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 Phase 3, 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of 2 Fixed Doses of Brexpiprazole (OPC-34712) in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer’s Type

    Summary
    EudraCT number
    		 2013-000504-41
    Trial protocol
    		 DE   ES   HR  
    Global end of trial date
    15 Mar 2017

    Results information
    Results version number
    		 v2(current)
    This version publication date
    24 Dec 2020
    First version publication date
    14 Jun 2018
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    331-12-283
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01862640
    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
    Global Clinical Development, Otsuka Pharmaceutical Development & Commercialization, Inc., 1-609 524-6788, clinicaltransparency@otsuka-us.com
    Scientific contact
    Global Clinical Development, Otsuka Pharmaceutical Development & Commercialization, Inc., 1-609 524-6788, clinicaltransparency@otsuka-us.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
    15 Mar 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Mar 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Mar 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy of 2 fixed doses (1 mg/day and 2 mg/day) of brexpiprazole with placebo in participants with agitation associated with Alzheimer’s dementia, as assessed by the Cohen-Mansfield Agitation Inventory (CMAI) after 12 weeks of treatment.
    Protection of trial subjects
    This study was conducted in accordance with International Council on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Jul 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Croatia: 37
    Country: Number of subjects enrolled
    Germany: 13
    Country: Number of subjects enrolled
    Russian Federation: 126
    Country: Number of subjects enrolled
    Serbia: 53
    Country: Number of subjects enrolled
    Spain: 19
    Country: Number of subjects enrolled
    Ukraine: 64
    Country: Number of subjects enrolled
    United States: 121
    Worldwide total number of subjects
    433
    EEA total number of subjects
    69
    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)
    72
    From 65 to 84 years
    321
    85 years and over
    40

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants who met all the inclusion and none of the exclusion criteria were enrolled in this study. The study was conducted in 433 participants at 81 sites in 7 countries: Croatia, Germany, Serbia, Spain, Russia, Ukraine, and the United States.

    Pre-assignment
    Screening details
    		 Participants attended a screening period ranging from 2 to 42 days. The purpose of the screening period was to determine the participant's eligibility and to washout prohibited concomitant pharmacotherapy prior to randomization.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Brexpiprazole 0.5 mg/day
    Arm description
    		 All randomized participants received orally brexpiprazole 0.25 milligrams (mg)/day as a starting dose, which was up titrated to 0.5 mg/day. The investigational medicinal product (IMP) was administered once daily in the form of a tablet.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Brexpiprazole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All randomized participants received orally a brexpiprazole 0.5 mg/day tablet.

    Arm title
    		 Brexpiprazole 1 mg/day
    Arm description
    		 All randomized participants received orally brexpiprazole 0.25 mg/day as a starting dose, which was up titrated to 1 mg/day. The IMP was administered once daily in the form of a tablet.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Brexpiprazole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All randomized participants received orally a brexpiprazole 1.0 mg/day tablet.

    Arm title
    		 Brexpiprazole 2 mg/day
    Arm description
    		 All randomized participants received orally brexpiprazole 0.25 mg/day as a starting dose, which was up titrated to 2 mg/day. The IMP was administered once daily in the form of a tablet.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Brexpiprazole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All randomized participants received orally a brexpiprazole 2.0 mg/day tablet.

    Arm title
    		 Placebo
    Arm description
    		 All randomized participants received orally brexpiprazole-matching Placebo. The Placebo was administered once daily in the form of a tablet.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All randomized participants received orally a brexpiprazole-matching placebo tablet.

    Number of subjects in period 1
    		Brexpiprazole 0.5 mg/day Brexpiprazole 1 mg/day Brexpiprazole 2 mg/day Placebo
    Started
    20
    137
    140
    136
    Completed
    13
    121
    122
    121
    Not completed
    7
    16
    18
    15
         Consent withdrawn by subject
    2
    4
    8
    5
         Participant Withdrawn By Investigator
    -
    1
    1
    1
         Adverse event, non-fatal
    4
    10
    6
    8
         Protocol Deviation
    -
    -
    1
    -
         Participant Met Withdrawal Criteria
    1
    1
    2
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Brexpiprazole 0.5 mg/day
    Reporting group description
    		 All randomized participants received orally brexpiprazole 0.25 milligrams (mg)/day as a starting dose, which was up titrated to 0.5 mg/day. The investigational medicinal product (IMP) was administered once daily in the form of a tablet.

    Reporting group title
    Brexpiprazole 1 mg/day
    Reporting group description
    		 All randomized participants received orally brexpiprazole 0.25 mg/day as a starting dose, which was up titrated to 1 mg/day. The IMP was administered once daily in the form of a tablet.

    Reporting group title
    Brexpiprazole 2 mg/day
    Reporting group description
    		 All randomized participants received orally brexpiprazole 0.25 mg/day as a starting dose, which was up titrated to 2 mg/day. The IMP was administered once daily in the form of a tablet.

    Reporting group title
    Placebo
    Reporting group description
    		 All randomized participants received orally brexpiprazole-matching Placebo. The Placebo was administered once daily in the form of a tablet.

    Reporting group values
    		 Brexpiprazole 0.5 mg/day Brexpiprazole 1 mg/day Brexpiprazole 2 mg/day Placebo Total
    Number of subjects
    		 20 137 140 136 433
    Age categorical
    Units:
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 73.9 ( 9.1 ) 73.8 ( 8.8 ) 73.7 ( 8.1 ) 74.1 ( 8.0 ) -
    Gender categorical
    Units: Subjects
        Female
    		 12 78 79 70 239
        Male
    		 8 59 61 66 194
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 0 1 2 1 4
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 0 2 5 5 12
        White
    		 20 134 133 130 417
        More than one race
    		 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0 0

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Brexpiprazole 0.5 mg/day
    Reporting group description
    		 All randomized participants received orally brexpiprazole 0.25 milligrams (mg)/day as a starting dose, which was up titrated to 0.5 mg/day. The investigational medicinal product (IMP) was administered once daily in the form of a tablet.

    Reporting group title
    Brexpiprazole 1 mg/day
    Reporting group description
    		 All randomized participants received orally brexpiprazole 0.25 mg/day as a starting dose, which was up titrated to 1 mg/day. The IMP was administered once daily in the form of a tablet.

    Reporting group title
    Brexpiprazole 2 mg/day
    Reporting group description
    		 All randomized participants received orally brexpiprazole 0.25 mg/day as a starting dose, which was up titrated to 2 mg/day. The IMP was administered once daily in the form of a tablet.

    Reporting group title
    Placebo
    Reporting group description
    		 All randomized participants received orally brexpiprazole-matching Placebo. The Placebo was administered once daily in the form of a tablet.

    Primary: Change From Baseline In The Cohen-Mansfield Agitation Inventory (CMAI) Total Score After 12 Weeks Of Brexpiprazole Treatment

    		 Close Top of page
    End point title
    		 Change From Baseline In The Cohen-Mansfield Agitation Inventory (CMAI) Total Score After 12 Weeks Of Brexpiprazole Treatment [1]
    End point description
    To compare the efficacy of 2 fixed doses (1 mg/day and 2 mg/day) of brexpiprazole with placebo in participants with agitation associated with dementia of the Alzheimer's type, by the assessment of CMAI after 12 weeks of treatment. The CMAI assesses the frequency of agitated behaviors in elderly persons, such as hitting, cursing, and restlessness. It consists of 29 items all rated on a 1 to 7 scale with 1 being the “best” rating and 7 being the “worst” rating. The minimum possible CMAI total score is 29, and the maximum possible CMAI total score is 203. A decrease in score indicates improvement in symptoms. To control the overall type I error at 0.05 level when making 2 comparisons of brexpiprazole doses versus placebo, statistical testing was carried out using a hierarchical testing procedure in the order of: 1) comparison of 2 mg/day brexpiprazole versus placebo, and 2) comparison of 1 mg/day brexpiprazole versus placebo.
    End point type
    Primary
    End point timeframe
    Baseline, Week 12/Early Termination (ET)
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Quantitative statistical analysis (for example, a p-value) was performed only for the Brexpiprazole 2 mg/Day, Brexpiprazole 1 mg/Day, and Placebo reporting groups.
    End point values
    		 Brexpiprazole 1 mg/day Brexpiprazole 2 mg/day Placebo
    Number of subjects analysed
    134
    138
    131
    Units: units on a scale
        least squares mean (standard error)
    -17.6 ( 1.33 )
    -21.6 ( 1.32 )
    -17.8 ( 1.34 )
    Statistical analysis title
    		 Brexpiprazole 2 mg/Day versus Placebo
    Statistical analysis description
    Change from baseline in the CMAI Total Score after 12 weeks of brexpiprazole treatment (2 mg/day) compared to 12 weeks of placebo.
    Comparison groups
    Brexpiprazole 2 mg/day v Placebo
    Number of subjects included in analysis
    269
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0404
    Method
    		 Mixed-effect model repeated measure
    Parameter type
    		 Least square (LS) mean difference
    Point estimate
    -3.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.38
         upper limit
    		 -0.17
    Statistical analysis title
    		 Brexpiprazole 1 mg/Day versus Placebo
    Statistical analysis description
    Change from baseline in the CMAI Total Score after 12 weeks of brexpiprazole treatment (1 mg/day) compared to 12 weeks of placebo.
    Comparison groups
    Brexpiprazole 1 mg/day v Placebo
    Number of subjects included in analysis
    265
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9015
    Method
    		 Mixed-effect model repeated measure
    Parameter type
    		 LS mean difference
    Point estimate
    0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 3.86

    Secondary: Change From Baseline In The Clinical Global Impression-Severity Of Illness (CGI-S) Score, As Related To Symptoms Of Agitation After 12 Weeks Of Brexpiprazole Treatment

    		 Close Top of page
    End point title
    		 Change From Baseline In The Clinical Global Impression-Severity Of Illness (CGI-S) Score, As Related To Symptoms Of Agitation After 12 Weeks Of Brexpiprazole Treatment [2]
    End point description
    To compare the efficacy of 2 fixed doses (1 mg/day and 2 mg/day) of brexpiprazole with placebo in participants with agitation associated with Alzheimer’s dementia, by the assessment of CGI-S score after 12 weeks of treatment. The CGI-S was used to rate the severity of agitation. Scores were: 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. A decrease in score indicates improvement in symptoms.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12/ET
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Quantitative statistical analysis (for example, a p-value) was performed only for the Brexpiprazole 2 mg/Day, Brexpiprazole 1 mg/Day, and Placebo reporting groups.
    End point values
    		 Brexpiprazole 1 mg/day Brexpiprazole 2 mg/day Placebo
    Number of subjects analysed
    134
    138
    131
    Units: units on a scale
        arithmetic mean (standard deviation)
    -1.04 ( 1.12 )
    -1.29 ( 1.05 )
    -1.08 ( 0.89 )
    Statistical analysis title
    		 Brexpiprazole 2 mg/Day versus Placebo
    Statistical analysis description
    Change from baseline in the CGI-S Score after 12 weeks of brexpiprazole treatment (2 mg/day) compared to 12 weeks of placebo.
    Comparison groups
    Brexpiprazole 2 mg/day v Placebo
    Number of subjects included in analysis
    269
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1566
    Method
    		 Mixed-effect model repeated measure
    Parameter type
    		 LS mean difference
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.39
         upper limit
    		 0.06
    Statistical analysis title
    		 Brexpiprazole 1 mg/Day versus Placebo
    Statistical analysis description
    Change from baseline in the CGI-S Score after 12 weeks of brexpiprazole treatment (1 mg/day) compared to 12 weeks of placebo.
    Comparison groups
    Brexpiprazole 1 mg/day v Placebo
    Number of subjects included in analysis
    265
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.444
    Method
    		 Mixed-effect model repeated measure
    Parameter type
    		 LS mean difference
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.32

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AEs) were collected throughout the study (Baseline to Week 12/ET).
    Adverse event reporting additional description
    Only participants who received at least 1 dose of study drug were analyzed for safety (Placebo N=135).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Brexpiprazole 0.5 mg/day
    Reporting group description
    		 All randomized participants received orally brexpiprazole 0.25 milligrams (mg)/day as a starting dose, which was up titrated to 0.5 mg/day. The investigational medicinal product (IMP) was administered once daily in the form of a tablet.

    Reporting group title
    Brexpiprazole 1 mg/day
    Reporting group description
    		 All randomized participants received orally brexpiprazole 0.25 mg/day as a starting dose, which was up titrated to 1 mg/day. The IMP was administered once daily in the form of a tablet.

    Reporting group title
    Brexpiprazole 2 mg/day
    Reporting group description
    		 All randomized participants received orally brexpiprazole 0.25 mg/day as a starting dose, which was up titrated to 2 mg/day. The IMP was administered once daily in the form of a tablet.

    Reporting group title
    Placebo
    Reporting group description
    		 All randomized participants received orally brexpiprazole-matching Placebo. The Placebo was administered once daily in the form of a tablet.

    Serious adverse events
    		 Brexpiprazole 0.5 mg/day Brexpiprazole 1 mg/day Brexpiprazole 2 mg/day Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 20 (25.00%)
    11 / 137 (8.03%)
    13 / 140 (9.29%)
    7 / 135 (5.19%)
         number of deaths (all causes)
    2
    2
    1
    0
         number of deaths resulting from adverse events
    2
    2
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (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
    Humerus Fracture
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (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
    Patella Fracture
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    1 / 135 (0.74%)
         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
    Vascular disorders
    Venous Thrombosis Limb
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (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
    Nervous system disorders
    Cerebrovascular Accident
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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
    Dementia Alzheimer’s Type
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    1 / 140 (0.71%)
    0 / 135 (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 / 1
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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
    Haemorrhage Intracranial
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Lacunar Infarction
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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
    Psychomotor Hyperactivity
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (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
    Seizure
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    1 / 135 (0.74%)
         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
    Syncope
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    1 / 135 (0.74%)
         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
    Transient Ischaemic Attack
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    1 / 135 (0.74%)
         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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (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
    Microcytic Anaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (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
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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
    Duodenal Ulcer Haemorrhage
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    1 / 135 (0.74%)
         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
    Pancreatitis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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
    Respiratory, thoracic and mediastinal disorders
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (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
    Obstructive Airways Disorder
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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 / 1
    0 / 0
    0 / 0
    Pneumonia Aspiration
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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 / 1
    0 / 0
    0 / 0
    Pulmonary Oedema
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (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
    Psychiatric disorders
    Abnormal Behaviour
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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
    1 / 20 (5.00%)
    1 / 137 (0.73%)
    1 / 140 (0.71%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delusion
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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
    Intentional Self-Injury
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    1 / 135 (0.74%)
         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
    Psychotic Disorder
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (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
    Infections and infestations
    Bacterial Sepsis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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
    Cellulitis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (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
    Clostridium Difficile Colitis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (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
    Encephalitis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    1 / 135 (0.74%)
         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
    Urinary Tract Infection
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 137 (0.00%)
    4 / 140 (2.86%)
    1 / 135 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    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
    		 Brexpiprazole 0.5 mg/day Brexpiprazole 1 mg/day Brexpiprazole 2 mg/day Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 20 (55.00%)
    27 / 137 (19.71%)
    43 / 140 (30.71%)
    29 / 135 (21.48%)
    Investigations
    Activated Partial Thromboplastin Time Prolonged
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Alanine Aminotransferase Increased
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Blood Creatine Phosphokinase Increased
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 137 (0.73%)
    1 / 140 (0.71%)
    0 / 135 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Blood Insulin Decreased
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood Lactate Dehydrogenase Increased
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Electrocardiogram QT Prolonged
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 137 (2.19%)
    2 / 140 (1.43%)
    1 / 135 (0.74%)
         occurrences all number
    1
    4
    2
    1
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Protein Total Decreased
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    3 / 140 (2.14%)
    2 / 135 (1.48%)
         occurrences all number
    1
    0
    3
    2
    Laceration
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 137 (0.73%)
    0 / 140 (0.00%)
    3 / 135 (2.22%)
         occurrences all number
    1
    1
    0
    3
    Orthostatic Hypotension
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 137 (0.73%)
    8 / 140 (5.71%)
    4 / 135 (2.96%)
         occurrences all number
    0
    1
    10
    6
    Headache
         subjects affected / exposed
    0 / 20 (0.00%)
    12 / 137 (8.76%)
    13 / 140 (9.29%)
    11 / 135 (8.15%)
         occurrences all number
    0
    13
    17
    16
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 137 (0.73%)
    2 / 140 (1.43%)
    0 / 135 (0.00%)
         occurrences all number
    1
    1
    2
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 137 (1.46%)
    3 / 140 (2.14%)
    3 / 135 (2.22%)
         occurrences all number
    2
    2
    3
    3
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 137 (0.73%)
    5 / 140 (3.57%)
    1 / 135 (0.74%)
         occurrences all number
    1
    1
    7
    1
    Salivary Hypersecretion
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    1 / 135 (0.74%)
         occurrences all number
    1
    0
    0
    1
    Epistaxis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    1 / 140 (0.71%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Dermatitis Allergic
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ecchymosis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 137 (1.46%)
    4 / 140 (2.86%)
    4 / 135 (2.96%)
         occurrences all number
    1
    3
    4
    4
    Insomnia
         subjects affected / exposed
    0 / 20 (0.00%)
    7 / 137 (5.11%)
    8 / 140 (5.71%)
    6 / 135 (4.44%)
         occurrences all number
    0
    10
    9
    7
    Paranoia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Infections and infestations
    Urinary Tract Infection
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 137 (1.46%)
    3 / 140 (2.14%)
    1 / 135 (0.74%)
         occurrences all number
    1
    2
    3
    1
    Metabolism and nutrition disorders
    Vitamin B12 Deficiency
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 137 (0.00%)
    0 / 140 (0.00%)
    0 / 135 (0.00%)
         occurrences all number
    1
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 May 2013
    Amendment number 1: Based on FDA feedback, the randomization ratio was changed from 1:2:2:2 to 1:1:1:1 (brexpiprazole 0.5 mg/day, brexpiprazole 1 mg/day, brexpiprazole 2 mg/day, placebo, respectively). Actigraphy and eDiary assessments were added to the protocol along with description of the use of day passes in this trial.
    16 Dec 2013
    Amendment number 2: The second amendment changes were made on the basis of adjustments to facilitate appropriate trial implementation and communication. It served to reflect clarifications and additions to study procedures intended to enhance participant safety and accuracy of data. Revised items included increasing the number of participating sites and recruitment period, clarification on consenting requirements, clarification of certain inclusion/exclusion criteria, and updates to the prohibited medication list. The amendment also added the option for participants who completed the 331-12-283 (2013-000503-17) trial to enter the 331-13-211 (2014-000424-23) safety trial.
    07 Jul 2014
    Amendment number 3: The changes were made to address the potential issue of missing data due to participants terminating early, as well as on the basis of adjustments considered important to ensure the safety of the participants enrolled and to facilitate appropriate study implementation and communication. The 0.5-mg arm was removed, which resulted in a reduction to the number of participants randomized. Noninstitutionalized participants were included with revisions to criteria and assessments for participants in this setting. The RUD scale and Mortality Assessment at Week 16 for participants who discontinued the trial early were added.
    10 Sep 2015
    Amendment number 4: The changes reflect clarifications and changes to trial procedures intended to enhance participant safety and accuracy of data as well as streamline the inclusion/exclusion criteria. The number of trial sites, as well as participating countries, was increased. Actigraphy was removed and eDiary was replaced with paper diaries. Revisions were made to the Schedule of Assessments to decrease participant burden.

    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 08:49:31 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA