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Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder (P06107 Has an Extension [P05898; NCT01349907])(P06107)

Sponsor
Organon and Co (Industry)
Overall Status
Completed
CT.gov ID
NCT01244815
Collaborator
(none)
404
Enrollment
4
Arms
27.1
Actual Duration (Months)

Study Details

Study Description

Brief Summary

Efficacy and safety of asenapine for the treatment of bipolar I disorder (manic or mixed episodes) will be evaluated in participants between 10 and 17 years old, who are either hospitalized or non-hospitalized. In this 3-weeks, double-blind, parallel design trial, eligible participants will be randomized to receive one out of three fixed dose levels of asenapine, or placebo. The study primary hypothesis is that at least one asenapine dose is superior to placebo as measured by the change from baseline to Day 21 in Young Mania Rating Scale (Y-MRS) total score. Trial medication and placebo are provided as identical-looking sublingual tablets; concurrent use of psychotropics is prohibited, except use of short-acting benzodiazepines and psychostimulants approved for the treatment of attention deficit hyperactivity disorder (ADHD). Main treatment effect is measured using Y-MRS and safety is evaluated using the recordings of adverse events, routine blood panels, physical examinations (including vital signs), and electrocardiograms. Participants who complete the double blind trial may be offered to continue (open-label) treatment with asenapine for an extended period of time. Follow-up information on safety parameters will be collected in all participants within 30 days following treatment discontinuation.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Participants' Y-MRS total score at baseline will be subtracted from that at the Day 21 visit to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. The Y-MRS is an 11 item scale: seven items ranked on scale from 0 to 4 and four items ranked 0 to 8 with a range of possible total scores from 0 to 60.

Participants' overall score on the CGI-BP at Day 21 will be evaluated to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. CGI-BP overall score is obtained from a single-item clinician-rated scale used to assess the participant's overall bipolar illness. Scores range from not ill (1) to very severely ill (7).

The proportion of participants whose total Y-MRS score is decreased ≥50% from baseline at Day 4, 7, 14 and 21. Results for the 3 different asenapine doses compared to placebo will be evaluated.

Participants' mania sub-score from the CGI-BP will be evaluated for each study visit (Days 4, 7, 14 and 21) to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated.

Participants' depression sub-score from the CGI-BP will evaluated at each study visit (Days 4, 7, 14 and 21) to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated.

Participants' CDRS-R at baseline will be subtracted from those at each study visit at which this rating was measured (Days 7, 14 and 21) to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. The CDRS-R is a 17-item scale that assesses the presence and severity of depressive symptoms: fourteen items are rated from 1 to 7 and three items are rated from 1 to 5; total scores range from 17 to 113.

Participants' CGAS at baseline will be subtracted from that at the Day 21 visit to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. The CGAS is a 100-point scale, with a possible range of 1 to 100. Normal social functioning is defined as a CGAS total score of ≥70.

Participants' PQ-LES-Q total score at baseline will be subtracted from that at the Day 21 visit to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. The PQ-LES-Q is a 15-item scale, with total score calculated as the sum of the first 14 items, with a range of 14 to 70. Each item is scored by the child from 1 to 5, with higher scores indicative of greater enjoyment and satisfaction.

Participants' PQ-LES-Q overall score (i.e. item 15) at baseline will be subtracted from that at the Day 21 visit to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. The PQ-LES-Q overall score is determined by the answer to item 15 on the questionnaire (range: 1 to 5).

Study Design

Study Type:
Interventional
Actual Enrollment :
404 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Efficacy and Safety of 3-Week Fixed-Dose Asenapine Treatment in Pediatric Acute Manic or Mixed Episodes Associated With Bipolar I Disorder (Protocol No. P06107)
Actual Study Start Date :
Jun 16, 2011
Actual Primary Completion Date :
Aug 28, 2013
Actual Study Completion Date :
Sep 17, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Asenapine 2.5 mg twice daily (BID)

Participants receive asenapine 2.5 mg BID for 21 days.

Drug: asenapine
Asenapine tablets, administered sublingually twice daily at one of three dose levels (2.5 mg, 5.0 mg, or 10.0 mg)
Other Names:
  • SCH 900274, Saphris

    • Drug: Rescue medication
    For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines and EPS medications (i.e., anticholinergics) are allowed. Benadryl (diphenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments.
    Experimental: Asenapine 5.0 mg BID

    Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period.

    Drug: asenapine
    Asenapine tablets, administered sublingually twice daily at one of three dose levels (2.5 mg, 5.0 mg, or 10.0 mg)
    Other Names:
  • SCH 900274, Saphris

    • Drug: Rescue medication
    For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines and EPS medications (i.e., anticholinergics) are allowed. Benadryl (diphenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments.
    Experimental: Asenapine 10.0 mg BID

    Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.

    Drug: asenapine
    Asenapine tablets, administered sublingually twice daily at one of three dose levels (2.5 mg, 5.0 mg, or 10.0 mg)
    Other Names:
  • SCH 900274, Saphris

    • Drug: Rescue medication
    For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines and EPS medications (i.e., anticholinergics) are allowed. Benadryl (diphenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments.
    Placebo Comparator: Placebo

    Participants receive placebo BID for 21 days.

    Drug: Placebo to match asenapine
    Placebo tablets to match asenapine tablets, administered sublingually twice daily

    Drug: Rescue medication
    For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines and EPS medications (i.e., anticholinergics) are allowed. Benadryl (diphenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Y-MRS Total Score at Day 21 [Baseline and Day 21]

      The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight), based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. Seven of the 11 items are rated on a scale of 0-4 and 4 of the items are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.

    Secondary Outcome Measures

    1. Change From Baseline in Clinical Global Impression Scale for Use in Bipolar Disorder (CGI-BP) Overall Score at Day 21 [Baseline and Day 21]

      Change from baseline in CGI-BP overall score at Day 21 is the Key Secondary Outcome Measure. The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the participant's overall bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.

    2. Total Y-MRS 50% Responders at Days 4, 7, 14 and 21 [Baseline and Days 4, 7, 14 and 21]

      A total Y-MRS 50% responder was defined as a participant who had a reduction from baseline to the identified study visit of at least 50% in the Y-MRS total score. The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items, based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60 with higher scores indicating greater severity of symptoms. This analysis used a Last-Observation-Carried-Forward (LOCF) approach; if at a given visit no Y-MRS total score was available for determining whether a participant was a responder, the last available post-baseline on-treatment assessment prior to that visit was used.

    3. Change From Baseline in CGI-BP Mania Score at Day 4 [Baseline and Day 4]

      The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 4; improvement in symptoms is represented by negative values.

    4. Change From Baseline in CGI-BP Mania Score at Day 7 [Baseline and Day 7]

      The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values.

    5. Change From Baseline in CGI-BP Mania Score at Day 14 [Baseline and Day 14]

      The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values.

    6. Change From Baseline in CGI-BP Mania Score at Day 21 [Baseline and Day 21]

      The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.

    7. Change From Baseline in CGI-BP Depression Score at Day 4 [Baseline and Day 4]

      The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 4; improvement in symptoms is represented by negative values.

    8. Change From Baseline in CGI-BP Depression Score at Day 7 [Baseline and Day 7]

      The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values.

    9. Change From Baseline in CGI-BP Depression Score at Day 14 [Baseline and Day 14]

      The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values.

    10. Change From Baseline in CGI-BP Depression Score at Day 21 [Baseline and Day 21]

      The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.

    11. Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score at Day 7 [Baseline and Day 7]

      The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values.

    12. Change From Baseline in CDRS-R Total Score at Day 14 [Baseline and Day 14]

      The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values.

    13. Change From Baseline in CDRS-R Total Score at Day 21 [Baseline and Day 21]

      The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.

    14. Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Day 21 [Baseline and Day 21]

      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 21; improvement in functioning is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used.

