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   43871   clinical trials with a EudraCT protocol, of which   7290   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:
    The switch study - efficacy of early antipsychotic switch versus maintenance in patients with schizophrenia poorly responding to two weeks of antipsychotic treatment

    Summary
    EudraCT number
    		 2009-012031-15
    Trial protocol
    		 DE   RO  
    Global end of trial date
    06 Feb 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Jun 2021
    First version publication date
    12 Jun 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    01KG0910
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01029769
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Technische Universität München, Fakultät für Medizin
    Sponsor organisation address
    Ismaninger Str. 22, München, Germany, 81675
    Public contact
    Prof. Dr. Stefan Leucht, Klinikum rechts der Isar der TU München, Klinik für Psychiatrie, 49 4140 4249, stefan.leucht@tum.de
    Scientific contact
    Prof. Dr. Stefan Leucht, Klinikum rechts der Isar der TU München, Klinik für Psychiatrie, 49 4140 4249, stefan.leucht@tum.de
    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
    10 Apr 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Feb 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Feb 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the current trial is to examine the superior effectiveness of an early switch of antipsychotic treatment in patients poorly responding to two weeks of randomized treatment with either olanzapine or amisulpride. The primary endpoint is the number of patients in remission after another six weeks of treatment after either continuing on the initially started antipsychotic or having been switched to the alternative study drug.
    Protection of trial subjects
    The conduct of this clinical study met the local legal and regulatory requirements. The study was conducted in accordance the ethical principles of Good Clinical Practice (GCP). Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. The study was regularly monitored by the Sponsor and all investigators connected to the study were GCP trained.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Feb 2010
    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
    Germany: 150
    Country: Number of subjects enrolled
    Romania: 177
    Worldwide total number of subjects
    327
    EEA total number of subjects
    327
    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)
    325
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Pre-screening processes were in place. Between 08.02.2010 and 06.02.2014 all patients were randomised.

    Pre-assignment
    Screening details
    		 Adult patients diagnosed with schizophrenia or schizoaffective disorder or a schizophrenic disorder examined with regard to ther suitability. This was followed by the 1st double-blind randomization (olanzapine- or amisulpride-arm).

    Period 1
    Period 1 title
    Phase I
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Assessor
    Blinding implementation details
    Medication was encapsulated in capsules identical in shape, colour and taste

    Arms
    Arm title
    		 Phase I amisulpride or olanzapine
    Arm description
    		 Amisulpride 200-800 mg/day or olanzapine 5-20mg/day. In phase I participants were randomised to either amisulpride (164 participants) or olanzapine (163 participants). The reason was that we wanted to rule out by the study design that any differences between switching and staying in phase II were related to the drug the participants were originally designed to in phase I. However, differences between amisulpride and olanzapine in phase I were not analysed.
    Arm type
    		 Treatment before phase of interest (phase II)

    Investigational medicinal product name
    Amisulpride
    Investigational medicinal product code
    ATC Code N05AH03
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    200-800mg/day

    Investigational medicinal product name
    Olanzapine
    Investigational medicinal product code
    ATC Code 37872.00.00
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    5-20mg/day

    Number of subjects in period 1
    		Phase I amisulpride or olanzapine
    Started
    327
    Completed
    285
    Not completed
    42
         Consent withdrawn by subject
    18
         Physician decision
    2
         Adverse event, non-fatal
    8
         Lost to follow-up
    3
         Lack of efficacy
    4
         Involuntary admission
    1
         Protocol deviation
    6
    Period 2
    Period 2 title
    Phase II
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Assessor
    Blinding implementation details
    Capsules of identical shape, colour and size

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Switch
    Arm description
    		 Non-improvers in phase I switch to the drug they were not assigned to in phase I
    Arm type
    		 Experimental

    Investigational medicinal product name
    Amisulpride
    Investigational medicinal product code
    ATC Code 37872.00.00
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Per Day: 200-800 milligram(s)

    Investigational medicinal product name
    Olanzapine
    Investigational medicinal product code
    ATC Code N05AH03
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    per day: 5-20mg milligram(s)

    Arm title
    		 Stay
    Arm description
    		 Non-improvers in phase I stay on the drug they were assigned to in phase I
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Amisulpride
    Investigational medicinal product code
    ATC Code 37872.00.00
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Daily dose: 200-800 milligram(s)

    Investigational medicinal product name
    Olanzapine
    Investigational medicinal product code
    ATC code N05AH03
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Daily dose: 5-20 milligram(s)

    Arm title
    		 Early improvers
    Arm description
    		 Early improvers in phase I continued to receive the same drug in phase II. Differences between early improvers and stayers/switchers were not analysed.
    Arm type
    		 Follow-up of early improvers

    Investigational medicinal product name
    Amisulpride
    Investigational medicinal product code
    ATC Code 37872.00.00
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Daily dose: 200-800 milligram(s)

    Investigational medicinal product name
    Olanzapine
    Investigational medicinal product code
    ATC code N05AH03
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Daily dose: 5-20 milligram(s)

    Number of subjects in period 2 [1]
    		Switch Stay Early improvers
    Started
    70
    72
    140
    Completed
    60
    55
    104
    Not completed
    10
    17
    36
         Consent withdrawn by subject
    3
    4
    12
         Physician decision
    -
    2
    -
         Administrative
    -
    -
    2
         Adverse event, non-fatal
    2
    1
    3
         suicide attempt
    1
    -
    -
         Lost to follow-up
    -
    1
    7
         Lack of efficacy
    2
    6
    5
         Protocol deviation
    2
    3
    6
         Randomisation error
    -
    -
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 3 participants were not re-randomised in phase II

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Phase I
    Reporting group description
    		 The patients were randomised to amisulpride group or olanzapine. We present the results of both drugs combined. Differences between drugs were not analysed.

    Reporting group values
    		 Phase I Total
    Number of subjects
    		 327 327
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 325 325
        From 65-84 years
    		 2 2
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 39.5 ( 11.5 ) -
    Gender categorical
    Units: Subjects
        Female
    		 154 154
        Male
    		 173 173

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Phase I amisulpride or olanzapine
    Reporting group description
    		 Amisulpride 200-800 mg/day or olanzapine 5-20mg/day. In phase I participants were randomised to either amisulpride (164 participants) or olanzapine (163 participants). The reason was that we wanted to rule out by the study design that any differences between switching and staying in phase II were related to the drug the participants were originally designed to in phase I. However, differences between amisulpride and olanzapine in phase I were not analysed.
    Reporting group title
    Switch
    Reporting group description
    		 Non-improvers in phase I switch to the drug they were not assigned to in phase I

    Reporting group title
    Stay
    Reporting group description
    		 Non-improvers in phase I stay on the drug they were assigned to in phase I

    Reporting group title
    Early improvers
    Reporting group description
    		 Early improvers in phase I continued to receive the same drug in phase II. Differences between early improvers and stayers/switchers were not analysed.

    Primary: Symptomatic remission

    		 Close Top of page
    End point title
    		 Symptomatic remission
    End point description
    Remission according to Andreasen et al. 2005 Reference: Andreasen NC, Carpenter WT Jr, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005 Mar;162(3):441-9
    End point type
    Primary
    End point timeframe
    End of phase II
    End point values
    		 Switch Stay
    Number of subjects analysed
    60 [1]
    55 [2]
    Units: Participants
    41
    25
    Notes
    [1] - The numbers presented are the phase 2 completers
    [2] - The numbers presented are the phase II completers
    Statistical analysis title
    		 Logistic regression symptomatic remission
    Statistical analysis description
    Logistic regression model with “remission” as the dependent variable and “switch” of treatment (yes/no) and PANSS-total score at visit 3 as independent variables was used. Multiple imputation (based upon 20 imputations).
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [3]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.35
         upper limit
    		 6.72
    Notes
    [3] - the result was 0.007

    Secondary: PANSS Total Score change from Switch Randomization

    		 Close Top of page
    End point title
    		 PANSS Total Score change from Switch Randomization
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    60 [4]
    55 [5]
    Units: PANSS units
        arithmetic mean (standard deviation)
    -22.8 ( 19.9 )
    -17.3 ( 15.1 )
    Notes
    [4] - Completers
    [5] - Completers
    Statistical analysis title
    		 Mixed-model of repeated measurements
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Median difference (final values)
    Point estimate
    -4.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.58
         upper limit
    		 0.51

    Secondary: Positive PANSS, Change from Switch Randomization

    		 Close Top of page
    End point title
    		 Positive PANSS, Change from Switch Randomization
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    60 [6]
    55 [7]
    Units: PANSS points
        arithmetic mean (standard deviation)
    -6.25 ( 5.22 )
    -5.96 ( 5.89 )
    Notes
    [6] - Completers
    [7] - Completers
    Statistical analysis title
    		 MMRM
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.32
         upper limit
    		 0.59

    Secondary: Negative PANSS, Change from Switch Randomization

    		 Close Top of page
    End point title
    		 Negative PANSS, Change from Switch Randomization
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    60 [8]
    55 [9]
    Units: PANSS points
        arithmetic mean (standard deviation)
    -6 ( 7.15 )
    -3.64 ( 4.7 )
    Notes
    [8] - Completers
    [9] - Completers
    No statistical analyses for this end point

    Secondary: General PANSS, change from Switch Randomization

    		 Close Top of page
    End point title
    		 General PANSS, change from Switch Randomization
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    60 [10]
    55 [11]
    Units: PANSS points
        arithmetic mean (standard deviation)
    -10.5 ( 9.8 )
    -7.75 ( 6.81 )
    Notes
    [10] - Completers
    [11] - Completers
    Statistical analysis title
    		 Mixed-model of repeated measurement
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.64
         upper limit
    		 0.77

    Secondary: CGI Severity, Change from Switch Randomization

    		 Close Top of page
    End point title
    		 CGI Severity, Change from Switch Randomization
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    60 [12]
    55 [13]
    Units: CGI points
        arithmetic mean (standard deviation)
    -1.42 ( 0.944 )
    -1.11 ( 0.956 )
    Notes
    [12] - Completers
    [13] - Completers
    Statistical analysis title
    		 MMRM
    Comparison groups
    Stay v Switch
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.64
         upper limit
    		 -0.05

    Secondary: CGI Global Improvement, Change from Switch Randomization

    		 Close Top of page
    End point title
    		 CGI Global Improvement, Change from Switch Randomization
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    60
    55 [14]
    Units: CGI points
        arithmetic mean (standard deviation)
    -1.03 ( 0.843 )
    -0.709 ( 1.01 )
    Notes
    [14] - Completers
    Statistical analysis title
    		 Continuous outcomes switchers versus stayers
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 -0.05

    Secondary: Subjective Well-Being under Neuroleptics Scale (SWN), Change from Switch Randomization

    		 Close Top of page
    End point title
    		 Subjective Well-Being under Neuroleptics Scale (SWN), Change from Switch Randomization
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    59 [15]
    55 [16]
    Units: SWN points
        arithmetic mean (standard deviation)
    8.37 ( 15.3 )
    5.85 ( 10.9 )
    Notes
    [15] - Completers
    [16] - Completers
    Statistical analysis title
    		 MMRM
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.52
         upper limit
    		 4.93

    Secondary: Psychosocial Performance Scale (PSP), Change from Switch Randomization

    		 Close Top of page
    End point title
    		 Psychosocial Performance Scale (PSP), Change from Switch Randomization
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    60 [17]
    54 [18]
    Units: PSP points
        arithmetic mean (standard deviation)
    11.8 ( 13.6 )
    10.4 ( 10.2 )
    Notes
    [17] - Completers
    [18] - Completers
    Statistical analysis title
    		 MMRM
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.98
         upper limit
    		 8.45

    Secondary: Drug Attitude Inventory (DAI), Change from Switch Randomisation

    		 Close Top of page
    End point title
    		 Drug Attitude Inventory (DAI), Change from Switch Randomisation
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    58 [19]
    54 [20]
    Units: DAI points
        arithmetic mean (standard deviation)
    1.21 ( 3.98 )
    1.04 ( 3.35 )
    Notes
    [19] - Completers
    [20] - Completers
    Statistical analysis title
    		 MMRM
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.14
         upper limit
    		 1.27

    Secondary: Riedel-Spellmann-Musil Scale Patient (RSMP), Change from Switch Randomisation

    		 Close Top of page
    End point title
    		 Riedel-Spellmann-Musil Scale Patient (RSMP), Change from Switch Randomisation
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    59 [21]
    54 [22]
    Units: RSMP points
        arithmetic mean (standard deviation)
    -0.0847 ( 8.56 )
    2.11 ( 9.5 )
    Notes
    [21] - Completers
    [22] - Completers
    Statistical analysis title
    		 MMRM
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.16
         upper limit
    		 2.04

    Secondary: Riedel-Spellmann-Musil Scale Observer (RSMO), Riedel-Spellmann-Musil Scale Patient (RSMP), Change from Switch Randomisation

    		 Close Top of page
    End point title
    		 Riedel-Spellmann-Musil Scale Observer (RSMO), Riedel-Spellmann-Musil Scale Patient (RSMP), Change from Switch Randomisation
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    58 [23]
    55 [24]
    Units: RSMO points
        arithmetic mean (standard deviation)
    0.931 ( 4.82 )
    0.509 ( 5.6 )
    Notes
    [23] - Completers
    [24] - Completers
    Statistical analysis title
    		 MMRM
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 3.08

    Secondary: Barnes Akathisia Scale, change from switch randomisation

    		 Close Top of page
    End point title
    		 Barnes Akathisia Scale, change from switch randomisation
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    60 [25]
    55 [26]
    Units: Barnes Akathisia Scale points
        arithmetic mean (standard deviation)
    -0.25 ( 1.79 )
    -0.49 ( 1.91 )
    Notes
    [25] - Completers
    [26] - Completers
    Statistical analysis title
    		 Mixed-model of repeated measurements
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.39
         upper limit
    		 0.69

    Secondary: Simpson Angus Scale, change from Switch Randomization

    		 Close Top of page
    End point title
    		 Simpson Angus Scale, change from Switch Randomization
    End point description
    End point type
    Secondary
    End point timeframe
    Change from Switch Randomization to endpoint
    End point values
    		 Switch Stay
    Number of subjects analysed
    60 [27]
    54 [28]
    Units: Simpson Angus Scale points
        arithmetic mean (standard deviation)
    -0.13 ( 2.53 )
    0.11 ( 3.35 )
    Notes
    [27] - Completers
    [28] - Completers
    Statistical analysis title
    		 Mixed-model of repeated measurement
    Comparison groups
    Switch v Stay
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.93
         upper limit
    		 1

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    For the groups "switchers phase II", "stayers phase II", "early improvers phase II": from randomization for phase II to endpoint For the group "Adverse events in phase I amisulpride and olanzapine combined": from randomization for phase I to end phase I
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Switchers phase II
    Reporting group description
    		 Randomised to switch in phase II and received at least one dose of study drug

    Reporting group title
    Stayers phase II
    Reporting group description
    		 Randomised to staying on the same drug in phase II and received at least one dose of study drug

    Reporting group title
    Early improvers phase II
    Reporting group description
    		 Improved in phase I, remained on the same study drug, and received at least one dose of study drug

    Reporting group title
    Phase I amisulpride and olanzapine combined
    Reporting group description
    		 As the comparison of amisulpride and olanzapine is not the aim of the study, we present the adverse events that occured in phase I for both groups combined

    Serious adverse events
    		 Switchers phase II Stayers phase II Early improvers phase II Phase I amisulpride and olanzapine combined
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 70 (4.29%)
    4 / 72 (5.56%)
    9 / 140 (6.43%)
    5 / 327 (1.53%)
         number of deaths (all causes)
    0
    0
    1
    0
         number of deaths resulting from adverse events
    0
    0
    1
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 327 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Lithium intoxication
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 327 (0.31%)
         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
    Pulmonary thrombosis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    0 / 327 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Worsening of psychosis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    5 / 140 (3.57%)
    2 / 327 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 5
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Affective worsening
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 327 (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
    Suicide attempt
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    0 / 327 (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
    Agitation
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    0 / 327 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic relapse
         subjects affected / exposed
    0 / 70 (0.00%)
    3 / 72 (4.17%)
    1 / 140 (0.71%)
    1 / 327 (0.31%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Switchers phase II Stayers phase II Early improvers phase II Phase I amisulpride and olanzapine combined
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    31 / 70 (44.29%)
    28 / 72 (38.89%)
    63 / 140 (45.00%)
    100 / 327 (30.58%)
    Vascular disorders
    Orthostatic hypotension
         subjects affected / exposed [1]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    0 / 325 (0.00%)
         occurrences all number
    0
    1
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed [2]
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    0 / 325 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Chills
         subjects affected / exposed [3]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    General physical health deterioration
         subjects affected / exposed [4]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Oedema peripheral
         subjects affected / exposed [5]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Pyrexia
         subjects affected / exposed [6]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    0
    2
    Reproductive system and breast disorders
    Galactorrhoea
         subjects affected / exposed [7]
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    2 / 140 (1.43%)
    0 / 325 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Menstruation delayed
         subjects affected / exposed [8]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sexual dysfunction
         subjects affected / exposed [9]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dysmenorrhoea
         subjects affected / exposed [10]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Gynaecomastia
         subjects affected / exposed [11]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Pharyngeal dyskinesia
         subjects affected / exposed [12]
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    0 / 325 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nasal congestion
         subjects affected / exposed [13]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    1
    1
    Rhinorrhoea
         subjects affected / exposed [14]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed [15]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Psychiatric disorders
    Agitation
         subjects affected / exposed [16]
    2 / 70 (2.86%)
    0 / 72 (0.00%)
    4 / 140 (2.86%)
    8 / 325 (2.46%)
         occurrences all number
    2
    0
    4
    8
    Anxiety
         subjects affected / exposed [17]
    3 / 70 (4.29%)
    1 / 72 (1.39%)
    2 / 140 (1.43%)
    5 / 325 (1.54%)
         occurrences all number
    3
    1
    2
    5
    Insomnia
         subjects affected / exposed [18]
    9 / 70 (12.86%)
    2 / 72 (2.78%)
    7 / 140 (5.00%)
    14 / 325 (4.31%)
         occurrences all number
    9
    2
    7
    14
    Irritability
         subjects affected / exposed [19]
    1 / 70 (1.43%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    0 / 325 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Psychotic disorder
         subjects affected / exposed [20]
    0 / 70 (0.00%)
    2 / 72 (2.78%)
    5 / 140 (3.57%)
    6 / 325 (1.85%)
         occurrences all number
    0
    2
    5
    6
    Restlessness
         subjects affected / exposed [21]
    1 / 70 (1.43%)
    3 / 72 (4.17%)
    3 / 140 (2.14%)
    4 / 325 (1.23%)
         occurrences all number
    1
    3
    3
    4
    Tension
         subjects affected / exposed [22]
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    3 / 325 (0.92%)
         occurrences all number
    1
    0
    0
    3
    Depression
         subjects affected / exposed [23]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    5 / 140 (3.57%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    5
    2
    Nervousness
         subjects affected / exposed [24]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sleep disorder
         subjects affected / exposed [25]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    5 / 325 (1.54%)
         occurrences all number
    0
    0
    1
    5
    Apathy
         subjects affected / exposed [26]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Catatonia
         subjects affected / exposed [27]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Confusional state
         subjects affected / exposed [28]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Disorientation
         subjects affected / exposed [29]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Drug use disorder
         subjects affected / exposed [30]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Libido increased
         subjects affected / exposed [31]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Panic attack
         subjects affected / exposed [32]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Investigations
    Electrocardiogram repolarisation abnormality
    Additional description: QT prolonged
         subjects affected / exposed [33]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    0 / 325 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hepatic enzyme increased
         subjects affected / exposed [34]
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Transaminases increased
         subjects affected / exposed [35]
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    1
    0
    0
    2
    Weight decreased
         subjects affected / exposed [36]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    3 / 325 (0.92%)
         occurrences all number
    0
    1
    0
    3
    Weight increased
         subjects affected / exposed [37]
    1 / 70 (1.43%)
    1 / 72 (1.39%)
    4 / 140 (2.86%)
    19 / 325 (5.85%)
         occurrences all number
    1
    1
    4
    19
    C-reactive protein increased
         subjects affected / exposed [38]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Alcohol poisoning
         subjects affected / exposed [39]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Toxicity to various agents
         subjects affected / exposed [40]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Cardiac disorders
    Hypotension
         subjects affected / exposed [41]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    3 / 325 (0.92%)
         occurrences all number
    0
    1
    0
    3
    Myocardial infarction
         subjects affected / exposed [42]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Myocardial ischaemia
         subjects affected / exposed [43]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Pericardial effusion
         subjects affected / exposed [44]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Tachycardia
         subjects affected / exposed [45]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    0
    2
    Nervous system disorders
    Dysaesthesia
         subjects affected / exposed [46]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    0 / 325 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Extrapyramidal disorder
         subjects affected / exposed [47]
    2 / 70 (2.86%)
    2 / 72 (2.78%)
    0 / 140 (0.00%)
    8 / 325 (2.46%)
         occurrences all number
    2
    2
    0
    8
    Headache
         subjects affected / exposed [48]
    4 / 70 (5.71%)
    1 / 72 (1.39%)
    6 / 140 (4.29%)
    7 / 325 (2.15%)
         occurrences all number
    4
    1
    6
    7
    Oromandibular dystonia
         subjects affected / exposed [49]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    0
    1
    0
    2
    Paraesthesia
         subjects affected / exposed [50]
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    0 / 325 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Parkinson gait
         subjects affected / exposed [51]
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    0 / 325 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychomotor hyperactivity
         subjects affected / exposed [52]
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    2 / 140 (1.43%)
    1 / 325 (0.31%)
         occurrences all number
    1
    0
    2
    1
    Sedation
         subjects affected / exposed [53]
    3 / 70 (4.29%)
    2 / 72 (2.78%)
    6 / 140 (4.29%)
    15 / 325 (4.62%)
         occurrences all number
    3
    2
    6
    15
    Somnolence
         subjects affected / exposed [54]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    1 / 140 (0.71%)
    3 / 325 (0.92%)
         occurrences all number
    0
    1
    1
    3
    Tremor
         subjects affected / exposed [55]
    4 / 70 (5.71%)
    2 / 72 (2.78%)
    8 / 140 (5.71%)
    17 / 325 (5.23%)
         occurrences all number
    4
    2
    8
    17
    Akathisia
         subjects affected / exposed [56]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    7 / 140 (5.00%)
    13 / 325 (4.00%)
         occurrences all number
    0
    0
    7
    13
    Dizziness
         subjects affected / exposed [57]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    2 / 140 (1.43%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    2
    2
    Dystonia
         subjects affected / exposed [58]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    1
    2
    Hypokinesia
         subjects affected / exposed [59]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    3 / 325 (0.92%)
         occurrences all number
    0
    0
    1
    3
    Dyskinesia
         subjects affected / exposed [60]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    0
    2
    Syncope
         subjects affected / exposed [61]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Leukocytosis
         subjects affected / exposed [62]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed [63]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Eye disorders
    Vision blurred
         subjects affected / exposed [64]
    1 / 70 (1.43%)
    2 / 72 (2.78%)
    2 / 140 (1.43%)
    1 / 325 (0.31%)
         occurrences all number
    1
    2
    2
    1
    accomodation disorder
         subjects affected / exposed [65]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    0
    2
    Dry eye
         subjects affected / exposed [66]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed [67]
    2 / 70 (2.86%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    6 / 325 (1.85%)
         occurrences all number
    2
    0
    0
    6
    Dry mouth
         subjects affected / exposed [68]
    1 / 70 (1.43%)
    2 / 72 (2.78%)
    4 / 140 (2.86%)
    5 / 325 (1.54%)
         occurrences all number
    1
    2
    4
    5
    Nausea
         subjects affected / exposed [69]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    4 / 325 (1.23%)
         occurrences all number
    0
    1
    0
    4
    Salivary hypersecretion
         subjects affected / exposed [70]
    1 / 70 (1.43%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    3 / 325 (0.92%)
         occurrences all number
    1
    0
    1
    3
    Vomiting
         subjects affected / exposed [71]
    1 / 70 (1.43%)
    1 / 72 (1.39%)
    2 / 140 (1.43%)
    1 / 325 (0.31%)
         occurrences all number
    1
    1
    2
    1
    Abdominal discomfort
         subjects affected / exposed [72]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Abdominal pain upper
         subjects affected / exposed [73]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    0
    2
    Dyspepsia
         subjects affected / exposed [74]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Dysphagia
         subjects affected / exposed [75]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    0
    2
    Gastritis
         subjects affected / exposed [76]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Toothache
         subjects affected / exposed [77]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    3 / 325 (0.92%)
         occurrences all number
    0
    0
    0
    3
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed [78]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Alopecia
         subjects affected / exposed [79]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rash
         subjects affected / exposed [80]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dermal cyst
         subjects affected / exposed [81]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Eczema
         subjects affected / exposed [82]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    0
    2
    Hyperhidrosis
         subjects affected / exposed [83]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    0
    2
    Endocrine disorders
    Hyperprolactinaemia
         subjects affected / exposed [84]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    0 / 325 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed [85]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    1
    0
    1
    Muscle rigidity
         subjects affected / exposed [86]
    2 / 70 (2.86%)
    2 / 72 (2.78%)
    4 / 140 (2.86%)
    10 / 325 (3.08%)
         occurrences all number
    2
    2
    4
    10
    Arthralgia
         subjects affected / exposed [87]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Bursitis
         subjects affected / exposed [88]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Limb discomfort
         subjects affected / exposed [89]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Torticollis
         subjects affected / exposed [90]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Infections and infestations
    Tooth infection
         subjects affected / exposed [91]
    0 / 70 (0.00%)
    1 / 72 (1.39%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    1
    0
    1
    Febrile infection
         subjects affected / exposed [92]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Furuncle
         subjects affected / exposed [93]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    0 / 325 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vaginal infection
         subjects affected / exposed [94]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    3 / 325 (0.92%)
         occurrences all number
    0
    0
    1
    3
    Nasopharyngitis
         subjects affected / exposed [95]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    4 / 325 (1.23%)
         occurrences all number
    0
    0
    0
    4
    Pharyngitis
         subjects affected / exposed [96]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Respiratory tract infection viral
         subjects affected / exposed [97]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed [98]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    2 / 325 (0.62%)
         occurrences all number
    0
    0
    0
    2
    Viral rhinitis
         subjects affected / exposed [99]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Increased appetite
         subjects affected / exposed [100]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    1 / 140 (0.71%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    1
    1
    Decreased appetite
         subjects affected / exposed [101]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed [102]
    0 / 70 (0.00%)
    0 / 72 (0.00%)
    0 / 140 (0.00%)
    1 / 325 (0.31%)
         occurrences all number
    0
    0
    0
    1
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [25] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [26] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [27] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [28] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [29] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [30] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [31] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [32] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [33] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [34] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [35] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [36] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [37] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [38] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [39] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [40] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [41] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [42] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [43] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [44] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [45] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [46] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [47] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [48] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [49] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [50] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [51] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [52] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [53] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [54] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [55] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [56] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [57] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [58] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [59] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [60] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [61] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [62] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [63] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [64] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [65] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [66] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [67] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [68] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [69] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [70] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [71] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [72] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [73] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [74] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [75] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [76] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [77] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [78] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [79] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [80] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [81] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [82] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [83] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [84] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [85] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [86] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [87] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [88] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [89] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [90] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [91] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [92] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [93] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [94] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [95] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [96] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [97] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [98] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [99] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [100] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [101] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population
    [102] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: 2 participants did not receive study drug and were therefore excluded from the safety population

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Mar 2010
    supply of olanzapine medication by EliLilly, specification of inclusion criteria, qualification and training of study personal concerning examination with the Positive and Negative Syndrome Scale, specification of date for blood measurement, specification of randomisation and treatment allocation, specification in terms of prolactin levels, deletion of AIMS scale, amendment and specification of rescue medication
    07 Oct 2010
    dosing of olanzapine and amisulpride in the first 3 days, amendment of the exclusion criterion patients under guardianship, specification of the relevance of the pregnancy test at screening, specification about laboratory values as adverse events, specification of drug accountability, specification about destruction of study medication, prolongation of follow-up period, specification about inclusion criterion increase in level of care, specification of pre-study treatment, correction of writing error in protocol
    14 Sep 2011
    inclusion of patients with legal guardianship, specification of exclusion criterion sufficient dose of study drugs before the study, definition of a time window for visits, end of electronic documentation of study data with electronic CRF, formal changes
    09 Nov 2012
    expansion of the study to Romania, specification of pseudonymisation of Romanian participants, registration of the study in Romania, participant insurance for Romania, procedure in the case of protocol changes, change of the run time of the study, number of centers in Germany, amendment of measurement of body size in the protocol, exclusion of participants with legal guardianship in Romania

    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.
    The data of one site which violated good clinical practice in other trials were excluded.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/26227799
    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-Fri May 03 23:13:57 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA