Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Multicenter, Double-Blind, Fixed-Dose, Long-Term Extension Trial of the Safety of Asenapine in Subjects Diagnosed with Bipolar 1 Disorder who Completed Protocol P05691 (formerly 041044) (Phase 3B, Protocol P05692 [formerly 041045])

    Summary
    EudraCT number
    		 2010-018410-78
    Trial protocol
    		 BG  
    Global end of trial date
    03 Dec 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Jan 2019
    First version publication date
    31 Jan 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    P05692
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01395992
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Forest Research Institute, Inc., an affiliate of Allergan, plc
    Sponsor organisation address
    185 Hudson Street, Jersey City, United States, NJ 07302
    Public contact
    Willie Earley, Forest Research Institute, Inc., an affiliate of Allergan, plc, Willie.Earley@Allergan.com
    Scientific contact
    Willie Earley, Forest Research Institute, Inc., an affiliate of Allergan, plc, Willie.Earley@Allergan.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Dec 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Dec 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Dec 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this trial was to evaluate the long-term safety of asenapine in participants diagnosed with Bipolar 1 Disorder. Participants received a fixed dose of asenapine (either 5 or 10 milligram [mg] twice daily [BID]) for 26 weeks.
    Protection of trial subjects
    This trial was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 This was a long-term extension trial for participants who had completed the 3-week short-term trial P05691. In the previous short-term trial, participants had been randomly assigned to receive a fixed dose of asenapine (either 5 mg or 10 mg BID) or placebo (BID) for 3 weeks.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 May 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 125
    Country: Number of subjects enrolled
    Bulgaria: 20
    Country: Number of subjects enrolled
    Ukraine: 14
    Country: Number of subjects enrolled
    Russian Federation: 4
    Country: Number of subjects enrolled
    Croatia: 2
    Worldwide total number of subjects
    165
    EEA total number of subjects
    22
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    162
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 First participant enrolled: 9 May 2012; last participant completed: 3 Dec 2014. This trial was performed at 38 sites across the United States, Bulgaria, Ukraine, the Russian Federation, and Croatia.

    Pre-assignment
    Screening details
    		 A total of 165 participants who had previously completed the short-term randomized trial P05691 continued in the current extension trial (P05692). Participants randomly assigned to asenapine in P05691 were assigned the same treatment regimen in P05692; participants randomly assigned to placebo were assigned to asenapine 5 mg BID.

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Placebo / Asenapine 5 mg
    Arm description
    		 In the previous short-term trial PO5691, participants were administered placebo BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks.
    Arm type
    		 Experimental

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

    Arm title
    		 Asenapine 5 mg / Asenapine 5 mg
    Arm description
    		 In the previous short-term trial PO5691, participants were administered one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 5 mg asenapine tablet BID) for 26 weeks.
    Arm type
    		 Experimental

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

    Arm title
    		 Asenapine 5 mg Overall
    Arm description
    		 In the previous short-term trial PO5691, participants were administered either placebo BID or one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks. The 'asenapine 5 mg overall' arm represents the 'placebo / asenapine 5 mg' and 'asenapine 5 mg / asenapine 5 mg' arms combined.
    Arm type
    		 Experimental

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

    Arm title
    		 Asenapine 10 mg / Asenapine 10 mg
    Arm description
    		 In the previous short-term trial PO5691, participants were administered one 10 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 10 mg asenapine tablet BID) for 26 weeks.
    Arm type
    		 Experimental

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

    Number of subjects in period 1
    		Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 5 mg Overall Asenapine 10 mg / Asenapine 10 mg
    Started
    61
    53
    114
    51
    Completed
    60
    53
    113
    51
    Not completed
    1
    0
    1
    0
         Did not meet protocol eligibility (not treated)
    1
    -
    1
    -
    Period 2
    Period 2 title
    Treatment through Trial Completion
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Placebo / Asenapine 5 mg
    Arm description
    		 In the previous short-term trial PO5691, participants were administered placebo BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks.
    Arm type
    		 Experimental

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

    Arm title
    		 Asenapine 5 mg / Asenapine 5 mg
    Arm description
    		 In the previous short-term trial PO5691, participants were administered one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 5 mg asenapine tablet BID) for 26 weeks.
    Arm type
    		 Experimental

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

    Arm title
    		 Asenapine 5 mg Overall
    Arm description
    		 In the previous short-term trial PO5691, participants were administered either placebo BID or one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks. The 'asenapine 5 mg overall' arm represents the 'placebo / asenapine 5 mg' and 'asenapine 5 mg / asenapine 5 mg' arms combined.
    Arm type
    		 Experimental

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

    Arm title
    		 Asenapine 10 mg / Asenapine 10 mg
    Arm description
    		 In the previous short-term trial PO5691, participants were administered one 10 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 10 mg asenapine tablet BID) for 26 weeks.
    Arm type
    		 Experimental

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

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: The participants who started Period 1 are those enrolled in this extension trial PO5692, 1 of whom did not receive study drug. The participants who started Period 2 are those who received study drug. The baseline demographics table presents data for participants treated, therefore Period 2 was set as the baseline period.
    Number of subjects in period 2
    		Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 5 mg Overall Asenapine 10 mg / Asenapine 10 mg
    Started
    60
    53
    113
    51
    Completed
    49
    45
    94
    46
    Not completed
    11
    8
    19
    5
         Consent withdrawn by subject
    2
    2
    4
    4
         Adverse event, non-fatal
    1
    1
    2
    -
         Lost to follow-up
    6
    5
    11
    1
         Protocol deviation
    2
    -
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups [1]
    Reporting group title
    Placebo / Asenapine 5 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered placebo BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks.

    Reporting group title
    Asenapine 5 mg / Asenapine 5 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 5 mg asenapine tablet BID) for 26 weeks.

    Reporting group title
    Asenapine 5 mg Overall
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered either placebo BID or one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks. The 'asenapine 5 mg overall' arm represents the 'placebo / asenapine 5 mg' and 'asenapine 5 mg / asenapine 5 mg' arms combined.

    Reporting group title
    Asenapine 10 mg / Asenapine 10 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered one 10 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 10 mg asenapine tablet BID) for 26 weeks.

    Notes
    [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The worldwide number enrolled in the trial presents participants who continued in this extension trial PO5692 from the previous short-term trial PO5691 ; 1 of these participants did not receive study drug. The participants who started Period 2 ("baseline period") are those who received study drug. The baseline demographics table presents data for participants treated, therefore Period 2 was set as the baseline period.
    Reporting group values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 5 mg Overall Asenapine 10 mg / Asenapine 10 mg Total
    Number of subjects
    		 60 53 113 51
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 43.9 ( 10.9 ) 44.8 ( 9.55 ) 44.4 ( 10.25 ) 44.6 ( 10.66 ) -
    Gender Categorical
    Units: Subjects
        Male
    		 28 25 53 22 128
        Female
    		 32 28 60 29 149

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo / Asenapine 5 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered placebo BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks.

    Reporting group title
    Asenapine 5 mg / Asenapine 5 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 5 mg asenapine tablet BID) for 26 weeks.

    Reporting group title
    Asenapine 5 mg Overall
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered either placebo BID or one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks. The 'asenapine 5 mg overall' arm represents the 'placebo / asenapine 5 mg' and 'asenapine 5 mg / asenapine 5 mg' arms combined.

    Reporting group title
    Asenapine 10 mg / Asenapine 10 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered one 10 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 10 mg asenapine tablet BID) for 26 weeks.
    Reporting group title
    Placebo / Asenapine 5 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered placebo BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks.

    Reporting group title
    Asenapine 5 mg / Asenapine 5 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 5 mg asenapine tablet BID) for 26 weeks.

    Reporting group title
    Asenapine 5 mg Overall
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered either placebo BID or one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks. The 'asenapine 5 mg overall' arm represents the 'placebo / asenapine 5 mg' and 'asenapine 5 mg / asenapine 5 mg' arms combined.

    Reporting group title
    Asenapine 10 mg / Asenapine 10 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered one 10 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 10 mg asenapine tablet BID) for 26 weeks.

    Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    		 Close Top of page
    End point title
    		 Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [1]
    End point description
    TEAEs were adverse events (AEs) which were first reported or worsened in severity on or after the first dose of study drug in the current extension trial (P05692) through: last dose date plus 7 days (for non-serious AEs) or last dose date plus 30 days (for Serious adverse events [SAEs]). The reported measure is the number of participants with ≥1 TEAE (and sub-categorised into treatment related TEAEs and severe TEAEs). Population for this analysis was the All Treated Set (ATS), defined as all randomized participants from the short-term trial (PO5691) who received ≥1 dose study drug in the current extension trial (P05692).
    End point type
    Primary
    End point timeframe
    Baseline up to 30 days after last dose of study drug (up to approximately 30 weeks)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was performed for the end point "Number of Participants With Treatment-Emergent Adverse Events (TEAEs)".
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 5 mg Overall Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    60
    53
    113
    51
    Units: Participants
        TEAE
    41
    29
    70
    26
        Treatment related TEAE
    28
    15
    43
    15
        Severe TEAE
    3
    2
    5
    3
    No statistical analyses for this end point

    Secondary: Change from Trial P05691 Baseline in Young-Mania Rating Scale (Y-MRS) Total Score at Days 7, 28, 84, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 Change from Trial P05691 Baseline in Young-Mania Rating Scale (Y-MRS) Total Score at Days 7, 28, 84, 182, and Study Endpoint
    End point description
    Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-agressive behavior. The scores from the 11 items are summed to give a Total Score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The reported measure is the change from short-term trial baseline (P05691) at each specified visit, analysed using an analysis of covariance (ANCOVA) model including fixed effects for treatment and investigative site (or pooled site) and baseline value as a covariate; improvement in symptoms is represented by negative values. Population for this analysis was the Full Analysis Set (FAS), defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Baseline (P05691) and Days 7, 28, 84, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    least squares mean (standard error)
        Day 7 (n=56, 48, 50)
    -17.7 ( 1.13 )
    -18.9 ( 1.22 )
    -20.3 ( 1.2 )
        Day 28 (n=47, 36, 38)
    -19.4 ( 0.95 )
    -21.8 ( 1.12 )
    -23.4 ( 1.07 )
        Day 84 (n=38, 33, 33)
    -21.5 ( 0.87 )
    -22.4 ( 0.98 )
    -23.5 ( 0.96 )
        Day 182 (n=32, 27, 23)
    -22.7 ( 0.93 )
    -24.7 ( 1.06 )
    -23.5 ( 1.06 )
        Study Endpoint (n=57, 50, 50)
    -22.3 ( 0.94 )
    -22.9 ( 1.01 )
    -22 ( 1.01 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants who are Y-MRS Responders at Days 7, 28, 84, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 Percentage of Participants who are Y-MRS Responders at Days 7, 28, 84, 182, and Study Endpoint
    End point description
    A Y-MRS responder was defined as a participant who had a reduction from baseline of at least 50% in the Y-MRS Total Score at a post-baseline assessment. Responder status was assessed relative to the short-term trial baseline (P05691). Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behaviour. The scores from the 11 items are summed to give a Total Score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 28, 84, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: Percentage of responders
    number (not applicable)
        Day 7 (n=56, 48, 50)
    66.1
    68.8
    80
        Day 28 (n=47, 36, 38)
    72.3
    86.1
    92.1
        Day 84 (n=38, 33, 33)
    92.1
    84.8
    93.9
        Day 182 (n=32, 27, 23)
    90.6
    96.3
    91.3
        Study Endpoint (n=57, 50, 50)
    87.7
    88
    84
    No statistical analyses for this end point

    Secondary: Percentage of Participants who are Y-MRS Remitters at Days 7, 28, 84, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 Percentage of Participants who are Y-MRS Remitters at Days 7, 28, 84, 182, and Study Endpoint
    End point description
    A Y-MRS remitter was defined as a participant who had a Total Score of 12 or lower at a post-baseline assessment. Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-agressive behavior. The scores from the 11 items are summed to give a Total Score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 28, 84, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: Percentage of participants
    number (not applicable)
        Day 7 (n=56, 48, 50)
    55.4
    62.5
    62
        Day 28 (n=47, 36, 38)
    59.6
    83.3
    86.8
        Day 84 (n=38, 33, 33)
    73.7
    81.8
    72.7
        Day 182 (n=32, 27, 23)
    81.3
    96.3
    78.3
        Study Endpoint (n=57, 50, 50)
    77.2
    86
    68
    No statistical analyses for this end point

    Secondary: Change from Trial P05691 Baseline in Clinical Global Impression – Bipolar Mania – Severity of Illness (CGI-BP-S) Overall Score at Days 7, 14, 28, 56, 84, 112, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 Change from Trial P05691 Baseline in Clinical Global Impression – Bipolar Mania – Severity of Illness (CGI-BP-S) Overall Score at Days 7, 14, 28, 56, 84, 112, 182, and Study Endpoint
    End point description
    The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The reported measure is the change from short-term trial baseline (P05691) at each specified visit, analysed using an ANCOVA model including fixed effects for treatment and investigative site (or pooled site) and baseline value as a covariate; improvement in symptoms is represented by negative values. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 7, 14, 28, 56, 84, 112, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    least squares mean (standard error)
        Day 7 (n=56, 48, 50)
    -1.9 ( 0.15 )
    -2 ( 0.16 )
    -2.1 ( 0.16 )
        Day 14 (n=53, 44, 43)
    -1.9 ( 0.14 )
    -2.2 ( 0.16 )
    -2.3 ( 0.16 )
        Day 28 (n=47, 36, 37)
    -2.1 ( 0.14 )
    -2.3 ( 0.17 )
    -2.2 ( 0.16 )
        Day 56 (n=42, 36, 35)
    -2.3 ( 0.13 )
    -2.6 ( 0.15 )
    -2.2 ( 0.15 )
        Day 84 (n=38, 33, 33)
    -2.2 ( 0.15 )
    -2.5 ( 0.17 )
    -2.3 ( 0.17 )
        Day 112 (n=36, 25, 28)
    -2.3 ( 0.16 )
    -2.5 ( 0.19 )
    -2.6 ( 0.18 )
        Day 182 (n=32, 27, 23)
    -2.6 ( 0.18 )
    -2.7 ( 0.2 )
    -2.8 ( 0.21 )
        Study Endpoint (n=57, 50, 50)
    -2.3 ( 0.16 )
    -2.4 ( 0.16 )
    -2.3 ( 0.17 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants who are Clinical Global Impression – Bipolar Mania – Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score at Days 7, 14, 28, 56, 84, 112, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 Percentage of Participants who are Clinical Global Impression – Bipolar Mania – Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score at Days 7, 14, 28, 56, 84, 112, 182, and Study Endpoint
    End point description
    A CGI-BP-I (Overall Bipolar Illness) responder was defined as a participant who had a score of 3 (minimally improved) or lower at a post-baseline assessment. Responder status was assessed relative to the short-term trial baseline (P05691). The CGI-BP-I (Overall Bipolar Illness) is a score on a 7-point scale for assessing the change from preceding phase of overall symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I overall score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, 84, 112, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: Percentage of participants
    number (not applicable)
        Day 7 (n=56, 48, 50)
    89.3
    89.6
    88
        Day 14 (n=53, 44, 43)
    86.8
    81.8
    88.4
        Day 28 (n=47, 36, 37)
    89.4
    88.9
    83.8
        Day 56 (n=42, 36, 35)
    95.2
    94.4
    85.7
        Day 84 (n=38, 33, 33)
    94.7
    90.9
    87.9
        Day 112 (n=36, 25, 28)
    91.7
    92
    92.9
        Day 182 (n=32, 27, 23)
    90.6
    92.6
    87
        Study Endpoint (n=57, 50, 50)
    89.5
    84
    80
    No statistical analyses for this end point

    Secondary: Change from Trial P05691 Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Days 7, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 Change from Trial P05691 Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Days 7, 182, and Study Endpoint
    End point description
    The MADRS measures depression and consists of 10 items, each rated on a scale from 0 to 6. The MADRS Total Score sums the scores from the 10 items, ranging from 0 to 60, with a higher numeric rating implying a greater degree of symptom severity. The reported measure is the change from short-term trial baseline (P05691) at each specified visit, analysed using an ANCOVA model including fixed effects for treatment and investigative site (or pooled site) and baseline value as a covariate; improvement in symptoms is represented by negative values. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 7, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    least squares mean (standard error)
        Day 7 (n=56, 48, 50)
    -7 ( 0.84 )
    -6 ( 0.9 )
    -6.6 ( 0.9 )
        Day 182 (n=32, 27, 23)
    -7.5 ( 1.28 )
    -7.7 ( 1.43 )
    -7.8 ( 1.46 )
        Study Endpoint (n=57, 50, 50)
    -6.9 ( 1.11 )
    -5.6 ( 1.17 )
    -5.9 ( 1.2 )
    No statistical analyses for this end point

    Secondary: Positive And Negative Syndrome Scale (PANSS) Total Score at Days 7, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 Positive And Negative Syndrome Scale (PANSS) Total Score at Days 7, 182, and Study Endpoint
    End point description
    The PANSS Total Score measures symptoms of schizophrenia and consists of responses to 30 items: 7 items from the positive subscale (P1-P7), 7 items from the negative subscale (N1-N7) and 16 items from the general psychopathology subscale (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Total Score sums the scores from all 30 items, and ranges from 30 to 210, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    arithmetic mean (standard deviation)
        Day 7 (n=56, 48, 50)
    49.1 ( 10.82 )
    48.2 ( 11.39 )
    46 ( 11.07 )
        Day 182 (n=32, 27, 23)
    45.6 ( 10.39 )
    44.6 ( 12.41 )
    42.4 ( 10.21 )
        Study Endpoint (n=57, 50, 50)
    48.3 ( 10.93 )
    47 ( 11.95 )
    47.5 ( 12.97 )
    No statistical analyses for this end point

    Secondary: PANSS Negative Subscale Score at Days 7, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 PANSS Negative Subscale Score at Days 7, 182, and Study Endpoint
    End point description
    The PANSS Negative subscale measures symptoms of schizophrenia and consists of responses to 7 items (N1-N7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Negative subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    arithmetic mean (standard deviation)
        Day 7 (n=56, 48, 50)
    11.4 ( 4.1 )
    11.7 ( 3.62 )
    10.7 ( 3.19 )
        Day 182 (n=32, 27, 23)
    11.6 ( 4.21 )
    11.7 ( 3.87 )
    10.3 ( 2.85 )
        Study Endpoint (n=57, 50, 50)
    11.9 ( 4.55 )
    11.8 ( 3.56 )
    11.2 ( 3.53 )
    No statistical analyses for this end point

    Secondary: PANSS Positive Subscale Score at Days 7, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 PANSS Positive Subscale Score at Days 7, 182, and Study Endpoint
    End point description
    The PANSS Positive subscale measures symptoms of schizophrenia and consists of responses to 7 items (P1-P7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Positive subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    arithmetic mean (standard deviation)
        Day 7 (n=56, 48, 50)
    12.1 ( 3.3 )
    11.3 ( 3.32 )
    11.3 ( 3.69 )
        Day 182 (n=32, 27, 23)
    10.2 ( 2.94 )
    10 ( 3.45 )
    10 ( 2.72 )
        Study Endpoint (n=57, 50, 50)
    11.1 ( 3.1 )
    10.6 ( 3.45 )
    11 ( 3.59 )
    No statistical analyses for this end point

    Secondary: PANSS General Psychopathology Subscale Score at Days 7, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 PANSS General Psychopathology Subscale Score at Days 7, 182, and Study Endpoint
    End point description
    The PANSS General Psychopathology subscale measures symptoms of schizophrenia and consists of responses to 16 items (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS General Psychopathology subscale sums the scores from all 16 items and ranges from 16 to 112, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    arithmetic mean (standard deviation)
        Day 7 (n=56, 48, 50)
    25.6 ( 5.54 )
    25.2 ( 6.07 )
    24 ( 5.98 )
        Day 182 (n=32, 27, 23)
    23.8 ( 5.54 )
    22.9 ( 7.26 )
    22 ( 5.81 )
        Study Endpoint (n=57, 50, 50)
    25.3 ( 5.69 )
    24.6 ( 7.13 )
    25.3 ( 7.75 )
    No statistical analyses for this end point

    Secondary: PANSS Marder Factor Positive Symptom Score at Days 7, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 PANSS Marder Factor Positive Symptom Score at Days 7, 182, and Study Endpoint
    End point description
    The PANSS Marder Factor Positive symptom score measures symptoms of schizophrenia and consists of responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Positive symptom score sums the scores from all 8 items and ranges from 8 to 56, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    arithmetic mean (standard deviation)
        Day 7 (n=56, 48, 50)
    13.5 ( 3.88 )
    12.7 ( 3.74 )
    11.8 ( 3.25 )
        Day 182 (n=32, 27, 23)
    11.4 ( 3.22 )
    11.4 ( 4.38 )
    10.7 ( 2.36 )
        Study Endpoint (n=57, 50, 50)
    12.3 ( 3.61 )
    11.9 ( 4.18 )
    11.7 ( 3.33 )
    No statistical analyses for this end point

    Secondary: PANSS Marder Factor Negative Symptom Score at Days 7, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 PANSS Marder Factor Negative Symptom Score at Days 7, 182, and Study Endpoint
    End point description
    The PANSS Marder Factor Negative symptom score measures symptoms of schizophrenia and consists of responses to 7 items (N1,N2,N3,N4,N6,G7,G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Negative symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    arithmetic mean (standard deviation)
        Day 7 (n=56, 48, 50)
    10.6 ( 4.15 )
    10.5 ( 3.36 )
    9.8 ( 3 )
        Day 182 (n=32, 27, 23)
    11.1 ( 4.29 )
    10.9 ( 3.3 )
    10 ( 2.87 )
        Study Endpoint (n=57, 50, 50)
    11.4 ( 4.83 )
    10.9 ( 3.67 )
    10.7 ( 3.62 )
    No statistical analyses for this end point

    Secondary: PANSS Marder Factor Disorganized Thought Symptom Score at Days 7, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 PANSS Marder Factor Disorganized Thought Symptom Score at Days 7, 182, and Study Endpoint
    End point description
    The PANSS Marder Factor Disorganized Thought symptom score measures symptoms of schizophrenia and consists of responses to 7 items (P2,N5,G5,G10,G11,G13,G15). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Disorganized Thought symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    arithmetic mean (standard deviation)
        Day 7 (n=56, 48, 50)
    11.3 ( 3.01 )
    11.4 ( 2.9 )
    11.4 ( 3.13 )
        Day 182 (n=32, 27, 23)
    10.3 ( 2.89 )
    10.8 ( 3.59 )
    10.3 ( 3.33 )
        Study Endpoint (n=57, 50, 50)
    10.9 ( 2.91 )
    11 ( 3.37 )
    11.1 ( 3.46 )
    No statistical analyses for this end point

    Secondary: PANSS Marder Factor Hostility/Excitement Symptom Score at Days 7, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 PANSS Marder Factor Hostility/Excitement Symptom Score at Days 7, 182, and Study Endpoint
    End point description
    The PANSS Marder Factor Hostility/Excitement symptom score measures symptoms of schizophrenia and consists of responses to 4 items (P4,P7,G8,G14). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Hostility/Excitement symptom score sums the score from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    arithmetic mean (standard deviation)
        Day 7 (n=56, 48, 50)
    7 ( 2.41 )
    6.7 ( 2.51 )
    7 ( 2.98 )
        Day 182 (n=32, 27, 23)
    5.9 ( 1.83 )
    5.5 ( 1.89 )
    5.4 ( 1.83 )
        Study Endpoint (n=57, 50, 50)
    6.6 ( 2.27 )
    6 ( 2.29 )
    6.9 ( 3.13 )
    No statistical analyses for this end point

    Secondary: PANSS Marder Factor Anxiety/Depression Symptom Score at Days 7, 182, and Study Endpoint

    		 Close Top of page
    End point title
    		 PANSS Marder Factor Anxiety/Depression Symptom Score at Days 7, 182, and Study Endpoint
    End point description
    The PANSS Marder Factor Anxiety/Depression symptom score measures symptoms of schizophrenia and consists of responses to 4 items (G2,G3,G4,G6). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Anxiety/Depression symptom score sums the scores from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. Population for this analysis was the FAS, defined as all randomized participants from PO5691 who received ≥1 dose of study drug in PO5692 and had ≥1 post-baseline Y-MRS Total Score assessment.
    End point type
    Secondary
    End point timeframe
    Days 7, 182, and Study Endpoint
    End point values
    		 Placebo / Asenapine 5 mg Asenapine 5 mg / Asenapine 5 mg Asenapine 10 mg / Asenapine 10 mg
    Number of subjects analysed
    59
    52
    50
    Units: units on a scale
    arithmetic mean (standard deviation)
        Day 7 (n=56, 48, 50)
    6.7 ( 2.57 )
    7 ( 3.13 )
    6 ( 2.99 )
        Day 182 (n=32, 27, 23)
    6.8 ( 2.69 )
    6 ( 2.92 )
    6 ( 2.66 )
        Study Endpoint (n=57, 50, 50)
    7.1 ( 2.75 )
    7.2 ( 3.55 )
    7.1 ( 3.64 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 30 days after last dose of study drug (up to approximately 30 weeks).
    Adverse event reporting additional description
    Analysis population was the ATS which included all randomized participants from the short-term trial (PO5691) who received ≥1 dose of study drug in the current extension trial (PO5692).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Placebo / Asenapine 5 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered placebo for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks.

    Reporting group title
    Asenapine 5 mg Overall
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered either placebo or one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were administered one 5 mg asenapine tablet BID for 26 weeks. The 'asenapine 5 mg overall' arm represents the 'placebo / asenapine 5 mg' and 'asenapine 5 mg / asenapine 5 mg' arms combined.

    Reporting group title
    Asenapine 10 mg / Asenapine 10 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered one 10 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 10 mg asenapine tablet BID) for 26 weeks.

    Reporting group title
    Asenapine 5 mg / Asenapine 5 mg
    Reporting group description
    		 In the previous short-term trial PO5691, participants were administered one 5 mg asenapine tablet BID for 21 days; in the current extension trial (PO5692), participants were assigned to the same treatment regimen (ie, one 5 mg asenapine tablet BID) for 26 weeks.

    Serious adverse events
    		 Placebo / Asenapine 5 mg Asenapine 5 mg Overall Asenapine 10 mg / Asenapine 10 mg Asenapine 5 mg / Asenapine 5 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 60 (5.00%)
    3 / 113 (2.65%)
    2 / 51 (3.92%)
    0 / 53 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Cardiac disorders
    Angina Pectoris
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 113 (0.00%)
    1 / 51 (1.96%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 113 (0.88%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Bipolar I Disorder
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 113 (0.88%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Major Depression
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 113 (0.88%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mania
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 113 (0.00%)
    1 / 51 (1.96%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo / Asenapine 5 mg Asenapine 5 mg Overall Asenapine 10 mg / Asenapine 10 mg Asenapine 5 mg / Asenapine 5 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    34 / 60 (56.67%)
    59 / 113 (52.21%)
    33 / 51 (64.71%)
    25 / 53 (47.17%)
    Injury, poisoning and procedural complications
    Accidental Overdose
         subjects affected / exposed
    4 / 60 (6.67%)
    6 / 113 (5.31%)
    2 / 51 (3.92%)
    2 / 53 (3.77%)
         occurrences all number
    8
    10
    3
    2
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 60 (1.67%)
    4 / 113 (3.54%)
    1 / 51 (1.96%)
    3 / 53 (5.66%)
         occurrences all number
    1
    4
    1
    3
    Nervous system disorders
    Akathisia
         subjects affected / exposed
    5 / 60 (8.33%)
    7 / 113 (6.19%)
    10 / 51 (19.61%)
    2 / 53 (3.77%)
         occurrences all number
    7
    9
    10
    2
    Dysgeusia
         subjects affected / exposed
    1 / 60 (1.67%)
    3 / 113 (2.65%)
    3 / 51 (5.88%)
    2 / 53 (3.77%)
         occurrences all number
    1
    3
    3
    2
    Headache
         subjects affected / exposed
    5 / 60 (8.33%)
    7 / 113 (6.19%)
    5 / 51 (9.80%)
    2 / 53 (3.77%)
         occurrences all number
    8
    11
    5
    3
    Sedation
         subjects affected / exposed
    6 / 60 (10.00%)
    10 / 113 (8.85%)
    6 / 51 (11.76%)
    4 / 53 (7.55%)
         occurrences all number
    6
    10
    6
    4
    Somnolence
         subjects affected / exposed
    7 / 60 (11.67%)
    12 / 113 (10.62%)
    6 / 51 (11.76%)
    5 / 53 (9.43%)
         occurrences all number
    7
    12
    6
    5
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 113 (0.88%)
    3 / 51 (5.88%)
    1 / 53 (1.89%)
         occurrences all number
    0
    1
    4
    1
    Dry Mouth
         subjects affected / exposed
    7 / 60 (11.67%)
    10 / 113 (8.85%)
    2 / 51 (3.92%)
    3 / 53 (5.66%)
         occurrences all number
    7
    10
    2
    3
    Hypoaesthesia Oral
         subjects affected / exposed
    6 / 60 (10.00%)
    9 / 113 (7.96%)
    10 / 51 (19.61%)
    3 / 53 (5.66%)
         occurrences all number
    6
    9
    11
    3
    Toothache
         subjects affected / exposed
    1 / 60 (1.67%)
    4 / 113 (3.54%)
    0 / 51 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    1
    5
    0
    4
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 60 (0.00%)
    4 / 113 (3.54%)
    3 / 51 (5.88%)
    4 / 53 (7.55%)
         occurrences all number
    0
    5
    5
    5
    Insomnia
         subjects affected / exposed
    6 / 60 (10.00%)
    9 / 113 (7.96%)
    4 / 51 (7.84%)
    3 / 53 (5.66%)
         occurrences all number
    6
    9
    4
    3
    Infections and infestations
    Upper Respiratory Tract Infection
         subjects affected / exposed
    7 / 60 (11.67%)
    10 / 113 (8.85%)
    2 / 51 (3.92%)
    3 / 53 (5.66%)
         occurrences all number
    7
    10
    2
    3
    Metabolism and nutrition disorders
    Increased Appetite
         subjects affected / exposed
    5 / 60 (8.33%)
    6 / 113 (5.31%)
    2 / 51 (3.92%)
    1 / 53 (1.89%)
         occurrences all number
    5
    6
    2
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Aug 2011
    • Text regarding drug-induced liver injury (as a closely monitored event [CME]) was revised based on latest guidance of the Food and Drug Administration (FDA). • A new CME of 'suicidal ideation and/or behaviour' was added. • The SAE section was updated to include 'cancer' as SAE outcome #6. • The urinalysis tests listed as procedures for safety assessments was revised. • “Incidents associated with the device” was deleted from the list of events requiring expedited reporting of safety observations by the investigator to the sponsor since this was not relevant to the trial. • Sections in the protocol relating to medication error, potential medication error, and incident were deleted.
    10 Oct 2011
    • A new CME of 'drug hypersensitivity reactions' was added. • Text relating to the monitoring of liver enzymes was updated to be consistent with FDA Drug Induced Liver Injury guidance. • “Antiemetics containing dopamine agonists” was corrected to “Antiemetics containing dopamine antagonists” in Table 2 of the protocol which described medications, supplements and other substances and treatments prohibited during treatment with trial medication.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 20 05:39:08 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA