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Fixed Dose Efficacy and Safety Study of Asenapine for the Treatment of Schizophrenia in Adolescents (P05896)

Sponsor
Organon and Co (Industry)
Overall Status
Completed
CT.gov ID
NCT01190254
Collaborator
(none)
306
Enrollment
3
Arms
30.1
Actual Duration (Months)

Study Details

Study Description

Brief Summary

This study is designed to evaluate whether asenapine, which is approved by the United States Food and Drug Administration (US FDA) for acute treatment of schizophrenia in adults, is also effective in adolescents with schizophrenia. Participants who qualify for the study will be randomly assigned to receive a fixed dose of asenapine (either 2.5 mg or 5 mg twice daily [BID]) or placebo for 8 weeks. Throughout the study, observations will be made on each participant at various times to assess the efficacy and safety of the study treatment. The primary objective of the trial is to demonstrate significant superiority of at least one asenapine dose to placebo, as measured by the change from baseline of the Positive and Negative Syndrome Scale (PANSS) total score at Day 56.

Condition or Disease Intervention/Treatment Phase
  • Drug: asenapine 2.5 mg
  • Drug: asenapine 5.0 mg
  • Drug: placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
306 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
An 8-week, Placebo-controlled, Double-blind, Randomized, Fixed-dose Efficacy and Safety Trial of Asenapine in Adolescent Subjects With Schizophrenia
Actual Study Start Date :
Sep 28, 2010
Actual Primary Completion Date :
Mar 10, 2013
Actual Study Completion Date :
Apr 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Asenapine 2.5 mg BID

Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks.

Drug: asenapine 2.5 mg
asenapine 2.5 mg tablets for sublingual administration
Other Names:
  • Saphris®, SCH 900274, Org 5222

    		•
    Experimental: Asenapine 5.0 mg BID

    Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period.

    Drug: asenapine 2.5 mg
    asenapine 2.5 mg tablets for sublingual administration
    Other Names:
  • Saphris®, SCH 900274, Org 5222

    • Drug: asenapine 5.0 mg
    asenapine 5.0 mg tablets for sublingual administration
    Other Names:
  • Saphris®, SCH 900274, Org 5222

    		•
    Placebo Comparator: Placebo

    Participants receive placebo asenapine tablets sublingually BID for 8 weeks.

    Drug: placebo
    asenapine-matched placebo tablets for sublingual administration

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 56 [Baseline and Day 56]

      The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    Secondary Outcome Measures

    1. Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Day 56 [Baseline and Day 56]

      Change from baseline in CGI-S score at Day 56 is the Key Secondary Outcome Measure. CGI-S is a 7-point scale for assessing the global severity of the participant's illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    2. Change From Baseline in PANSS Positive Subscale Score at Day 56 [Baseline and Day 56]

      This measure reports results for the 7 items of the positive subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive subscale score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    3. Change From Baseline in PANSS Negative Subscale Score at Day 56 [Baseline and Day 56]

      This measure reports results for the 7 items of the negative subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS negative subscale score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    4. Change From Baseline in PANSS Positive and Negative Subscale Scores Combined at Day 56 [Baseline and Day 56]

      This measure reports results for the combined positive subscale (7 items) and negative subscale (7 items) of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each of the total 14 items in the combined positive and negative subscales, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive and negative subscale scores combined for each participant was calculated as the sum of the rating assigned to each of the 14 combined subscale items, and ranged from 14 to 98 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    5. Change From Baseline in PANSS General Psychopathology Subscale Score at Day 56 [Baseline and Day 56]

      This measure reports results for the 16 items of the general psychopathology subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS general psychopathology subscale score for each participant was calculated as the sum of the rating assigned to each of the 16 subscale items, and ranged from 16 to 112 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    6. Change From Baseline in PANSS Marder Positive Symptoms Factor Score at Day 56 [Baseline and Day 56]

      This measure reports results for the 8 items of the Marder positive symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items (Marder et al. J Clin Psychiatry 1997;58(12):538-46). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder positive symptoms factor score for each participant was calculated as the sum of the rating assigned to each of the 8 applicable Marder factor items, and ranged from 8 to 56 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    7. Change From Baseline in PANSS Marder Negative Symptoms Factor Score at Day 56 [Baseline and Day 56]

      This measure reports results for the 7 items of the Marder negative symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder negative symptoms factor score for each participant was calculated as the sum of the rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    8. Change From Baseline in PANSS Marder Disorganized Thoughts Factor Score at Day 56 [Baseline and Day 56]

      This measure reports results for the 7 items of the Marder disorganized thoughts factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder disorganized thoughts factor score for each participant was calculated as the sum of the rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    9. Change From Baseline in PANSS Marder Hostility/Excitement Factor Score at Day 56 [Baseline and Day 56]

      This measure reports results for the 4 items of the Marder hostility/excitement factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder hostility/excitement factor score for each participant was calculated as the sum of the rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    10. Change From Baseline in PANSS Marder Anxiety/Depression Factor Score at Day 56 [Baseline and Day 56]

      This measure reports results for the 4 items of the Marder anxiety/depression factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder anxiety/depression factor score for each participant was calculated as the sum of the rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

    11. Total PANSS 30% Responders [Baseline up to Day 56]

      A Total PANSS 30% responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS Total score at the last available assessment of the study for that participant (i.e., endpoint). The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms.

    12. Kaplan-Meier Estimate of Cumulative Percentage of Participants With Total PANSS 30% Response at End of Study [Baseline up to approximately Day 59]

      A total PANSS 30% response was defined as a reduction from baseline of at least 30% in the PANSS Total score. The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The Kaplan-Meier estimate reports the cumulative percentage of participants with total PANSS 30% response from first drug intake up to approximately Day 59.

    13. Clinical Global Impression of Improvement (CGI-I) Score at Day 56 [Baseline and Day 56]

      CGI-I is a 7-point scale for assessing the global improvement of the participant's illness relative to baseline, with ratings from 1=very much improved to 7=very much worse.

    14. CGI-I Responders [Baseline up to Day 56]

      A CGI-I responder was defined as a participant who had a CGI-I score of 1 (very much improved) or 2 (much improved) at the last available assessment of the study for that participant (i.e., endpoint). CGI-I is a 7-point scale for assessing the global improvement of the participant's illness relative to baseline, with ratings from 1=very much improved to 7=very much worse.

    15. Kaplan-Meier Estimate of Cumulative Percentage of Participants With CGI-I Response at End of Study [Baseline up to approximately Day 58]

      CGI-I response was defined as the occurrence of a CGI-I score of 1 (very much improved) or 2 (much improved). CGI-I is a 7-point scale for assessing the global improvement of the participant's illness relative to baseline, with ratings from 1=very much improved to 7=very much worse. The Kaplan-Meier estimate reports the cumulative percentage of participants with CGI-I response from first drug intake up to approximately Day 58.

    16. Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Day 56 [Baseline and Day 56]

      CGAS is a 100-point scale measuring psychological, social, and school functioning in children aged 6-17. Minimum scores ranged from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The reported measure is the change from baseline at Day 56; improvement in functioning is represented by positive values.

    17. Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 56 [Baseline and Day 56]

      PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant was calculated as the sum of the rating assigned to each of the first 14 items, and ranged from 14 to 70 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 56; improvement in quality of life is represented by positive values. This analysis used a last-observation-carried-forward (LOCF) approach; if no Day 56 value was available for a participant, the last available assessment prior to the Day 56 assessment was used.

    18. Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 56 [Baseline and Day 56]

      PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The Item 15 result is defined to be the PQ-LES-Q overall score, and ranged from 1 to 5 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 56; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 56 value was available for a participant, the last available assessment prior to the Day 56 assessment was used.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Each participant must have schizophrenia, diagnosed and confirmed by board-eligible or board certified psychiatrists with at least two years of specialization in pediatric/adolescent psychiatric medicine.

    • Each participant must be ≥12 years of age and <18 years of age.

    • Each participant must have a minimum PANSS total score of 80 at Screening and Baseline.

    • Each participant must have a score of at least 4 (moderate) on two or more of the five items in the positive subscale of the PANSS (delusions, conceptual disorganization, hallucinatory behavior, grandiosity, suspiciousness/ persecution) at Screening and Baseline.

    • Each participant must have a CGI-S scale score of ≥4 at Screening and Baseline.

    • Each participant must taper off all prohibited psychotropic medications (including antipsychotics, antidepressants, and mood stabilizers) prior to Baseline.

    • Each participant must agree not to begin formal, structured psychotherapy during the trial.

    Exclusion Criteria:

    • A participant must not have a diagnosis of schizoaffective disorder; schizophrenia of residual subtype; schizophrenia of catatonic subtype, or schizophrenia with "continuous," "single episode in partial remission," or "single episode in full remission" course specifiers.

    • A participant must not have a primary Axis I diagnosis other than schizophrenia and must not have a comorbid Axis I diagnosis that is primarily responsible for current symptoms and functional impairment.

    • A participant must not have a known or suspected diagnosis of mental retardation or organic brain disorder.

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

    • A participant must not have a diagnosis of psychotic disorder or a behavioral disturbance thought to be substance induced or due to substance abuse.

    • 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 (C-SSRS).

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Organon and Co

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Organon and Co
    ClinicalTrials.gov Identifier:
    NCT01190254
    Other Study ID Numbers:
    • P05896
    • 2009-017971-10
    • MK-8274-020
    • CTRI/2011/07/001909
    First Posted:
    Aug 27, 2010
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Organon and Co
    Asenapine
    adolescents
    schizophrenia
    phase IIIb
    placebo-controlled
    Additional relevant MeSH terms:
    Schizophrenia
    Schizophrenia, Disorganized
    Schizophrenia, Paranoid
    Asenapine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually twice daily (BID) for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Period Title: Overall Study
    STARTED 102 98 106
    Treated 102 98 106
    COMPLETED 81 81 84
    NOT COMPLETED 21 17 22

    Baseline Characteristics

    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Total
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period Total of all reporting groups
    Overall Participants 102 98 106 306
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    15.4
    (1.4)
    15.2
    (1.5)
    15.4
    (1.5)
    15.3
    (1.5)
    Sex: Female, Male (Count of Participants)
    Female
    40
    39.2%
    36
    36.7%
    39
    36.8%
    115
    37.6%
    Male
    62
    60.8%
    62
    63.3%
    67
    63.2%
    191
    62.4%
    Positive and Negative Syndrome Scale (PANSS) total score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    97.5
    (10.3)
    97.4
    (10.2)
    98.6
    (13.4)
    97.9
    (11.4)
    Clinical Global Impression of Severity (CGI-S) score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    4.6
    (0.6)
    4.6
    (0.6)
    4.7
    (0.6)
    4.6
    (0.6)
    PANSS positive subscale score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    25.5
    (3.8)
    25.4
    (4.2)
    26.2
    (4.5)
    25.7
    (4.2)
    PANSS negative subscale score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    25.0
    (4.5)
    24.9
    (4.8)
    24.5
    (5.4)
    24.8
    (4.9)
    PANSS positive and negative subscale scores combined (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    50.5
    (5.7)
    50.2
    (5.9)
    50.7
    (7.3)
    50.5
    (6.3)
    PANSS general psychopathology subscale score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    47.1
    (6.4)
    47.2
    (6.0)
    47.9
    (7.7)
    47.4
    (6.8)
    PANSS Marder positive symptoms factor score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    28.4
    (4.0)
    28.7
    (3.6)
    28.9
    (4.3)
    28.7
    (4.0)
    PANSS Marder negative symptoms factor score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    24.2
    (4.8)
    23.9
    (5.4)
    23.8
    (5.9)
    23.9
    (5.4)
    PANSS Marder disorganized thoughts factor score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    22.4
    (3.7)
    22.3
    (3.4)
    22.5
    (4.6)
    22.4
    (3.9)
    PANSS Marder hostility/excitement factor score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    12.9
    (3.5)
    12.8
    (3.6)
    13.1
    (4.3)
    12.9
    (3.8)
    PANSS Marder anxiety/depression factor score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    9.6
    (3.1)
    9.8
    (3.1)
    10.3
    (3.1)
    9.9
    (3.1)
    Children's Global Assessment Scale (CGAS) score - current functioning (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    43.0
    (8.4)
    41.6
    (9.1)
    42.9
    (8.5)
    42.5
    (8.7)
    Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) total score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    41.6
    (10.7)
    41.2
    (10.0)
    40.7
    (9.5)
    41.1
    (10.1)
    PQ-LES-Q overall score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    3.1
    (1.0)
    3.1
    (0.9)
    3.0
    (1.0)
    3.1
    (1.0)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 56
    Description The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy Full Analysis Set [FAS]); also, to be included an on-treatment Day 56 value of PANSS Total Score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 77 72 79
    Mean (Standard Deviation) [score on a scale]
    -17.8
    (17.8)
    -23.7
    (18.6)
    -25.5
    (16.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.070
    Comments p-value is adjusted by Hochberg's method for testing two asenapine groups versus the placebo group
    Method Mixed Model for Repeated Measures (MMRM)
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in Least Squares (LS) Means
    Estimated Value -4.8
    Confidence Interval (2-Sided) 95%
    -9.9 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.064
    Comments p-value is adjusted by Hochberg's method for testing two asenapine groups versus the placebo group
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -5.6
    Confidence Interval (2-Sided) 95%
    -10.7 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID
    Comments Investigation of dose-response relationship of change from baseline to Day 56 in PANSS Total Score was a Secondary study endpoint. Multiple contrast testing using MMRM model was used to evaluate 3 pre-defined dose-response patterns (Linear, Convex, Concave)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.064
    Comments p-value (adjusted to control Type I error in multiple testing) for Linear dose-response pattern (Placebo<2.5 mg<5.0 mg)
    Method MMRM
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID
    Comments Investigation of dose-response relationship of change from baseline to Day 56 in PANSS Total Score was a Secondary study endpoint. Multiple contrast testing using MMRM model was used to evaluate 3 pre-defined dose-response patterns (Linear, Convex, Concave)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.046
    Comments p-value (adjusted to control Type I error in multiple testing) for Convex dose-response pattern (Placebo<2.5 mg=5.0 mg)
    Method MMRM
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID
    Comments Investigation of dose-response relationship of change from baseline to Day 56 in PANSS Total Score was a Secondary study endpoint. Multiple contrast testing using MMRM model was used to evaluate 3 pre-defined dose-response patterns (Linear, Convex, Concave)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.273
    Comments p-value (adjusted to control Type I error in multiple testing) for Concave dose-response pattern (Placebo=2.5 mg<5.0 mg)
    Method MMRM
    Comments
    2. Secondary Outcome
    Title Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Day 56
    Description Change from baseline in CGI-S score at Day 56 is the Key Secondary Outcome Measure. CGI-S is a 7-point scale for assessing the global severity of the participant's illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the CGI-S score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 76 72 79
    Mean (Standard Deviation) [score on a scale]
    -0.8
    (1.1)
    -1.1
    (1.0)
    -1.3
    (1.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Confirmative testing for the key secondary endpoint was to be performed only if both asenapine doses were superior to placebo in change from baseline in PANSS total score at Day 56 (hypotheses associated with Primary outcome measure). If this did not occur, no confirmative testing could be performed and multiplicity unadjusted p-values are provided. Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.218
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Confirmative testing for the key secondary endpoint was to be performed only if both asenapine doses were superior to placebo in change from baseline in PANSS total score at Day 56 (hypotheses associated with Primary outcome measure). If this did not occur, no confirmative testing could be performed and multiplicity unadjusted p-values are provided. Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.024
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.3
    Confidence Interval () 95%
    -0.6 to -0.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    3. Secondary Outcome
    Title Change From Baseline in PANSS Positive Subscale Score at Day 56
    Description This measure reports results for the 7 items of the positive subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive subscale score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS positive subscale score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 77 72 79
    Mean (Standard Deviation) [score on a scale]
    -6.0
    (6.1)
    -7.9
    (5.8)
    -9.1
    (5.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.067
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.6
    Confidence Interval (2-Sided) 95%
    -3.3 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -3.8 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    4. Secondary Outcome
    Title Change From Baseline in PANSS Negative Subscale Score at Day 56
    Description This measure reports results for the 7 items of the negative subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS negative subscale score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS negative subscale score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 77 72 79
    Mean (Standard Deviation) [score on a scale]
    -3.4
    (5.2)
    -4.8
    (5.6)
    -4.9
    (4.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.097
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.6 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.099
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.6 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    5. Secondary Outcome
    Title Change From Baseline in PANSS Positive and Negative Subscale Scores Combined at Day 56
    Description This measure reports results for the combined positive subscale (7 items) and negative subscale (7 items) of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each of the total 14 items in the combined positive and negative subscales, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive and negative subscale scores combined for each participant was calculated as the sum of the rating assigned to each of the 14 combined subscale items, and ranged from 14 to 98 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS positive/negative subscale scores combined must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 77 72 79
    Mean (Standard Deviation) [score on a scale]
    -9.4
    (10.1)
    -12.7
    (10.2)
    -14.0
    (8.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.062
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -2.7
    Confidence Interval (2-Sided) 95%
    -5.6 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.025
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -3.2
    Confidence Interval (2-Sided) 95%
    -6.0 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    6. Secondary Outcome
    Title Change From Baseline in PANSS General Psychopathology Subscale Score at Day 56
    Description This measure reports results for the 16 items of the general psychopathology subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS general psychopathology subscale score for each participant was calculated as the sum of the rating assigned to each of the 16 subscale items, and ranged from 16 to 112 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS general psychopathology subscale score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 77 72 79
    Mean (Standard Deviation) [score on a scale]
    -8.5
    (8.6)
    -10.9
    (9.5)
    -11.5
    (8.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.098
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -4.6 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.071
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -2.3
    Confidence Interval (2-Sided) 95%
    -4.8 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    7. Secondary Outcome
    Title Change From Baseline in PANSS Marder Positive Symptoms Factor Score at Day 56
    Description This measure reports results for the 8 items of the Marder positive symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items (Marder et al. J Clin Psychiatry 1997;58(12):538-46). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder positive symptoms factor score for each participant was calculated as the sum of the rating assigned to each of the 8 applicable Marder factor items, and ranged from 8 to 56 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS Marder positive symptoms factor score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 77 72 79
    Mean (Standard Deviation) [score on a scale]
    -6.1
    (6.1)
    -7.9
    (6.1)
    -8.9
    (5.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.106
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -3.1 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.026
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -3.6 to -0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    8. Secondary Outcome
    Title Change From Baseline in PANSS Marder Negative Symptoms Factor Score at Day 56
    Description This measure reports results for the 7 items of the Marder negative symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder negative symptoms factor score for each participant was calculated as the sum of the rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS Marder negative symptoms factor score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 77 72 79
    Mean (Standard Deviation) [score on a scale]
    -3.7
    (5.3)
    -5.2
    (5.5)
    -5.3
    (4.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.083
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.6 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.067
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -2.7 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    9. Secondary Outcome
    Title Change From Baseline in PANSS Marder Disorganized Thoughts Factor Score at Day 56
    Description This measure reports results for the 7 items of the Marder disorganized thoughts factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder disorganized thoughts factor score for each participant was calculated as the sum of the rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS Marder disorganized thoughts factor score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 77 72 79
    Mean (Standard Deviation) [score on a scale]
    -3.4
    (4.1)
    -4.3
    (4.3)
    -4.8
    (4.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.131
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -2.1 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.135
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -2.1 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    10. Secondary Outcome
    Title Change From Baseline in PANSS Marder Hostility/Excitement Factor Score at Day 56
    Description This measure reports results for the 4 items of the Marder hostility/excitement factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder hostility/excitement factor score for each participant was calculated as the sum of the rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS Marder hostility/excitement factor score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 77 72 79
    Mean (Standard Deviation) [score on a scale]
    -2.8
    (4.0)
    -3.8
    (3.6)
    -3.8
    (4.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.071
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -2.0 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.120
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -1.9 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    11. Secondary Outcome
    Title Change From Baseline in PANSS Marder Anxiety/Depression Factor Score at Day 56
    Description This measure reports results for the 4 items of the Marder anxiety/depression factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder anxiety/depression factor score for each participant was calculated as the sum of the rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS Marder anxiety/depression factor score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 77 72 79
    Mean (Standard Deviation) [score on a scale]
    -1.8
    (2.4)
    -2.4
    (2.9)
    -2.7
    (2.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.263
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -1.2 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.146
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -1.3 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    12. Secondary Outcome
    Title Total PANSS 30% Responders
    Description A Total PANSS 30% responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS Total score at the last available assessment of the study for that participant (i.e., endpoint). The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms.
    Time Frame Baseline up to Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS).
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 100 96 104
    Number [participants]
    36
    35.3%
    48
    49%
    51
    48.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.028
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of (pooled) site, treatment, and baseline PANSS Total Score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.0
    Confidence Interval (2-Sided) 95%
    1.1 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline and (pooled) site. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total PANSS 30% response
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.048
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of (pooled) site, treatment, and baseline PANSS Total Score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.8
    Confidence Interval (2-Sided) 95%
    1.0 to 3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline and (pooled) site. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total PANSS 30% response
    13. Secondary Outcome
    Title Kaplan-Meier Estimate of Cumulative Percentage of Participants With Total PANSS 30% Response at End of Study
    Description A total PANSS 30% response was defined as a reduction from baseline of at least 30% in the PANSS Total score. The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The Kaplan-Meier estimate reports the cumulative percentage of participants with total PANSS 30% response from first drug intake up to approximately Day 59.
    Time Frame Baseline up to approximately Day 59

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS).
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 100 96 104
    Number [cumulative % of participants w/ Response]
    62.0
    60.8%
    64.2
    65.5%
    72.1
    68%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.576
    Comments p-value is for Log Rank test of difference in time to event (PANSS 30% response) curves between the three treatment groups
    Method Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.171
    Comments
    Method Regression, Cox
    Comments Model included factors for (pooled) site, treatment and baseline PANSS Total Score
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    0.9 to 2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments An HR of >1 is considered to mean that asenapine has a higher likelihood of being a Total PANSS 30% Responder than placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.368
    Comments
    Method Regression, Cox
    Comments Model included factors for (pooled) site, treatment and baseline PANSS Total Score
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.2
    Confidence Interval (2-Sided) 95%
    0.8 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments An HR of >1 is considered to mean that asenapine has a higher likelihood of being a Total PANSS 30% Responder than placebo
    14. Secondary Outcome
    Title Clinical Global Impression of Improvement (CGI-I) Score at Day 56
    Description CGI-I is a 7-point scale for assessing the global improvement of the participant's illness relative to baseline, with ratings from 1=very much improved to 7=very much worse.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included an on-treatment Day 56 value of the CGI-I score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 76 72 79
    Mean (Standard Deviation) [score on a scale]
    3.1
    (1.1)
    2.8
    (1.1)
    2.5
    (1.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.094
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, and the interaction of visit by treatment
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, and the interaction of visit by treatment
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -0.8 to -0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    15. Secondary Outcome
    Title CGI-I Responders
    Description A CGI-I responder was defined as a participant who had a CGI-I score of 1 (very much improved) or 2 (much improved) at the last available assessment of the study for that participant (i.e., endpoint). CGI-I is a 7-point scale for assessing the global improvement of the participant's illness relative to baseline, with ratings from 1=very much improved to 7=very much worse.
    Time Frame Baseline up to Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS).
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 100 96 104
    Number [participants]
    28
    27.5%
    36
    36.7%
    41
    38.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.177
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of region (Asia-Pacific, North America, Eastern Europe [Africa/Latin America sites assigned to this region]) and treatment
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.5
    Confidence Interval (2-Sided) 95%
    0.8 to 2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for region. An OR of >1 is considered to mean that asenapine has a higher probability of achieving CGI-I response
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.114
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of region (Asia-Pacific, North America, Eastern Europe [Africa/Latin America sites assigned to this region]) and treatment
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.6
    Confidence Interval (2-Sided) 95%
    0.9 to 2.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for region. An OR of >1 is considered to mean that asenapine has a higher probability of achieving CGI-I response
    16. Secondary Outcome
    Title Kaplan-Meier Estimate of Cumulative Percentage of Participants With CGI-I Response at End of Study
    Description CGI-I response was defined as the occurrence of a CGI-I score of 1 (very much improved) or 2 (much improved). CGI-I is a 7-point scale for assessing the global improvement of the participant's illness relative to baseline, with ratings from 1=very much improved to 7=very much worse. The Kaplan-Meier estimate reports the cumulative percentage of participants with CGI-I response from first drug intake up to approximately Day 58.
    Time Frame Baseline up to approximately Day 58

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS).
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 100 96 104
    Number [cumulative % of participants w/ Response]
    54.7
    53.6%
    47.1
    48.1%
    60.1
    56.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.057
    Comments p-value is for Log Rank test of difference in time to event (CGI-I response) curves between the three treatment groups
    Method Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.135
    Comments
    Method Regression, Cox
    Comments Model included factors for (pooled) site and treatment
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    0.9 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments An HR of >1 is considered to mean that asenapine has a higher likelihood of being a CGI-I Responder than placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    Comments
    Method Regression, Cox
    Comments Model included factors for (pooled) site and treatment
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.8
    Confidence Interval (2-Sided) 95%
    1.2 to 2.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments An HR of >1 is considered to mean that asenapine has a higher likelihood of being a CGI-I Responder than placebo
    17. Secondary Outcome
    Title Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Day 56
    Description CGAS is a 100-point scale measuring psychological, social, and school functioning in children aged 6-17. Minimum scores ranged from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The reported measure is the change from baseline at Day 56; improvement in functioning is represented by positive values.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the CGAS score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 76 72 79
    Mean (Standard Deviation) [score on a scale]
    10.2
    (12.9)
    12.8
    (12.1)
    15.0
    (10.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.417
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    -2.0 to 4.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 100, asenapine 2.5 mg - 96, asenapine - 104)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments
    Method MMRM
    Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 4.2
    Confidence Interval (2-Sided) 95%
    0.8 to 7.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    18. Secondary Outcome
    Title Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 56
    Description PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant was calculated as the sum of the rating assigned to each of the first 14 items, and ranged from 14 to 70 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 56; improvement in quality of life is represented by positive values. This analysis used a last-observation-carried-forward (LOCF) approach; if no Day 56 value was available for a participant, the last available assessment prior to the Day 56 assessment was used.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and at least 1 post-baseline on-treatment value of the PQ-LES-Q total score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 85 83 82
    Mean (Standard Deviation) [score on a scale]
    3.1
    (8.9)
    3.9
    (9.3)
    6.1
    (8.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.600
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment, and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 0.6
    Confidence Interval (2-Sided) 95%
    -1.6 to 2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.064
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment, and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 2.1
    Confidence Interval (2-Sided) 95%
    -0.1 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    19. Secondary Outcome
    Title Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 56
    Description PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The Item 15 result is defined to be the PQ-LES-Q overall score, and ranged from 1 to 5 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 56; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 56 value was available for a participant, the last available assessment prior to the Day 56 assessment was used.
    Time Frame Baseline and Day 56

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and at least 1 post-baseline on-treatment value of the PQ-LES-Q overall score score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    Measure Participants 85 83 82
    Mean (Standard Deviation) [score on a scale]
    0.2
    (1.0)
    0.3
    (1.1)
    0.5
    (0.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.407
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment, and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 0.10
    Confidence Interval (2-Sided) 95%
    -0.13 to 0.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.111
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment, and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 0.19
    Confidence Interval (2-Sided) 95%
    -0.04 to 0.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo

    Adverse Events

    Time Frame Up to 30 days after the last dose of study drug
    Adverse Event Reporting Description
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Arm/Group Description Participants receive placebo asenapine tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
    All Cause Mortality
    Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/102 (2.9%) 3/98 (3.1%) 3/106 (2.8%)
    Infections and infestations
    Pneumonia 0/102 (0%) 0 1/98 (1%) 1 0/106 (0%) 0
    Typhoid fever 0/102 (0%) 0 0/98 (0%) 0 1/106 (0.9%) 1
    Psychiatric disorders
    Schizophrenia 3/102 (2.9%) 3 1/98 (1%) 1 2/106 (1.9%) 2
    Hallucination, auditory 0/102 (0%) 0 1/98 (1%) 1 0/106 (0%) 0
    Other (Not Including Serious) Adverse Events
    Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 23/102 (22.5%) 39/98 (39.8%) 46/106 (43.4%)
    Gastrointestinal disorders
    Nausea 8/102 (7.8%) 9 2/98 (2%) 2 2/106 (1.9%) 2
    Hypoaesthesia oral 1/102 (1%) 1 5/98 (5.1%) 6 5/106 (4.7%) 5
    Nervous system disorders
    Somnolence 7/102 (6.9%) 7 20/98 (20.4%) 22 18/106 (17%) 21
    Headache 6/102 (5.9%) 7 7/98 (7.1%) 12 8/106 (7.5%) 11
    Sedation 2/102 (2%) 2 4/98 (4.1%) 4 12/106 (11.3%) 14
    Akathisia 1/102 (1%) 1 4/98 (4.1%) 5 7/106 (6.6%) 9
    Dizziness 1/102 (1%) 1 7/98 (7.1%) 7 2/106 (1.9%) 5
    Psychiatric disorders
    Insomnia 6/102 (5.9%) 8 5/98 (5.1%) 6 10/106 (9.4%) 12

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    It is planned to first publish/present trial results together with the other sites, unless permission is obtained from Sponsor to publish separate results. Sponsor must be able to review all proposed results communications regarding study 45 days prior to submission for publication/presentation. If there is disagreement concerning appropriateness of the materials, Investigator and Sponsor must meet to make a good faith effort to discuss/resolve disagreement prior to submission for publication.

    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:
    NCT01190254
    Other Study ID Numbers:
    • P05896
    • 2009-017971-10
    • MK-8274-020
    • CTRI/2011/07/001909
    First Posted:
    Aug 27, 2010
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022