day 14, and Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 120 113 126
    Day 2 (n=118,111,123)
    49.2
    40.3%
    45.9
    38.6%
    37.4
    29.7%
    Day 4 (n=120,113,126)
    64.2
    52.6%
    66.4
    55.8%
    55.6
    44.1%
    Day 7 (n=120,113,126)
    74.2
    60.8%
    80.5
    67.6%
    63.5
    50.4%
    Day 14 (n=120,113,126)
    75.8
    62.1%
    82.3
    69.2%
    66.7
    52.9%
    Day 21 (n=120,113,126)
    79.2
    64.9%
    84.1
    70.7%
    66.7
    52.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0377
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0771
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1264
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0280
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0583
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0021
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0866
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0048
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0147
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0030
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    14. Secondary Outcome
    Title Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score
    Description The CGI-BP-I depression is a score on a 7-point scale for assessing the change from preceding phase of depression symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I depression score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.
    Time Frame Day 2, Day 4, Day 7, Day 14, and Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 117 106 121
    Day 2 (n=113, 103, 116)
    21.2
    17.4%
    28.2
    23.7%
    11.2
    8.9%
    Day 4 (n=116, 106, 119)
    26.7
    21.9%
    32.1
    27%
    19.3
    15.3%
    Day 7 (n=117, 106, 119)
    31.6
    25.9%
    35.8
    30.1%
    23.5
    18.7%
    Day 14 (n=117, 106, 120)
    31.6
    25.9%
    42.5
    35.7%
    26.7
    21.2%
    Day 21 (n=117, 106, 121)
    32.5
    26.6%
    44.3
    37.2%
    28.9
    22.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0104
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 2
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0005
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0692
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 4
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0128
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0809
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0260
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2576
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0077
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3960
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0141
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    15. Secondary Outcome
    Title Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score
    Description PANSS total score measures symptoms of schizophrenia and consists of responses to 30 items: 7 items from the positive subscale (P1-P7), 7 items from the negative subscale (N1-N7) and 16 items from the general psychopathology subscale (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS total score sums the scores from all 30 items, and ranges from 30 to 210, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 7, Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 115 110 123
    Day 7
    -6.9
    (0.77)
    -6.9
    (0.79)
    -3.9
    (0.76)
    Day 14
    -7.5
    (0.96)
    -8.4
    (0.99)
    -5.2
    (0.94)
    Day 21
    -9.3
    (1.02)
    -8.8
    (1.05)
    -5.5
    (1.00)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0056
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -3.0
    Confidence Interval (2-Sided) 95%
    -5.1 to -0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.06
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0068
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -2.9
    Confidence Interval (2-Sided) 95%
    -5.0 to -0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.08
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0743
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -5.0 to 0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.33
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0177
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -3.2
    Confidence Interval (2-Sided) 95%
    -5.9 to -0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.35
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0081
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -3.8
    Confidence Interval (2-Sided) 95%
    -6.6 to -1.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.41
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0247
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -3.2
    Confidence Interval (2-Sided) 95%
    -6.1 to -0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.43
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    16. Secondary Outcome
    Title Change From Baseline in PANSS Negative Subscale Score
    Description PANSS Negative subscale measures symptoms of schizophrenia and consists of responses to 7 items (N1-N7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Negative subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 7, Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 115 110 123
    Day 7
    -0.5
    (0.22)
    -0.8
    (0.22)
    -0.5
    (0.21)
    Day 14
    -0.8
    (0.23)
    -0.7
    (0.24)
    -0.8
    (0.23)
    Day 21
    -0.4
    (0.28)
    -0.0
    (0.29)
    -0.4
    (0.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9808
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.30
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2830
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.9 to 0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.31
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9751
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7879
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9654
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.38
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3917
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -0.4 to 1.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.39
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    17. Secondary Outcome
    Title Change From Baseline in PANSS Positive Subscale Score
    Description PANSS Positive subscale measures symptoms of schizophrenia and consists of responses to 7 items (P1-P7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Positive subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 7, Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 115 110 123
    Day 7
    -2.4
    (0.30)
    -2.8
    (0.31)
    -1.4
    (0.29)
    Day 14
    -2.3
    (0.37)
    -3.2
    (0.38)
    -2.1
    (0.36)
    Day 21
    -3.5
    (0.37)
    -3.9
    (0.38)
    -2.4
    (0.36)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0120
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -1.8 to -0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0011