    15. Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 21 [Baseline and Day 21]

      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 21; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used.

    16. Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 21 [Baseline and Day 21]

      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 21; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    10 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion criteria:

    • Participants who (or whose parent/legal representative) are able to give written informed consent.

    • Participants must be 10 years of age or older and 17 years of age or younger at the time of treatment assignment (randomization).

    • Participants must have a diagnosis of bipolar I disorder, confirmed by structured interview at screening.

    • Participants must not be pregnant or lactating, and those who are sexually active or become sexually active during the trial, and of child-bearing potential, must be using a medically accepted form of birth control.

    • Participants will be required to have stopped taking certain psycho-active medications prior to baseline.

    • Participants must have a caregiver, or other responsible person living with them who agrees to provide support to the participant to ensure study and procedure compliance.

    Exclusion criteria:

    • Diagnosis of bipolar II disorder, or other form of bipolar or psychotic disorder.

    • Known or suspected mental retardation.

    • Substance abuse, or dependence, within the past 6 months.

    • There is risk of self-harm or harm to others.

    • There is a history of tardive dyskinesia or dystonia.

    • Pregnancy or lactation during the study.

    • History of seizure disorder.

    • Participation in any other clinical trial at the same time.

    • A family member who is part of the study staff or is directly involved with the study.

    • Other medical conditions determined by the study staff to possibly interfere with the study safety and efficacy evaluations.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Organon and Co

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Organon and Co
    ClinicalTrials.gov Identifier:
    NCT01244815
    Other Study ID Numbers:
    • P06107
    First Posted:
    Nov 19, 2010
    Last Update Posted:
    Feb 7, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Organon and Co
    Bi-polar I disorder
    antipsychotic
    serotonin
    dopamine
    noradrenalin
    histamine
    pediatric
    Additional relevant MeSH terms:
    Disease
    Bipolar Disorder
    Asenapine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo twice daily (BID) for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Period Title: Overall Study
    STARTED 101 105 99 99
    Treated 101 104 99 99
    COMPLETED 87 88 88 87
    NOT COMPLETED 14 17 11 12

    Baseline Characteristics

    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID Total
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period. Total of all reporting groups
    Overall Participants 101 104 99 99 403
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    13.7
    (2.0)
    13.7
    (2.1)
    13.8
    (2.0)
    13.9
    (2.1)
    13.8
    (2.0)
    Sex: Female, Male (Count of Participants)
    Female
    63
    62.4%
    52
    50%
    56
    56.6%
    41
    41.4%
    212
    52.6%
    Male
    38
    37.6%
    52
    50%
    43
    43.4%
    58
    58.6%
    191
    47.4%
    Young Mania Rating Scale (Y-MRS) total score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    29.9
    (5.5)
    29.5
    (5.7)
    30.3
    (5.9)
    30.2
    (5.6)
    30.0
    (5.7)
    Clinical Global Impression Scale for use in Bipolar Disorder (CGI-BP) overall score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    4.3
    (0.5)
    4.5
    (0.6)
    4.4
    (0.6)
    4.4
    (0.6)
    4.4
    (0.6)
    CGI-BP mania score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    4.3
    (0.5)
    4.5
    (0.6)
    4.4
    (0.6)
    4.4
    (0.6)
    4.4
    (0.6)
    CGI-BP depression score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    2.9
    (1.3)
    2.8
    (1.3)
    2.9
    (1.4)
    2.8
    (1.2)
    2.8
    (1.3)
    Children's Depression Rating Scale, Revised (CDRS-R) total score (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    34.5
    (10.2)
    33.7
    (9.0)
    35.2
    (11.9)
    34.1
    (9.0)
    34.4
    (10.1)
    Children's Global Assessment Scale (CGAS) total score - current functioning (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    49.0
    (7.9)
    49.6
    (7.4)
    48.4
    (7.4)
    49.1
    (6.7)
    49.0
    (7.4)
    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]
    48.7
    (9.7)
    49.1
    (9.6)
    49.5
    (9.1)
    49.1
    (10.5)
    49.1
    (9.7)
    PQ-LES-Q overall score (i.e., item 15) (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    3.7
    (1.0)
    3.8
    (1.0)
    3.8
    (0.9)
    3.8
    (1.0)
    3.8
    (1.0)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Y-MRS Total Score at Day 21
    Description The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight), based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. Seven of the 11 items are rated on a scale of 0-4 and 4 of the items are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 21

