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    Clinical Trial Results:
    A Long-term, Phase 3, Multicenter, Open-label Trial to Evaluate the Safety and Tolerability of Oral OPC-34712 as Maintenance Treatment in Adults with Schizophrenia

    Summary
    EudraCT number
    2011-002514-37
    Trial protocol
    LV   PL   SK  
    Global end of trial date
    25 Feb 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    26 Feb 2017
    First version publication date
    26 Feb 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    331-10-237
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01397786
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Otsuka Pharmaceutical Development & Commercialization, Inc.
    Sponsor organisation address
    2440 Research Boulevard, Rockville, Maryland, United States, 20850
    Public contact
    Otsuka Data Transparency Department, Otsuka Pharmaceutical Development & Commercialization, Inc., DT-inquiry@otsuka.jp
    Scientific contact
    Otsuka Data Transparency Department, Otsuka Pharmaceutical Development & Commercialization, Inc., DT-inquiry@otsuka.jp
    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
    25 Feb 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    25 Feb 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Feb 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the long-term safety and tolerability of oral brexpiprazole as monotherapy in adults with schizophrenia. This trial was conducted on an outpatient basis.
    Protection of trial subjects
    In accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline and the applicable local laws and regulatory requirements of the countries in which the trial was conducted, copies of the protocol, amendments, and informed consent form (ICF) were reviewed and approved by the governing institutional review board (IRB) or independent ethics committee (IEC) for each investigational site or country, as appropriate, prior to trial start or prior to implementation of the amendment at that site or country. Written informed consent was obtained from all participants. Informed consent was obtained and documented prior to initiation of any procedures that were performed solely for the purpose of determining eligibility for this trial, including withdrawal from current medication(s). All participants received copies of their signed and dated ICFs.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    15 Sep 2011
    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
    Taiwan: 7
    Country: Number of subjects enrolled
    Turkey: 12
    Country: Number of subjects enrolled
    Ukraine: 147
    Country: Number of subjects enrolled
    United States: 432
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Colombia: 57
    Country: Number of subjects enrolled
    Croatia: 17
    Country: Number of subjects enrolled
    Japan: 4
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 9
    Country: Number of subjects enrolled
    Latvia: 5
    Country: Number of subjects enrolled
    Malaysia: 31
    Country: Number of subjects enrolled
    Mexico: 34
    Country: Number of subjects enrolled
    Philippines: 6
    Country: Number of subjects enrolled
    Poland: 4
    Country: Number of subjects enrolled
    Puerto Rico: 14
    Country: Number of subjects enrolled
    Romania: 80
    Country: Number of subjects enrolled
    Russian Federation: 121
    Country: Number of subjects enrolled
    Serbia: 89
    Worldwide total number of subjects
    1072
    EEA total number of subjects
    106
    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)
    1072
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    This trial was conducted in a total of 1072 participants (1044 of whom entered the open-label treatment phase) at 202 trial sites.

    Pre-assignment
    Screening details
    Enrollment was drawn from eligible participants who could potentially benefit from monotherapy treatment with oral brexpiprazole for schizophrenia and included rollover participants from the double-blind, phase-3 efficacy trials (ie, Trials 2011-002513-11, 2011-002538-38, and 2011-005766-38) and de novo participants from select sites.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded
    Blinding implementation details
    This was an open-label trial.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Prior Brexpiprazole
    Arm description
    Participants who rolled over from, and received blinded brexpiprazole in, one of the randomized, double-blind, placebo-controlled Phase 3 efficacy studies (Trials 2011-002513-11; 2011-002538-38; 2011-005766-38); all received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.
    Arm type
    Active comparator

    Investigational medicinal product name
    Prior Brexpiprazole
    Investigational medicinal product code
    Other name
    OPC-34712
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received oral brexpiprazole 1 to 4mg/day for 4 weeks.

    Arm title
    Prior Placebo
    Arm description
    Participants who rolled over from, and received blinded placebo in, one of the randomized, double-blind, placebo-controlled Phase 3 efficacy studies (Trials 2011-002513-11; 2011-002538-38; 2011-005766-38); all received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.
    Arm type
    Active comparator

    Investigational medicinal product name
    Prior Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received oral placebo for 4 weeks.

    Arm title
    De Novo
    Arm description
    Participants who had not previously participated in a brexpiprazole clinical study and who received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.
    Arm type
    Experimental

    Investigational medicinal product name
    De Novo
    Investigational medicinal product code
    Other name
    Brexpiprazole; OPC-34712
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    De Novo participants received brexpiprazole 1-4 mg/day for 4 weeks.

    Number of subjects in period 1
    Prior Brexpiprazole Prior Placebo De Novo
    Started
    611
    204
    257
    Completed
    308
    109
    91
    Not completed
    303
    95
    166
         Protocol deviation
    1
    2
    4
         Physician decision
    9
    1
    4
         Met withdrawal criteria
    38
    5
    45
         Lack of efficacy
    22
    7
    15
         Adverse events
    109
    23
    35
         Consent withdrawn by subject
    102
    45
    35
         Lost to follow-up
    22
    12
    28

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Prior Brexpiprazole
    Reporting group description
    Participants who rolled over from, and received blinded brexpiprazole in, one of the randomized, double-blind, placebo-controlled Phase 3 efficacy studies (Trials 2011-002513-11; 2011-002538-38; 2011-005766-38); all received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.

    Reporting group title
    Prior Placebo
    Reporting group description
    Participants who rolled over from, and received blinded placebo in, one of the randomized, double-blind, placebo-controlled Phase 3 efficacy studies (Trials 2011-002513-11; 2011-002538-38; 2011-005766-38); all received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.

    Reporting group title
    De Novo
    Reporting group description
    Participants who had not previously participated in a brexpiprazole clinical study and who received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.

    Reporting group values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects
    611 204 257 1072
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    611 204 257 1072
        From 65-84 years
    0 0 0 0
        85 years and over
    0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    38.5 ± 10.8 39.6 ± 10.8 44.1 ± 11.1 -
    Gender categorical
    Units: Subjects
        Female
    245 79 85 409
        Male
    366 125 172 663

    End points

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    End points reporting groups
    Reporting group title
    Prior Brexpiprazole
    Reporting group description
    Participants who rolled over from, and received blinded brexpiprazole in, one of the randomized, double-blind, placebo-controlled Phase 3 efficacy studies (Trials 2011-002513-11; 2011-002538-38; 2011-005766-38); all received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.

    Reporting group title
    Prior Placebo
    Reporting group description
    Participants who rolled over from, and received blinded placebo in, one of the randomized, double-blind, placebo-controlled Phase 3 efficacy studies (Trials 2011-002513-11; 2011-002538-38; 2011-005766-38); all received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.

    Reporting group title
    De Novo
    Reporting group description
    Participants who had not previously participated in a brexpiprazole clinical study and who received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.

    Subject analysis set title
    Total
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants who rolled over from, and received blinded brexpiprazole/placebo in, one of the randomized, double blind, placebo controlled Phase 3 efficacy studies (Trials 2011-002513-11, 2011-002538-38, and 2011-005766-38); or de novo patients. All received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.

    Primary: Percentage of Participants With Adverse Events (AEs)

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    End point title
    Percentage of Participants With Adverse Events (AEs) [1]
    End point description
    A treatment-emergent adverse event (TEAE) is defined as an AE that started after start of investigational medicinal product (IMP) treatment; or if the event was continuous from baseline and was serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of IMP. Safety sample included those participants who had at least one post-baseline efficacy evaluation for Positive and Negative Syndrome Scale (PANSS) total score.
    End point type
    Primary
    End point timeframe
    From Baseline up to 52 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 inferential statistical analysis was performed.
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    605
    202
    224
    1031
    Units: percentage of participants
    number (not applicable)
        With AEs
    60.2
    56.4
    65.2
    60.5
        With TEAEs
    60
    56.4
    65.2
    60.4
        With SAEs
    14.9
    8.9
    11.2
    12.9
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score

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    End point title
    Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score
    End point description
    The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    223
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 375, 134, 123, 632)
    -6.9 ± 12.9
    -12.5 ± 14.9
    -6.6 ± 13.6
    -8 ± 13.6
        Mean change at Week 52 (n= 226, 93, 91, 410)
    -11 ± 14.4
    -18.4 ± 16.9
    -8.8 ± 12.6
    -12.2 ± 15
        Mean change at Last Visit (n= 591, 198, 223, 1012)
    -3.8 ± 16.7
    -9.7 ± 18.7
    -3.5 ± 14.3
    -4.9 ± 16.8
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in PANSS Positive Subscale Score

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    End point title
    Mean Change From Baseline in PANSS Positive Subscale Score
    End point description
    The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    123
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 375, 134, 123, 632)
    -2.1 ± 4.5
    -4.1 ± 5.4
    -1.7 ± 4.3
    -2.4 ± 4.7
        Mean change at Week 52 (n= 226, 93, 91, 410)
    -3.2 ± 4.6
    -5.8 ± 5.2
    -2.3 ± 4.1
    -3.6 ± 4.8
        Mean change at Last Visit(n= 591, 198, 223, 1012)
    -0.9 ± 5.9
    -2.8 ± 6.4
    -1 ± 4.9
    -1.3 ± 5.8
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in PANSS Negative Subscale Score

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    End point title
    Mean Change From Baseline in PANSS Negative Subscale Score
    End point description
    The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In negative subscale the severity was rated for the following 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    223
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 375, 134, 123, 632)
    -1.4 ± 3.7
    -2.4 ± 4.3
    -1.3 ± 3.8
    -1.6 ± 3.9
        Mean change at Week 52 (n= 226, 93, 91, 410)
    -2.7 ± 4.5
    -3.7 ± 5.4
    -2 ± 3.7
    -2.8 ± 4.6
        Mean change at Last Visit (n= 591, 198, 223, 1012)
    -1 ± 4.1
    -2.4 ± 5
    -0.6 ± 4.2
    -1.2 ± 4.3
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score

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    End point title
    Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score
    End point description
    The severity of illness for each participant were rated using the CGI-S. To perform this assessment, the investigator were to answer the following question: "Considering your total clinical experience with this particular population, how mentally ill was the participant at that time?" Response choices include: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    223
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 375, 134, 123, 632)
    -0.35 ± 0.79
    -0.6 ± 0.98
    -0.24 ± 0.88
    -0.38 ± 0.86
        Mean change at Week 52 (n= 226, 93, 91, 410)
    -0.55 ± 0.86
    -0.97 ± 0.98
    -0.48 ± 0.86
    -0.63 ± 0.91
        Mean change at Last Visit (n= 591, 198, 223, 1012)
    -0.14 ± 1.04
    -0.46 ± 1.12
    -0.17 ± 0.88
    -0.21 ± 1.03
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in Personal and Social Performance (PSP) Scale Total Score

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    End point title
    Mean Change From Baseline in Personal and Social Performance (PSP) Scale Total Score
    End point description
    The PSP was a validated clinician-rated scale that measured personal and social functioning in four domains: socially useful activities (e.g, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment in each of these domains was rated as absent, mild, manifest, marked, severe, or very severe. These ratings were then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment that determined the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented manifest disabilities of various degrees and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision. The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    123
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 366, 134, 123, 623)
    4.5 ± 9.7
    6.5 ± 11.3
    4.5 ± 9
    4.9 ± 10
        Mean change at Week 52 (n= 223, 93, 91, 407)
    7 ± 10.6
    9.6 ± 11.9
    7.6 ± 10.8
    7.7 ± 11
        Mean change at Last Visit (n= 569, 196, 219, 984)
    1.8 ± 12.4
    5.1 ± 12.8
    2.7 ± 11
    2.7 ± 12.2
    No statistical analyses for this end point

    Secondary: Mean Clinical Global Impression - Improvement Score

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    End point title
    Mean Clinical Global Impression - Improvement Score
    End point description
    The efficacy of study medication was rated for each participant using the CGI-I. The investigator rated the participants total improvement whether or not it was due to the drug treatment. All responses were compared to the participants condition at Screening/Baseline (i.e, Week 6 visit of Protocol NCT00905307). Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    598
    198
    123
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Week 26 (n= 381, 134, 123, 638)
    3 ± 1.13
    2.77 ± 0.99
    3 ± 1.13
    2.95 ± 1.1
        Week 52 (n= 226, 93, 91, 410)
    2.66 ± 1.13
    2.26 ± 0.97
    2.76 ± 1.09
    2.59 ± 1.1
        Last Visit (n= 598, 198, 223, 1019)
    3.31 ± 1.43
    2.96 ± 1.33
    3.3 ± 1.27
    3.24 ± 1.38
    No statistical analyses for this end point

    Secondary: Response Rate

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    End point title
    Response Rate
    End point description
    Response rate was defined as a reduction of ≥ 30% from Baseline in PANSS total score or CGI-I score of 1 (very much improved) or 2 (much improved) at the Last Visit. The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    605
    202
    224
    1031
    Units: Percentage of participants
        number (not applicable)
    34.2
    42.6
    27.2
    34.3
    No statistical analyses for this end point

    Secondary: Discontinuation Rate for Lack of Efficacy

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    End point title
    Discontinuation Rate for Lack of Efficacy
    End point description
    Discontinuation rate for the participants who discontinued due to lack of efficacy were examined. The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    605
    202
    224
    1031
    Units: percentage of participants
        number (not applicable)
    3.6
    3.5
    6.3
    4.2
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score

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    End point title
    Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score
    End point description
    The PEC score consisted of five PANSS items: excitement (P4), hostility (P7), tension (G4), uncooperativeness (G8), and poor impulse control (G14). Each of the items were rated on a scale of 1 (absent) to 7 (extreme). The PEC scores ranged from 5 (not present) to 35 (extremely severe). The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    123
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 375, 134, 123, 632)
    -0.6 ± 3.1
    -1.8 ± 3.7
    -0.7 ± 3.1
    -0.9 ± 3.3
        Mean change at Week 52 (n= 226, 93, 91, 410)
    -1.2 ± 3.2
    -2.6 ± 3.4
    -1 ± 2.9
    -1.5 ± 3.2
        Mean change at Last Visit (n= 591, 198, 223, 1012)
    0.1 ± 4.1
    -0.9 ± 4.2
    -0.3 ± 3.5
    -0.2 ± 4
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score

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    End point title
    Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score
    End point description
    Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome). The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    123
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 375, 134, 123, 632)
    -2.6 ± 4.8
    -4.7 ± 5.5
    -2 ± 5.2
    -2.9 ± 5.1
        Mean change at Week 52 (n= 226, 93, 91, 410)
    -3.9 ± 5.2
    -6.6 ± 5.7
    -2.6 ± 4.8
    -4.2 ± 5.4
        Mean change at Last Visit (n= 591, 198, 223, 1012)
    -1.6 ± 5.9
    -3.5 ± 6.5
    -1.3 ± 5
    -1.9 ± 5.9
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score

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    End point title
    Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score
    End point description
    Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome). The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    123
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 375, 134, 123, 632)
    -1.5 ± 3.6
    -2.2 ± 4
    -1.7 ± 4.1
    -1.7 ± 3.8
        Mean change at Week 52 (n= 226, 93, 91, 410)
    -2.6 ± 4.3
    -3.9 ± 5
    -2.2 ± 3.8
    -2.8 ± 4.4
        Mean change at Last Visit (n= 591, 198, 223, 1012)
    -1 ± 4.1
    -2.3 ± 5.1
    -0.7 ± 4.1
    -1.2 ± 4.4
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score

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    End point title
    Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score
    End point description
    Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome). The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    123
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 375, 134, 123, 632)
    -1.7 ± 3.3
    -2.6 ± 3.5
    -1.7 ± 3.5
    -1.9 ± 3.4
        Mean change at Week 52 (n= 226, 93, 91, 410)
    -2.9 ± 3.7
    -3.7 ± 4.6
    -2.3 ± 3.7
    -2.9 ± 4
        Mean change at Last Visit (n= 591, 198, 223, 1012)
    -1.2 ± 4.2
    -2.2 ± 4.5
    -0.9 ± 4
    -1.4 ± 4.2
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score

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    End point title
    Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score
    End point description
    Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome). The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    123
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 375, 134, 123, 632)
    -0.4 ± 2.7
    -1.4 ± 3.1
    -0.6 ± 2.6
    -0.6 ± 2.8
        Mean change at Week 52 (n= 226, 93, 91, 410)
    -0.8 ± 2.7
    -1.9 ± 2.9
    -0.9 ± 2.3
    -1.1 ± 2.7
        Mean change at Last Visit (n= 591, 198, 223, 1012)
    0.2 ± 3.4
    -0.7 ± 3.5
    -0.3 ± 3
    -0.1 ± 3.4
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score

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    End point title
    Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score
    End point description
    Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The anxiety/depression factor score is the sum of score from the 4 items on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome). The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
    End point type
    Secondary
    End point timeframe
    From Baseline up to 52 Weeks
    End point values
    Prior Brexpiprazole Prior Placebo De Novo Total
    Number of subjects analysed
    591
    198
    123
    1012
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Mean change at Week 26 (n= 375, 134, 123, 632)
    -0.7 ± 2.6
    -1.5 ± 3
    -0.7 ± 3.4
    -0.9 ± 2.9
        Mean change at Week 52 (n= 226, 93, 91, 410)
    -0.9 ± 2.5
    -2.4 ± 2.9
    -0.8 ± 3.5
    -1.2 ± 2.9
        Mean change at Last Visit (n= 591, 198, 223, 1012)
    -0.2 ± 3.2
    -0.9 ± 3.4
    -0.4 ± 3.8
    -0.4 ± 3.4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The trial required that participants be actively monitored for AEs up to 30 (+2) days after the last dose of study drug.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    De Novo (Phase A)
    Reporting group description
    Participants underwent cross-titration to oral brexpiprazole for 4 weeks in Phase A. DeNovo participants in Phase A received brexpiprazole monotherapy starting dose of 2 mg daily at the conversion Week 4 visit (baseline visit of Phase B).

    Reporting group title
    Prior Brexpiprazole (Phase B)
    Reporting group description
    Participants who rolled over from, and received blinded brexpiprazole in, one of the randomized, double-blind, placebo-controlled Phase 3 efficacy studies (Trials 2011-002513-11; 2011-002538-38; 2011-005766-38); all received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.

    Reporting group title
    Prior Placebo (Phase B)
    Reporting group description
    Participants who rolled over from, and received blinded placebo in, one of the randomized, double-blind, placebo-controlled Phase 3 efficacy studies (Trials 2011-002513-11; 2011-002538-38; 2011-005766-38); all received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.

    Reporting group title
    De Novo (Phase B)
    Reporting group description
    Participants who had not previously participated in a brexpiprazole clinical study and who received 1-4 mg of daily treatment with open label brexpiprazole in trial 2011-002514-37.

    Serious adverse events
    De Novo (Phase A) Prior Brexpiprazole (Phase B) Prior Placebo (Phase B) De Novo (Phase B)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 226 (1.77%)
    90 / 605 (14.88%)
    18 / 202 (8.91%)
    25 / 256 (9.77%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Pneumonia
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    0 / 202 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    0 / 202 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Endometrial cancer
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine cancer
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    1 / 202 (0.50%)
    0 / 256 (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
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    0 / 202 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    0 / 202 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    0 / 202 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Akathisia
         subjects affected / exposed
    0 / 226 (0.00%)
    2 / 605 (0.33%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Acute psychosis
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Agitation
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    0 / 202 (0.00%)
    2 / 256 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    1 / 202 (0.50%)
    0 / 256 (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
    Emotional disorder
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    1 / 202 (0.50%)
    0 / 256 (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
    Hallucination, auditory
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 226 (0.44%)
    7 / 605 (1.16%)
    3 / 202 (1.49%)
    4 / 256 (1.56%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 7
    0 / 3
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Schizophrenia
         subjects affected / exposed
    2 / 226 (0.88%)
    68 / 605 (11.24%)
    12 / 202 (5.94%)
    10 / 256 (3.91%)
         occurrences causally related to treatment / all
    0 / 2
    26 / 71
    5 / 14
    6 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Schizophrenia paranoid type
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    1 / 202 (0.50%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal behaviour
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 605 (0.00%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    0 / 202 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer perforation
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    0 / 202 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 226 (0.00%)
    2 / 605 (0.33%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 226 (0.00%)
    2 / 605 (0.33%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 605 (0.17%)
    0 / 202 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 226 (0.00%)
    0 / 605 (0.00%)
    0 / 202 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    De Novo (Phase A) Prior Brexpiprazole (Phase B) Prior Placebo (Phase B) De Novo (Phase B)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 226 (0.00%)
    166 / 605 (27.44%)
    53 / 202 (26.24%)
    95 / 256 (37.11%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 226 (0.00%)
    10 / 605 (1.65%)
    2 / 202 (0.99%)
    20 / 256 (7.81%)
         occurrences all number
    0
    10
    3
    20
    Investigations
    Weight increased
         subjects affected / exposed
    0 / 226 (0.00%)
    47 / 605 (7.77%)
    15 / 202 (7.43%)
    23 / 256 (8.98%)
         occurrences all number
    0
    53
    16
    25
    Nervous system disorders
    Akathisia
         subjects affected / exposed
    0 / 226 (0.00%)
    22 / 605 (3.64%)
    14 / 202 (6.93%)
    14 / 256 (5.47%)
         occurrences all number
    0
    25
    21
    14
    Headache
         subjects affected / exposed
    0 / 226 (0.00%)
    42 / 605 (6.94%)
    14 / 202 (6.93%)
    24 / 256 (9.38%)
         occurrences all number
    0
    51
    16
    29
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 226 (0.00%)
    30 / 605 (4.96%)
    7 / 202 (3.47%)
    23 / 256 (8.98%)
         occurrences all number
    0
    42
    15
    31
    Insomnia
         subjects affected / exposed
    0 / 226 (0.00%)
    51 / 605 (8.43%)
    17 / 202 (8.42%)
    32 / 256 (12.50%)
         occurrences all number
    0
    71
    25
    38

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Jun 2012
    Inclusion of rollover participants from Trial 2011-005766-38.
    19 Jun 2014
    Reduction of trial duration from 52 to 26 weeks.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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