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -2.2 to -0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.42
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.6885
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -1.2 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.51
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0398
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -2.1 to -0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.52
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0258
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -2.1 to -0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.51
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0031
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -2.5 to -0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.51
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    18. Secondary Outcome
    Title Change From Baseline in PANSS General Psychopathology Subscale Score
    Description PANSS General Psychopathology subscale measures symptoms of schizophrenia and consists of responses to 16 items (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS General Psychopathology subscale sums the scores from all 16 items and ranges from 16 to 112, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 7, Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 115 110 123
    Day 7
    -4.0
    (0.46)
    -3.3
    (0.48)
    -2.1
    (0.46)
    Day 14
    -4.5
    (0.57)
    -4.6
    (0.59)
    -2.4
    (0.56)
    Day 21
    -5.5
    (0.61)
    -4.9
    (0.62)
    -2.9
    (0.59)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0033
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -3.2 to -0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.64
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0622
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.5 to 0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.65
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0083
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -3.6 to -0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.79
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0064
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -3.8 to -0.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.80
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0022
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -2.6
    Confidence Interval (2-Sided) 95%
    -4.3 to -0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.84
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0196
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -3.7 to -0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.85
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    19. Secondary Outcome
    Title Change From Baseline in PANSS Marder Factor Positive Symptom Score
    Description PANSS Marder Factor Positive symptom score measures symptoms of schizophrenia and consists of responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Positive symptom score sums the scores from all 8 items and ranges from 8 to 56, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 7, Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 115 110 123
    Day 7
    -1.9
    (0.29)
    -1.9
    (0.29)
    -1.3
    (0.28)
    Day 14
    -1.6
    (0.33)
    -2.5
    (0.34)
    -1.6
    (0.33)
    Day 21
    -2.6
    (0.34)
    -2.9
    (0.35)
    -1.7
    (0.33)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1883
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -1.3 to 0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.40
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1684
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -1.3 to 0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.40
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9522
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.0
    Confidence Interval (2-Sided) 95%
    -0.9 to 0.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.46
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0514
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -1.8 to 0.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.47
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0531
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -1.8 to 0.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.47
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0078
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -2.2 to -0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.48
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    20. Secondary Outcome
    Title Change From Baseline in PANSS Marder Factor Negative Symptom Score
    Description PANSS Marder Factor Negative symptom score measures symptoms of schizophrenia and consists of responses to 7 items (N1,N2,N3,N4,N6,G7,G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Negative symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 7, Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 115 110 123
    Day 7
    -0.5
    (0.23)
    -0.8
    (0.24)
    -0.5
    (0.23)
    Day 14
    -0.6
    (0.24)
    -0.5
    (0.25)
    -0.7
    (0.24)
    Day 21
    -0.1
    (0.27)
    0.1
    (0.28)
    -0.1
    (0.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7746
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2754
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -1.0 to 0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9109
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7295
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9800
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.38
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5122
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -0.5 to 1.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.38
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    21. Secondary Outcome
    Title Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score
    Description PANSS Marder Factor Disorganized Thought symptom score measures symptoms of schizophrenia and consists of responses to 7 items (P2,N5,G5,G10,G11,G13,G15). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Disorganized Thought symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 7, Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 115 110 123
    Day 7
    -1.1
    (0.21)
    -1.3
    (0.22)
    -0.7
    (0.21)
    Day 14
    -1.5
    (0.26)
    -1.8
    (0.27)
    -1.2
    (0.26)
    Day 21
    -2.0
    (0.28)
    -1.7
    (0.29)
    -1.5
    (0.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2191
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -0.9 to 0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0589
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -1.1 to 0.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3683
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -1.0 to 0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.36
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0982
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -1.3 to 0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.37
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1969
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -1.3 to 0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.38
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5615
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -1.0 to 0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.39
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    22. Secondary Outcome
    Title Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score
    Description PANSS Marder Factor Hostility/Excitement symptom score measures symptoms of schizophrenia and consists of responses to 4 items (P4,P7,G8,G14). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Hostility/Excitement symptom score sums the score from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 7, Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 115 110 123
    Day 7
    -1.7
    (0.24)
    -1.7
    (0.25)
    -0.9
    (0.24)
    Day 14
    -1.8
    (0.28)
    -2.0
    (0.29)
    -1.2
    (0.27)
    Day 21
    -2.6
    (0.29)
    -2.5
    (0.30)
    -1.5
    (0.28)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0101
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -1.5 to -0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0146
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -1.5 to -0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0861
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -1.4 to 0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.39
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0342
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.39
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0037
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.0 to -0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.40
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0096
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -1.9 to -0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    23. Secondary Outcome
    Title Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score
    Description PANSS Marder Factor Anxiety/Depression symptom score measures symptoms of schizophrenia and consists of responses to 4 items (G2,G3,G4,G6). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Anxiety/Depression symptom score sums the scores from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame Baseline and Day 7, Day14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    Measure Participants 115 110 123
    Day 7
    -1.7
    (0.24)
    -1.3
    (0.24)
    -0.7
    (0.23)
    Day 14
    -2.0
    (0.26)
    -1.7
    (0.27)
    -0.7
    (0.26)
    Day 21
    -2.1
    (0.30)
    -1.9
    (0.30)
    -1.0
    (0.29)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0019
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter Least Square (LS) means difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -1.7 to -0.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 7
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0791
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -1.2 to 0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0006
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.0 to -0.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.36
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 14
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0123
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.37
    Estimation Comments Asenapine 10 mg BID minus Placebo BID
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Asenapine 5 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0054
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -2.0 to -0.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments Asenapine 5 mg BID minus Placebo BID
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Asenapine 10 mg BID, Placebo BID
    Comments Day 21
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0350
    Comments
    Method MMRM
    Comments
    Method of Estimation Estimation Parameter LS means difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -1.7 to -0.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments Asenapine 10 mg BID minus Placebo BID

    Adverse Events

    Time Frame Up to 33 days after end of treatment (up to 54 days)
    Adverse Event Reporting Description Randomized participants who received at least one dose of trial medication
    Arm/Group Title Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Arm/Group Description Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days
    All Cause Mortality
    Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/122 (2.5%) 1/119 (0.8%) 2/126 (1.6%)
    Infections and infestations
    Pneumonia 1/122 (0.8%) 1 0/119 (0%) 0 0/126 (0%) 0
    Injury, poisoning and procedural complications
    Facial bones fracture 0/122 (0%) 0 0/119 (0%) 0 1/126 (0.8%) 1
    Foot fracture 0/122 (0%) 0 0/119 (0%) 0 1/126 (0.8%) 1
    Road traffic accident 0/122 (0%) 0 0/119 (0%) 0 1/126 (0.8%) 1
    Psychiatric disorders
    Bipolar I disorder 2/122 (1.6%) 2 0/119 (0%) 0 1/126 (0.8%) 1
    Mania 1/122 (0.8%) 1 0/119 (0%) 0 0/126 (0%) 0
    Suicidal ideation 0/122 (0%) 0 1/119 (0.8%) 1 0/126 (0%) 0
    Suicide attempt 0/122 (0%) 0 1/119 (0.8%) 1 0/126 (0%) 0
    Other (Not Including Serious) Adverse Events
    Asenapine 5 mg BID Asenapine 10 mg BID Placebo BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 43/122 (35.2%) 67/119 (56.3%) 24/126 (19%)
    Gastrointestinal disorders
    Hypoaesthesia oral 15/122 (12.3%) 15 27/119 (22.7%) 28 2/126 (1.6%) 2
    Nausea 4/122 (3.3%) 4 6/119 (5%) 6 4/126 (3.2%) 6
    Metabolism and nutrition disorders
    Increased appetite 1/122 (0.8%) 1 7/119 (5.9%) 7 3/126 (2.4%) 3
    Nervous system disorders
    Akathisia 5/122 (4.1%) 5 18/119 (15.1%) 25 1/126 (0.8%) 1
    Dizziness 4/122 (3.3%) 5 6/119 (5%) 6 6/126 (4.8%) 6
    Dysgeusia 4/122 (3.3%) 4 11/119 (9.2%) 11 0/126 (0%) 0
    Headache 9/122 (7.4%) 10 6/119 (5%) 7 9/126 (7.1%) 11
    Sedation 12/122 (9.8%) 12 18/119 (15.1%) 19 2/126 (1.6%) 2
    Somnolence 12/122 (9.8%) 12 14/119 (11.8%) 15 3/126 (2.4%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The investigator agrees to provide to the sponsor 45 days to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including without limitation, slides and texts of oral or other public presentations and texts of any transmission through any electronic media, eg, any computer access system such as the Internet, World Wide Web, etc) that report any results of the trial.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Organon and Co
    ClinicalTrials.gov Identifier:
    NCT00764478
    Other Study ID Numbers:
    • P05691
    • 2010-018409-13
    • MK-8274-003
    First Posted:
    Oct 2, 2008
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022