    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 Y-MRS total score (this group is termed the efficacy Full Analysis Set [FAS]); also, to be included an on-treatment Day 21 value of Y-MRS total score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 79 88 87 81
    Mean (Standard Deviation) [score on a scale]
    -9.6
    (7.8)
    -12.3
    (9.0)
    -15.1
    (9.5)
    -15.9
    (9.1)
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments p-value is adjusted by Hochberg's method for testing three 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 -3.2
    Confidence Interval (2-Sided) 95%
    -5.6 to -0.8
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments p-value is adjusted by Hochberg's method for testing three 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 -5.3
    Confidence Interval (2-Sided) 95%
    -7.7 to -2.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments p-value is adjusted by Hochberg's method for testing three 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 -6.2
    Confidence Interval (2-Sided) 95%
    -8.6 to -3.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
    Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 1 (Placebo<2.5 mg=5.0 mg=10.0 mg)
    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 t-statistic
    Estimated Value -4.92
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 1. Lower value indicates pattern provides better fit to data.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
    Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 2 (Placebo=2.5 mg<5.0 mg=10.0 mg)
    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 t-statistic
    Estimated Value -4.87
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 2. Lower value indicates pattern provides better fit to data.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
    Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0021
    Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 3 (Placebo=2.5 mg=5.0 mg<10.0 mg)
    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 t-statistic
    Estimated Value -3.40
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 3. Lower value indicates pattern provides better fit to data.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
    Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 4 (Placebo<2.5 mg<5.0 mg<10.0 mg)
    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 t-statistic
    Estimated Value -5.28
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 4. Lower value indicates pattern provides better fit to data.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
    Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 5 (Placebo=2.5 mg<5.0 mg<10.0 mg)
    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 t-statistic
    Estimated Value -4.64
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 5. Lower value indicates pattern provides better fit to data.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
    Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 6 (Placebo<2.5 mg=5.0 mg<10.0 mg)
    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 t-statistic
    Estimated Value -5.07
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 6. Lower value indicates pattern provides better fit to data.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
    Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 7 (Placebo<2.5 mg<5.0 mg=10.0 mg)
    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 t-statistic
    Estimated Value -5.49
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 7. Lower value indicates pattern provides better fit to data.
    2. Secondary Outcome
    Title Change From Baseline in Clinical Global Impression Scale for Use in Bipolar Disorder (CGI-BP) Overall Score at Day 21
    Description Change from baseline in CGI-BP overall score at Day 21 is the Key Secondary Outcome Measure. The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the participant's overall bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 21

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CGI-BP overall score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 79 88 87 81
    Mean (Standard Deviation) [score on a scale]
    -0.7
    (0.9)
    -1.3
    (1.1)
    -1.4
    (1.0)
    -1.4
    (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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments p-value is adjusted by Hochberg's method for testing three 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 -0.6
    Confidence Interval (2-Sided) 95%
    -0.9 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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments p-value is adjusted by Hochberg's method for testing three 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 -0.7
    Confidence Interval (2-Sided) 95%
    -0.9 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments p-value is adjusted by Hochberg's method for testing three 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 -0.7
    Confidence Interval (2-Sided) 95%
    -1.0 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    3. Secondary Outcome
    Title Total Y-MRS 50% Responders at Days 4, 7, 14 and 21
    Description A total Y-MRS 50% responder was defined as a participant who had a reduction from baseline to the identified study visit of at least 50% in the Y-MRS total score. The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items, based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60 with higher scores indicating greater severity of symptoms. This analysis used a Last-Observation-Carried-Forward (LOCF) approach; if at a given visit no Y-MRS total score was available for determining whether a participant was a responder, the last available post-baseline on-treatment assessment prior to that visit was used.
    Time Frame Baseline and Days 4, 7, 14 and 21

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included for a visit, a Y-MRS total score must be available for that visit or a prior post-baseline on-treatment visit
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 98 101 98 98
    Day 4 (n=95, 98, 93, 90)
    7
    6.9%
    19
    18.3%
    20
    20.2%
    13
    13.1%
    Day 7 (n=98, 101, 98, 98)
    14
    13.9%
    33
    31.7%
    31
    31.3%
    37
    37.4%
    Day 14 (n=98, 101, 98, 98)
    20
    19.8%
    36
    34.6%
    50
    50.5%
    50
    50.5%
    Day 21 (n=98, 101, 98, 98)
    27
    26.7%
    42
    40.4%
    53
    53.5%
    51
    51.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Analysis is for asenapine versus placebo on Day 4 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.0
    Confidence Interval (2-Sided) 95%
    1.2 to 7.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Analysis is for asenapine versus placebo on Day 4 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.4
    Confidence Interval (2-Sided) 95%
    1.4 to 8.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Analysis is for asenapine versus placebo on Day 4 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.129
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.1
    Confidence Interval (2-Sided) 95%
    0.8 to 5.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Analysis is for asenapine versus placebo on Day 7 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.9
    Confidence Interval (2-Sided) 95%
    1.4 to 5.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Analysis is for asenapine versus placebo on Day 7 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.8
    Confidence Interval (2-Sided) 95%
    1.4 to 5.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Analysis is for asenapine versus placebo on Day 7 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.6
    Confidence Interval (2-Sided) 95%
    1.8 to 7.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Analysis is for asenapine versus placebo on Day 14 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.2
    Confidence Interval (2-Sided) 95%
    1.1 to 4.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Analysis is for asenapine versus placebo on Day 14 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.1
    Confidence Interval (2-Sided) 95%
    2.2 to 7.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Analysis is for asenapine versus placebo on Day 14 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.1
    Confidence Interval (2-Sided) 95%
    2.2 to 7.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
    Comments Analysis is for asenapine versus placebo on Day 21 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.042
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.9
    Confidence Interval (2-Sided) 95%
    1.0 to 3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
    Comments Analysis is for asenapine versus placebo on Day 21 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.2
    Confidence Interval (2-Sided) 95%
    1.7 to 5.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Analysis is for asenapine versus placebo on Day 21 (LOCF)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments 95% Confidence Interval and p-value are based on Wald statistic
    Method Regression, Logistic
    Comments Model included terms of treatment and baseline Y-MRS total score
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.9
    Confidence Interval () 95%
    1.6 to 5.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
    4. Secondary Outcome
    Title Change From Baseline in CGI-BP Mania Score at Day 4
    Description The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 4; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 4

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 4 value of CGI-BP mania score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 93 97 93 90
    Mean (Standard Deviation) [score on a scale]
    -0.3
    (0.6)
    -0.6
    (0.8)
    -0.5
    (0.7)
    -0.5
    (0.8)
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.014
    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 -0.25
    Confidence Interval (2-Sided) 95%
    -0.45 to -0.05
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.107
    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 -0.17
    Confidence Interval (2-Sided) 95%
    -0.37 to 0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.039
    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 -0.21
    Confidence Interval (2-Sided) 95%
    -0.42 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    5. Secondary Outcome
    Title Change From Baseline in CGI-BP Mania Score at Day 7
    Description The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 7

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 7 value of CGI-BP mania score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 95 98 95 97
    Mean (Standard Deviation) [score on a scale]
    -0.5
    (0.7)
    -0.9
    (0.9)
    -0.9
    (1.0)
    -0.9
    (0.9)
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    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 -0.33
    Confidence Interval (2-Sided) 95%
    -0.56 to -0.10
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    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, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.35
    Confidence Interval (2-Sided) 95%
    -0.59 to -0.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    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 -0.44
    Confidence Interval (2-Sided) 95%
    -0.67 to -0.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    6. Secondary Outcome
    Title Change From Baseline in CGI-BP Mania Score at Day 14
    Description The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 14

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 14 value of CGI-BP mania score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 89 91 90 91
    Mean (Standard Deviation) [score on a scale]
    -0.6
    (1.0)
    -1.1
    (1.0)
    -1.4
    (1.0)
    -1.3
    (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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    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 -0.34
    Confidence Interval (2-Sided) 95%
    -0.61 to -0.08
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    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 -0.63
    Confidence Interval (2-Sided) 95%
    -0.89 to -0.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    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 -0.61
    Confidence Interval (2-Sided) 95%
    -0.88 to -0.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    7. Secondary Outcome
    Title Change From Baseline in CGI-BP Mania Score at Day 21
    Description The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 21

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CGI-BP mania score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 79 88 87 81
    Mean (Standard Deviation) [score on a scale]
    -0.7
    (0.9)
    -1.3
    (1.1)
    -1.5
    (1.1)
    -1.4
    (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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    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 -0.61
    Confidence Interval (2-Sided) 95%
    -0.90 to -0.32
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    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 -0.75
    Confidence Interval (2-Sided) 95%
    -1.04 to -0.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    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 -0.74
    Confidence Interval (2-Sided) 95%
    -1.03 to -0.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    8. Secondary Outcome
    Title Change From Baseline in CGI-BP Depression Score at Day 4
    Description The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 4; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 4

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 4 value of CGI-BP depression score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 92 97 93 90
    Mean (Standard Deviation) [score on a scale]
    -0.2
    (0.7)
    -0.3
    (0.8)
    -0.2
    (1.0)
    -0.1
    (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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.536
    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 -0.07
    Confidence Interval (2-Sided) 95%
    -0.28 to 0.15
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.811
    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 -0.03
    Confidence Interval (2-Sided) 95%
    -0.24 to 0.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.556
    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 0.07
    Confidence Interval (2-Sided) 95%
    -0.15 to 0.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    9. Secondary Outcome
    Title Change From Baseline in CGI-BP Depression Score at Day 7
    Description The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 7

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 7 value of CGI-BP depression score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 94 98 95 97
    Mean (Standard Deviation) [score on a scale]
    -0.4
    (0.9)
    -0.5
    (0.8)
    -0.5
    (1.1)
    -0.5
    (0.9)
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    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 -0.21
    Confidence Interval (2-Sided) 95%
    -0.42 to 0.00
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    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, baseline, and the interaction of visit by treatment and baseline by visit
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.18
    Confidence Interval (2-Sided) 95%
    -0.40 to 0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.178
    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 -0.15
    Confidence Interval (2-Sided) 95%
    -0.36 to 0.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    10. Secondary Outcome
    Title Change From Baseline in CGI-BP Depression Score at Day 14
    Description The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 14

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 14 value of CGI-BP depression score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 88 91 90 91
    Mean (Standard Deviation) [score on a scale]
    -0.5
    (1.1)
    -0.5
    (1.0)
    -0.7
    (1.0)
    -0.6
    (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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.506
    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 -0.08
    Confidence Interval (2-Sided) 95%
    -0.33 to 0.16
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    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 -0.19
    Confidence Interval (2-Sided) 95%
    -0.43 to 0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.211
    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 -0.16
    Confidence Interval (2-Sided) 95%
    -0.40 to 0.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    11. Secondary Outcome
    Title Change From Baseline in CGI-BP Depression Score at Day 21
    Description The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 21

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CGI-BP depression score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 78 88 87 81
    Mean (Standard Deviation) [score on a scale]
    -0.4
    (1.0)
    -0.6
    (1.1)
    -0.8
    (1.1)
    -0.6
    (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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.079
    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 -0.23
    Confidence Interval (2-Sided) 95%
    -0.49 to 0.03
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    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 -0.34
    Confidence Interval (2-Sided) 95%
    -0.60 to -0.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.139
    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 -0.20
    Confidence Interval (2-Sided) 95%
    -0.46 to 0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    12. Secondary Outcome
    Title Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score at Day 7
    Description The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 7

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 7 value of CDRS-R total score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 94 95 91 95
    Mean (Standard Deviation) [score on a scale]
    -4.1
    (8.1)
    -6.1
    (7.1)
    -6.1
    (8.0)
    -5.9
    (8.5)
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    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 -2.61
    Confidence Interval (2-Sided) 95%
    -4.38 to -0.83
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    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 -2.17
    Confidence Interval (2-Sided) 95%
    -3.95 to -0.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    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 -2.16
    Confidence Interval (2-Sided) 95%
    -3.93 to -0.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    13. Secondary Outcome
    Title Change From Baseline in CDRS-R Total Score at Day 14
    Description The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 14

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 14 value of CDRS-R total score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 88 89 90 90
    Mean (Standard Deviation) [score on a scale]
    -5.5
    (8.1)
    -5.8
    (6.5)
    -8.7
    (10.5)
    -6.6
    (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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.395
    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 -0.79
    Confidence Interval (2-Sided) 95%
    -2.62 to 1.04
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    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 -2.44
    Confidence Interval (2-Sided) 95%
    -4.26 to -0.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.121
    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 -1.44
    Confidence Interval (2-Sided) 95%
    -3.27 to 0.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    14. Secondary Outcome
    Title Change From Baseline in CDRS-R Total Score at Day 21
    Description The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.
    Time Frame Baseline and Day 21

    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 Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CDRS-R total score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 78 87 87 81
    Mean (Standard Deviation) [score on a scale]
    -6.1
    (8.8)
    -6.9
    (7.3)
    -8.7
    (11.4)
    -6.8
    (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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    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 -1.44
    Confidence Interval (2-Sided) 95%
    -3.33 to 0.45
    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 - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.023
    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 -2.19
    Confidence Interval (2-Sided) 95%
    -4.08 to -0.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98)
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.189
    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 -1.28
    Confidence Interval (2-Sided) 95%
    -3.20 to 0.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    15. Secondary Outcome
    Title Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Day 21
    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 21; improvement in functioning is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used.
    Time Frame Baseline and Day 21

    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 Y-MRS 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 CGAS score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 84 93 91 85
    Mean (Standard Deviation) [score on a scale]
    6.0
    (8.1)
    9.4
    (9.5)
    13.0
    (11.6)
    10.8
    (9.7)
    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 0.002
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 4.29
    Confidence Interval (2-Sided) 95%
    1.56 to 7.02
    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 <0.001
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 6.95
    Confidence Interval (2-Sided) 95%
    4.22 to 9.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 5.11
    Confidence Interval (2-Sided) 95%
    2.31 to 7.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    16. Secondary Outcome
    Title Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 21
    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 21; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used.
    Time Frame Baseline and Day 21

    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 Y-MRS 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 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 Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 84 92 90 84
    Mean (Standard Deviation) [score on a scale]
    1.5
    (8.2)
    3.7
    (8.6)
    2.5
    (10.8)
    4.0
    (9.8)
    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 0.050
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 2.24
    Confidence Interval (2-Sided) 95%
    -0.00 to 4.48
    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 0.239
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 1.35
    Confidence Interval (2-Sided) 95%
    -0.90 to 3.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 2.78
    Confidence Interval (2-Sided) 95%
    0.48 to 5.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    17. Secondary Outcome
    Title Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 21
    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 21; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used.
    Time Frame Baseline and Day 21

    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 Y-MRS 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 PQ-LES-Q overall score must be available for a participant.
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    Measure Participants 84 92 90 84
    Mean (Standard Deviation) [score on a scale]
    -0.0
    (0.9)
    0.4
    (1.0)
    0.1
    (1.0)
    0.2
    (1.1)
    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 0.001
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 0.39
    Confidence Interval (2-Sided) 95%
    0.15 to 0.62
    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 0.135
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 0.18
    Confidence Interval (2-Sided) 95%
    -0.06 to 0.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments Estimate is asenapine versus placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.044
    Comments
    Method ANCOVA
    Comments Model included terms of (pooled) site, treatment and baseline
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 0.25
    Confidence Interval (2-Sided) 95%
    0.01 to 0.49
    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 (Up to 51 days)
    Adverse Event Reporting Description
    Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg 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 asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
    All Cause Mortality
    Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/101 (3%) 0/104 (0%) 2/99 (2%) 2/99 (2%)
    Psychiatric disorders
    BIPOLAR DISORDER 1/101 (1%) 1 0/104 (0%) 0 0/99 (0%) 0 1/99 (1%) 1
    BIPOLAR I DISORDER 1/101 (1%) 1 0/104 (0%) 0 1/99 (1%) 1 0/99 (0%) 0
    MANIA 0/101 (0%) 0 0/104 (0%) 0 1/99 (1%) 1 0/99 (0%) 0
    SUICIDAL BEHAVIOUR 1/101 (1%) 1 0/104 (0%) 0 0/99 (0%) 0 0/99 (0%) 0
    SUICIDAL IDEATION 1/101 (1%) 1 0/104 (0%) 0 0/99 (0%) 0 0/99 (0%) 0
    SUICIDE ATTEMPT 0/101 (0%) 0 0/104 (0%) 0 0/99 (0%) 0 1/99 (1%) 1
    Other (Not Including Serious) Adverse Events
    Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 30/101 (29.7%) 68/104 (65.4%) 70/99 (70.7%) 72/99 (72.7%)
    Gastrointestinal disorders
    ABDOMINAL PAIN UPPER 6/101 (5.9%) 6 5/104 (4.8%) 5 2/99 (2%) 2 3/99 (3%) 3
    HYPOAESTHESIA ORAL 2/101 (2%) 2 18/104 (17.3%) 18 18/99 (18.2%) 19 20/99 (20.2%) 21
    NAUSEA 3/101 (3%) 3 6/104 (5.8%) 6 6/99 (6.1%) 6 6/99 (6.1%) 7
    PARAESTHESIA ORAL 2/101 (2%) 2 9/104 (8.7%) 9 9/99 (9.1%) 9 11/99 (11.1%) 11
    General disorders
    FATIGUE 5/101 (5%) 5 4/104 (3.8%) 4 8/99 (8.1%) 8 13/99 (13.1%) 13
    Investigations
    WEIGHT INCREASED 0/101 (0%) 0 6/104 (5.8%) 6 2/99 (2%) 2 2/99 (2%) 2
    Metabolism and nutrition disorders
    INCREASED APPETITE 2/101 (2%) 2 10/104 (9.6%) 10 9/99 (9.1%) 10 6/99 (6.1%) 6
    Nervous system disorders
    DIZZINESS 3/101 (3%) 4 6/104 (5.8%) 6 10/99 (10.1%) 11 5/99 (5.1%) 5
    DYSGEUSIA 2/101 (2%) 2 4/104 (3.8%) 4 5/99 (5.1%) 5 9/99 (9.1%) 9
    HEADACHE 6/101 (5.9%) 6 8/104 (7.7%) 11 11/99 (11.1%) 12 9/99 (9.1%) 10
    SEDATION 5/101 (5%) 5 16/104 (15.4%) 16 19/99 (19.2%) 19 18/99 (18.2%) 20
    SOMNOLENCE 6/101 (5.9%) 6 34/104 (32.7%) 39 34/99 (34.3%) 36 31/99 (31.3%) 34

    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:
    NCT01244815
    Other Study ID Numbers:
    • P06107
    First Posted:
    Nov 19, 2010
    Last Update Posted:
    Feb 7, 2022
    Last Verified:
    Feb 1, 2022