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    Clinical Trial Results:
    A Phase III, Randomized, Double-Blind, Placebo-Controlled, Adaptive Design Study of the Efficacy, Safety, and Tolerability of a Single Infusion of MK-3415 (Human Monoclonal Antibody to Clostridium difficile toxin A), MK-6072 (Human Monoclonal Antibody to Clostridium difficile toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium difficile toxin A and toxin B) in Patients Receiving Antibiotic Therapy for Clostridium difficile Infection (MODIFY I)

    Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
    Summary
    EudraCT number
    		 2011-004590-90
    Trial protocol
    		 DE   ES   CZ   BE   DK   PT   AT   IT   GB  
    Global end of trial date
    09 Dec 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Feb 2016
    First version publication date
    06 Feb 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    3415A-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01241552
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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
    09 Dec 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    09 Dec 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Dec 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary Objective #1 (at interim analysis) and #2 (at final analysis): To determine if treatment with a single infusion of combined monoclonal antibody therapy (MK-3415A) with standard of care therapy decreases the proportion of participants with CDI recurrence over a period of 12 weeks as compared to treatment with a single infusion of individual monoclonal antibody therapy (MK-3415 or MK-6072) with standard of care therapy. Primary Objective #3: To determine if treatment with a single infusion of monoclonal antibody therapy with standard of care therapy (combined monoclonal antibody therapy [MK-3415A] and possibly the separate individual monoclonal antibody therapy [MK-3415 and/or MK-6072]) decreases the proportion of participants with CDI recurrence over a period of 12 weeks as compared to treatment with a single infusion of placebo with standard of care therapy.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 Oral SOC antibiotic therapy (metronidazole, vancomycin, or fidaxomicin) for a primary or recurrent episode of CDI.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Oct 2011
    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
    Australia: 52
    Country: Number of subjects enrolled
    Austria: 18
    Country: Number of subjects enrolled
    Belgium: 28
    Country: Number of subjects enrolled
    Brazil: 11
    Country: Number of subjects enrolled
    Canada: 89
    Country: Number of subjects enrolled
    Chile: 55
    Country: Number of subjects enrolled
    Colombia: 23
    Country: Number of subjects enrolled
    Czech Republic: 34
    Country: Number of subjects enrolled
    Denmark: 69
    Country: Number of subjects enrolled
    Germany: 31
    Country: Number of subjects enrolled
    Israel: 85
    Country: Number of subjects enrolled
    Italy: 82
    Country: Number of subjects enrolled
    Mexico: 8
    Country: Number of subjects enrolled
    New Zealand: 22
    Country: Number of subjects enrolled
    Portugal: 25
    Country: Number of subjects enrolled
    South Africa: 10
    Country: Number of subjects enrolled
    Spain: 85
    Country: Number of subjects enrolled
    United Kingdom: 37
    Country: Number of subjects enrolled
    United States: 688
    Worldwide total number of subjects
    1452
    EEA total number of subjects
    409
    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)
    721
    From 65 to 84 years
    581
    85 years and over
    150

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants 18 years of age or older, with a diagnosis of CDI were enrolled in this trial.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MK-3415 + SOC
    Arm description
    		 Single intravenous (IV) infusion of 10 mg/kg MK-3415 + SOC for CDI
    Arm type
    		 Experimental

    Investigational medicinal product name
    MK-3415
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single IV infusion of MK-3415 (10 mg/kg of monoclonal antibody to Clostridium difficile Toxin A)

    Investigational medicinal product name
    SOC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    SOC for CDI was antibiotic therapy consisting of metronidazole, vancomycin, or fidaxomicin prescribed for 10 to 14 days beginning prior to or on the day of study drug

    Arm title
    		 MK-6072+ SOC
    Arm description
    		 Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI
    Arm type
    		 Experimental

    Investigational medicinal product name
    MK-6072
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single IV infusion of MK-6072 (10 mg/kg of monoclonal antibody to Clostridium difficile Toxin B)

    Investigational medicinal product name
    SOC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    SOC for CDI was antibiotic therapy consisting of metronidazole, vancomycin, or fidaxomicin prescribed for 10 to 14 days beginning prior to or on the day of study drug

    Arm title
    		 MK-3415A + SOC
    Arm description
    		 Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI
    Arm type
    		 Experimental

    Investigational medicinal product name
    SOC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    SOC for CDI was antibiotic therapy consisting of metronidazole, vancomycin, or fidaxomicin prescribed for 10 to 14 days beginning prior to or on the day of study drug

    Investigational medicinal product name
    MK-3415A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single IV infusion of MK3415A (10 mg/kg of monoclonal antibody to Clostridium difficile Toxin A and 10mg/kg of monoclonal antibody to Clostridium difficile Toxin B)

    Arm title
    		 Placebo Comparator + SOC
    Arm description
    		 Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single IV infusion of normal saline (0.9% sodium chloride)

    Investigational medicinal product name
    SOC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    SOC for CDI was antibiotic therapy consisting of metronidazole, vancomycin, or fidaxomicin prescribed for 10 to 14 days beginning prior to or on the day of study drug

    Number of subjects in period 1
    		MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Started
    242
    403
    403
    404
    Treated
    235
    392
    388
    397
    Completed
    201
    340
    343
    340
    Not completed
    41
    63
    60
    64
         Consent withdrawn by subject
    7
    15
    14
    15
         Physician decision
    2
    4
    2
    3
         Adverse event, non-fatal
    1
    1
    -
    -
         Death
    26
    30
    20
    25
         Technical Problems
    2
    -
    2
    2
         Progressive Disease
    -
    -
    1
    2
         Lost to follow-up
    2
    11
    15
    16
         Lack of efficacy
    1
    -
    -
    -
         Protocol deviation
    -
    2
    6
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MK-3415 + SOC
    Reporting group description
    		 Single intravenous (IV) infusion of 10 mg/kg MK-3415 + SOC for CDI

    Reporting group title
    MK-6072+ SOC
    Reporting group description
    		 Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI

    Reporting group title
    MK-3415A + SOC
    Reporting group description
    		 Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI

    Reporting group title
    Placebo Comparator + SOC
    Reporting group description
    		 Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI

    Reporting group values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC Total
    Number of subjects
    		 242 403 403 404 1452
    Age Categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 117 210 195 199 721
        From 65-84 years
    		 92 153 178 158 581
        85 years and over
    		 33 40 30 47 150
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.2 ± 16.8 61.1 ± 18.5 62.5 ± 17.8 62.9 ± 18.3 -
    Gender Categorical
    Units: Subjects
        Female
    		 137 238 224 230 829
        Male
    		 105 165 179 174 623

    End points

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    End points reporting groups
    Reporting group title
    MK-3415 + SOC
    Reporting group description
    		 Single intravenous (IV) infusion of 10 mg/kg MK-3415 + SOC for CDI

    Reporting group title
    MK-6072+ SOC
    Reporting group description
    		 Single IV infusion of 10 mg/kg MK-6072 + Standard of Care for CDI

    Reporting group title
    MK-3415A + SOC
    Reporting group description
    		 Single IV infusion of 10 mg/kg MK-3415A + Standard of Care for CDI

    Reporting group title
    Placebo Comparator + SOC
    Reporting group description
    		 Normal saline infusion (0.9% sodium chloride) + Standard of Care for CDI

    Primary: Percentage of participants with CDI recurrence

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    End point title
    		 Percentage of participants with CDI recurrence
    End point description
    CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. The population analyzed consisted of participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.
    End point type
    Primary
    End point timeframe
    Up to 12 weeks
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    232
    386
    383
    395
    Units: Percentage of participants
        number (not applicable)
    25.9
    17.4
    15.9
    27.6
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    627
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3182 [1]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.6
         upper limit
    		 5.5
    Notes
    [1] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    781
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0003 [2]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -10.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.9
         upper limit
    		 -4.3
    Notes
    [2] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [3]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -11.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.4
         upper limit
    		 -5.9
    Notes
    [3] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415A + SOC - MK-3415 + SOC
    Comparison groups
    MK-3415 + SOC v MK-3415A + SOC
    Number of subjects included in analysis
    615
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0013 [4]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -9.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.9
         upper limit
    		 -3.4
    Notes
    [4] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415A + SOC - MK-6072 + SOC
    Comparison groups
    MK-6072+ SOC v MK-3415A + SOC
    Number of subjects included in analysis
    769
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2997 [5]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.7
         upper limit
    		 3.9
    Notes
    [5] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).

    Primary: Percentage of participants with one or more Adverse Events (AEs) during 4 weeks following infusion

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    End point title
    		 Percentage of participants with one or more Adverse Events (AEs) during 4 weeks following infusion
    End point description
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol-specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. The population analyzed consisted of all randomized participants who received infusion of study medication.
    End point type
    Primary
    End point timeframe
    Up to 28 days
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    235
    390
    387
    400
    Units: Percentage of participants
        number (not applicable)
    67.2
    65.4
    59.7
    62
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.185
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    5.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.5
         upper limit
    		 12.8
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    790
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.323
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 10.1
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    787
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.507
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    -2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.1
         upper limit
    		 4.5

    Primary: Percentage of participants with any drug-related AE during 4 weeks following infusion

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    End point title
    		 Percentage of participants with any drug-related AE during 4 weeks following infusion
    End point description
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol-specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. A drug-related AE was an AE determined by the investigator to be related to the drug. The population analyzed consisted of all randomized participants who received infusion of study medication.
    End point type
    Primary
    End point timeframe
    Up to 28 days
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    235
    390
    387
    400
    Units: Percentage of participants
        number (not applicable)
    7.2
    8.2
    6.2
    5
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.246
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 6.7
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    790
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.069
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    3.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 6.8
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    787
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.464
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 4.6

    Primary: Percentage of participants with any serious adverse events (SAEs) during 4 weeks following infusion

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    End point title
    		 Percentage of participants with any serious adverse events (SAEs) during 4 weeks following infusion
    End point description
    A SAE is any AE occurring at any dose or during any use of Sponsor’s product that: results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer, or is associated with an overdose (whether accidental or intentional); or is other important medical events. The population analyzed consisted of all randomized participants who received infusion of study medication
    End point type
    Primary
    End point timeframe
    Up to 28 days
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    235
    390
    387
    400
    Units: Percentage of participants
        number (not applicable)
    27.7
    21.5
    14.7
    20
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.027
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    7.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 14.7
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    790
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.594
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.1
         upper limit
    		 7.2
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    787
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.051
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    -5.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.6
         upper limit
    		 0

    Primary: Percentage of participants with any serious drug-related AEs (SAEs) during 4 weeks following infusion

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    End point title
    		 Percentage of participants with any serious drug-related AEs (SAEs) during 4 weeks following infusion
    End point description
    A SAE is any AE occurring at any dose or during any use of Sponsor’s product that: results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer, or is associated with an overdose (whether accidental or intentional); or is other important medical events. A serious drug-related AE was an SAE determined by the investigator to be related to the drug. The population analyzed consisted of all randomized participants who received infusion of study medication
    End point type
    Primary
    End point timeframe
    Up to 28 days
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    235
    390
    387
    400
    Units: Percentage of participants
        number (not applicable)
    1.3
    1
    0.5
    0.3
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.115
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 3.5
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    790
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.17
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 2.4
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    787
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.544
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 1.6

    Primary: Percentage of participants who discontinued study medication due to an AE during 4 weeks following infusion

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    End point title
    		 Percentage of participants who discontinued study medication due to an AE during 4 weeks following infusion
    End point description
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended signs (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specific procedure, whether or not considered related to the medicinal product or protocol-specific procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. The population analyzed consisted of all randomized participants who received infusion of study medication.
    End point type
    Primary
    End point timeframe
    Up to 28 days
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    235
    390
    387
    400
    Units: Percentage of participants
        number (not applicable)
    0.4
    0.3
    0
    0
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.192
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 2.4
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    790
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.311
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 1.4
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    787
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.999
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Percentage Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1

    Secondary: Percentage of participants with infusion-specific AEs

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    End point title
    		 Percentage of participants with infusion-specific AEs
    End point description
    Infusion-specific AEs included local infusion site AEs; and systemic AEs which include nausea, vomiting, chills, fatigue, feeling hot, infusion site conditions (bruising, coldness, erythema, extravasation, pain, phlebitis, pruritus), pyrexia, arthralgia, musculoskeletal pain, myalgia, dizziness, headache, dysphonia, nasal congestion, pruritus, rash, pruritic rash, urticaria, flushing, hot flush, hypertension, andhypotension. The population analyzed consisted of all randomized participants who received infusion of study medication.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    235
    390
    387
    400
    Units: Percentage of participants
        number (not applicable)
    11.1
    11.8
    8.8
    7.5
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 8.7
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    790
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    4.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 8.5
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    787
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.6
         upper limit
    		 5.2

    Secondary: Percentage of participants with Global Cure

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    End point title
    		 Percentage of participants with Global Cure
    End point description
    Global Cure is defined as the clinical cure of the initial CDI episode and no CDI recurrence through Week 12. Clinical cure is defined as participants who received ≤ 14 day regimen of SOC therapy and have no diarrhea (≤2 loose stools per 24 hours) for two consecutive days following completion of SOC therapy for the baseline CDI episode. The population analyzed consisted of participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    232
    386
    383
    395
    Units: Percentage of participants
        number (not applicable)
    47
    60.1
    58.7
    55.2
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    627
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9775 [6]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -8.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.3
         upper limit
    		 -0.2
    Notes
    [6] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    781
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0861 [7]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    4.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 11.7
    Notes
    [7] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1646 [8]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.5
         upper limit
    		 10.4
    Notes
    [8] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415A + SOC - MK-3415 + SOC
    Comparison groups
    MK-3415 + SOC v MK-3415A + SOC
    Number of subjects included in analysis
    615
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0025 [9]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    11.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.5
         upper limit
    		 19.7
    Notes
    [9] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415A + SOC - MK-6072 + SOC
    Comparison groups
    MK-6072+ SOC v MK-3415A + SOC
    Number of subjects included in analysis
    769
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6532 [10]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.3
         upper limit
    		 5.5
    Notes
    [10] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).

    Secondary: Percentage of participants with CDI recurrence in those with clinical cure of the initial CDI episode

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    End point title
    		 Percentage of participants with CDI recurrence in those with clinical cure of the initial CDI episode
    End point description
    CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Clinical cure is defined as participants who received ≤ 14 day regimen of SOC therapy and have no diarrhea (≤2 loose stools per 24 hours) for two consecutive days following completion of SOC therapy for the baseline CDI episode. The population analyzed consisted of participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    169
    299
    286
    327
    Units: Percentage of participants
        number (not applicable)
    35.5
    22.4
    21.3
    33.3
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    496
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6505 [11]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.9
         upper limit
    		 10.7
    Notes
    [11] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    626
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0013 [12]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -10.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.7
         upper limit
    		 -3.8
    Notes
    [12] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    613
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0006 [13]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -11.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.6
         upper limit
    		 -4.7
    Notes
    [13] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415A + SOC - MK-3415 + SOC
    Comparison groups
    MK-3415 + SOC v MK-3415A + SOC
    Number of subjects included in analysis
    455
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0007 [14]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -13.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.5
         upper limit
    		 -5.2
    Notes
    [14] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Adjusted Difference: MK-3415A + SOC - MK-6072 + SOC
    Comparison groups
    MK-6072+ SOC v MK-3415A + SOC
    Number of subjects included in analysis
    585
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3906 [15]
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Adjusted Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.7
         upper limit
    		 5.8
    Notes
    [15] - One sided p-value based on the Miettinen and Nurminen method stratified by SOC therapy (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient).

    Secondary: Percentage of participants ≥ 65 years of age at study entry with CDI recurrence

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    End point title
    		 Percentage of participants ≥ 65 years of age at study entry with CDI recurrence
    End point description
    CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. The population analyzed consisted of participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    122
    185
    200
    199
    Units: Percentage of participants
        number (not applicable)
    26.2
    15.1
    17
    33.2
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    321
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -6.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.8
         upper limit
    		 3.5
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    384
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.3
         upper limit
    		 -9.6
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    399
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -16.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.5
         upper limit
    		 -7.7

    Secondary: Percentage of participants with a history of CDI in the 6 months prior to enrollment with CDI recurrence

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    End point title
    		 Percentage of participants with a history of CDI in the 6 months prior to enrollment with CDI recurrence
    End point description
    CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. The population analyzed consisted of participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    69
    103
    96
    109
    Units: Percentage of participants
        number (not applicable)
    33.3
    26.2
    25
    39.4
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    178
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -6.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.1
         upper limit
    		 8.6
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -13.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.5
         upper limit
    		 -0.5
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -14.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.8
         upper limit
    		 -1.6

    Secondary: Percentage of participants with clinically severe CDI at study entry with CDI recurrence

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    End point title
    		 Percentage of participants with clinically severe CDI at study entry with CDI recurrence
    End point description
    CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. With clinically severe CDI is defined as a Zar Score ≥ 2. The population analyzed consisted of participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    31
    67
    62
    60
    Units: Percentage of participants
        number (not applicable)
    25.8
    10.4
    12.9
    25
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.9
         upper limit
    		 21
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -14.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.3
         upper limit
    		 -1.4
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -12.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.2
         upper limit
    		 1.9

    Secondary: Percentage of participants with the B1/NAP1/027 strain of C. difficile at study entry with CDI recurrence

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    End point title
    		 Percentage of participants with the B1/NAP1/027 strain of C. difficile at study entry with CDI recurrence
    End point description
    CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. The population analyzed consisted of participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    24
    46
    37
    36
    Units: Percentage of participants
        number (not applicable)
    33.3
    26.1
    10.8
    36.1
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.1
         upper limit
    		 10
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -25.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -43.7
         upper limit
    		 -6.1

    Secondary: Percentage of participants infected with an epidemic strain of C. difficile (ribotypes 027, 014, 002, 001, 106, and 020) at study entry with CDI recurrence

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    End point title
    		 Percentage of participants infected with an epidemic strain of C. difficile (ribotypes 027, 014, 002, 001, 106, and 020) at study entry with CDI recurrence
    End point description
    CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. The population analyzed consisted of participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    57
    108
    106
    106
    Units: Percentage of participants
        number (not applicable)
    24.6
    23.1
    19.8
    35.8
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    163
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -11.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.9
         upper limit
    		 3.9
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -12.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.7
         upper limit
    		 -0.5
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.8
         upper limit
    		 -4

    Secondary: Percentage of participants with compromised immunity at study entry with CDI recurrence

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    End point title
    		 Percentage of participants with compromised immunity at study entry with CDI recurrence
    End point description
    CDI recurrence is defined as the development of a new episode of diarrhea (3 or more loose stools in 24 or fewer hours) and a positive local or central lab stool test for toxigenic C. difficile following clinical cure of the initial CDI episode. Compromised immunity is defined as follows: an active hematological malignancy (including leukemia, lymphoma, multiple myeloma), an active malignancy requiring recent cytotoxic chemotherapy, receipt of a prior hematopoietic stem cell transplant, receipt of a prior solid organ transplant, asplenia, or neutropenia/pancytopenia due to other conditions. The population analyzed consisted of participants who received infusion of study medication; had a positive local stool test for toxigenic C. difficile; received protocol defined standard of care therapy within 1 day window of the infusion; and complied with Good Clinical Practice.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    End point values
    		 MK-3415 + SOC MK-6072+ SOC MK-3415A + SOC Placebo Comparator + SOC
    Number of subjects analysed
    55
    87
    78
    92
    Units: Percentage of participants
        number (not applicable)
    18.2
    17.2
    11.5
    28.3
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415 + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -10.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.2
         upper limit
    		 4.6
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-6072 + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-6072+ SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    179
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.2
         upper limit
    		 1.4
    Statistical analysis title
    		 Comparison of Treatment Groups
    Statistical analysis description
    Percentage Difference: MK-3415A + SOC - Placebo Comparator + SOC
    Comparison groups
    MK-3415A + SOC v Placebo Comparator + SOC
    Number of subjects included in analysis
    170
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Percentage Difference
    Point estimate
    -16.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.4
         upper limit
    		 -4.7

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 90 days
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    MK-3415
    Reporting group description
    		 -

    Reporting group title
    MK-3415A
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    MK-6072
    Reporting group description
    		 -

    Serious adverse events
    		 MK-3415 MK-3415A Placebo MK-6072
    Total subjects affected by serious adverse events
         subjects affected / exposed
    104 / 235 (44.26%)
    94 / 387 (24.29%)
    126 / 400 (31.50%)
    120 / 390 (30.77%)
         number of deaths (all causes)
    27
    20
    26
    31
         number of deaths resulting from adverse events
    0
    1
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Acute myeloid leukaemia recurrent
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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 / 1
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Breast cancer
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Breast cancer metastatic
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Burkitt's lymphoma
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Colon cancer metastatic
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Gastric cancer
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Hypergammaglobulinaemia benign monoclonal
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Malignant melanoma
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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 / 1
    Malignant melanoma in situ
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Metastases to spine
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Ovarian cancer metastatic
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Hypertension
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Hypertensive crisis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    2 / 400 (0.50%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Peripheral artery thrombosis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Peripheral ischaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Adverse drug reaction
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Asthenia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Chest pain
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    2 / 400 (0.50%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
    General physical health deterioration
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Hernia obstructive
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Malaise
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Multi-organ failure
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    2 / 400 (0.50%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Peripheral swelling
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Sudden death
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    2 / 400 (0.50%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Immune system disorders
    Acute graft versus host disease
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Acute graft versus host disease in intestine
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Graft versus host disease
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Graft versus host disease in gastrointestinal tract
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Heart transplant rejection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Acute respiratory failure
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Aspiration
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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 / 1
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Atelectasis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 235 (0.85%)
    2 / 387 (0.52%)
    1 / 400 (0.25%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    Chronic respiratory failure
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Cough
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Hypoxia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Pharyngeal stenosis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Pleural effusion
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    3 / 400 (0.75%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    2 / 400 (0.50%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary cavitation
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Pulmonary embolism
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Pulmonary oedema
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 387 (0.52%)
    0 / 400 (0.00%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Respiratory failure
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 387 (0.26%)
    4 / 400 (1.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 2
    Sputum increased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Psychiatric disorders
    Affective disorder
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Aggression
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Alcoholism
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Confusional state
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Depression
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug dependence
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    2 / 400 (0.50%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychogenic seizure
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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 bilirubin increased
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Haemoglobin decreased
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Heart rate increased
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Platelet count decreased
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Injury, poisoning and procedural complications
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Contusion
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Fall
         subjects affected / exposed
    1 / 235 (0.43%)
    3 / 387 (0.78%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Hip fracture
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal anastomosis complication
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Perinephric collection
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Post-traumatic pain
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Procedural vomiting
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Radiation oesophagitis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Rib fracture
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    2 / 400 (0.50%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Angina unstable
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Atrial fibrillation
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Atrial tachycardia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Bradycardia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Bundle branch block left
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Cardiac arrest
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    Cardiac disorder
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Cardiac failure
         subjects affected / exposed
    3 / 235 (1.28%)
    1 / 387 (0.26%)
    4 / 400 (1.00%)
    4 / 390 (1.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Cardiac failure chronic
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    2 / 235 (0.85%)
    3 / 387 (0.78%)
    2 / 400 (0.50%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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 / 1
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    2 / 400 (0.50%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    Hypertensive heart disease
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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 / 1
    Intrapericardial thrombosis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Myocardial infarction
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Palpitations
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Sinus arrhythmia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Tachycardia
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachyarrhythmia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Cerebral infarction
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Cerebrovascular accident
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    Convulsion
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Disturbance in attention
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Encephalopathy
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Epilepsy
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Headache
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Partial seizures
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Presyncope
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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 / 1
    Syncope
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Febrile neutropenia
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 387 (0.52%)
    1 / 400 (0.25%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Leukocytosis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Neutropenia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Pancytopenia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Thrombocytopenia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Hearing impaired
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Abdominal hernia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Abdominal pain
         subjects affected / exposed
    4 / 235 (1.70%)
    4 / 387 (1.03%)
    2 / 400 (0.50%)
    3 / 390 (0.77%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Abdominal pain upper
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Acute abdomen
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Colitis ulcerative
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Constipation
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    6 / 235 (2.55%)
    6 / 387 (1.55%)
    6 / 400 (1.50%)
    9 / 390 (2.31%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 8
    0 / 7
    1 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea haemorrhagic
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Diverticular perforation
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Diverticulum
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epiploic appendagitis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Faecal incontinence
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Gastritis alcoholic
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    2 / 400 (0.50%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Haematochezia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Hernial eventration
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Ileus
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Incarcerated umbilical hernia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Inflammatory bowel disease
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Intestinal dilatation
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Intestinal obstruction
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Large intestine perforation
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Melaena
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Nausea
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Pancreatitis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Pancreatitis acute
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    2 / 400 (0.50%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis necrotising
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Proctalgia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Rectal haemorrhage
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 387 (0.52%)
    1 / 400 (0.25%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 235 (0.00%)
    3 / 387 (0.78%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Cholecystitis acute
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Cholelithiasis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Cirrhosis alcoholic
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Hepatorenal syndrome
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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 / 1
    Portal vein thrombosis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Skin and subcutaneous tissue disorders
    Ecchymosis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Eczema
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Rash
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Renal and urinary disorders
    Bladder dilatation
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Haematuria
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephritis autoimmune
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Renal failure acute
         subjects affected / exposed
    3 / 235 (1.28%)
    3 / 387 (0.78%)
    6 / 400 (1.50%)
    5 / 390 (1.28%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 2
    Renal failure chronic
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    3 / 390 (0.77%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    Renal impairment
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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 retention
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Musculoskeletal and connective tissue disorders
    Compartment syndrome
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Connective tissue disorder
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Flank pain
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Rhabdomyolysis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Spinal disorder
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Abdominal abscess
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    2 / 400 (0.50%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Arthritis bacterial
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Bacteraemia
         subjects affected / exposed
    1 / 235 (0.43%)
    3 / 387 (0.78%)
    3 / 400 (0.75%)
    3 / 390 (0.77%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Bronchitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Bronchitis viral
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Bronchopneumonia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Bursitis infective
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Campylobacter gastroenteritis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Candida infection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Cellulitis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    3 / 400 (0.75%)
    3 / 390 (0.77%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    26 / 235 (11.06%)
    18 / 387 (4.65%)
    26 / 400 (6.50%)
    10 / 390 (2.56%)
         occurrences causally related to treatment / all
    0 / 28
    0 / 21
    0 / 32
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile sepsis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Device related infection
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Device related sepsis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    2 / 400 (0.50%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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 viral
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Erysipelas
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Gangrene
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Gas gangrene
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Gastroenteritis
         subjects affected / exposed
    0 / 235 (0.00%)
    3 / 387 (0.78%)
    1 / 400 (0.25%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Graft infection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Histoplasmosis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Hypopyon
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Infected lymphocele
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Kidney infection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Lobar pneumonia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Localised infection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Mediastinitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Osteomyelitis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Pneumonia
         subjects affected / exposed
    7 / 235 (2.98%)
    5 / 387 (1.29%)
    11 / 400 (2.75%)
    7 / 390 (1.79%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
    0 / 11
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 2
    Pneumonia bacterial
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Pneumonia haemophilus
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Post procedural infection
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Postoperative wound infection
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 387 (0.52%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psoas abscess
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Pyelonephritis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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 / 1
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Salmonellosis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Sepsis
         subjects affected / exposed
    9 / 235 (3.83%)
    3 / 387 (0.78%)
    11 / 400 (2.75%)
    7 / 390 (1.79%)
         occurrences causally related to treatment / all
    0 / 9
    1 / 3
    0 / 11
    1 / 7
         deaths causally related to treatment / all
    0 / 7
    1 / 1
    0 / 3
    0 / 3
    Septic shock
         subjects affected / exposed
    3 / 235 (1.28%)
    4 / 387 (1.03%)
    4 / 400 (1.00%)
    3 / 390 (0.77%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
    0 / 3
    Soft tissue infection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Systemic candida
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Systemic mycosis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Tracheitis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Tracheobronchitis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    2 / 400 (0.50%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    6 / 235 (2.55%)
    4 / 387 (1.03%)
    5 / 400 (1.25%)
    6 / 390 (1.54%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    2 / 400 (0.50%)
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Zygomycosis
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    1 / 400 (0.25%)
    0 / 390 (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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 235 (0.43%)
    3 / 387 (0.78%)
    5 / 400 (1.25%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Failure to thrive
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    1 / 400 (0.25%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (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
    Hyperammonaemia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    0 / 390 (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
    Hyperglycaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Hyperglycaemic hyperosmolar nonketotic syndrome
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Hyperkalaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    0 / 387 (0.00%)
    3 / 400 (0.75%)
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Hypoglycaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    0 / 390 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 387 (0.26%)
    0 / 400 (0.00%)
    1 / 390 (0.26%)
         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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MK-3415 MK-3415A Placebo MK-6072
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    84 / 235 (35.74%)
    110 / 387 (28.42%)
    103 / 400 (25.75%)
    116 / 390 (29.74%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    15 / 235 (6.38%)
    22 / 387 (5.68%)
    14 / 400 (3.50%)
    20 / 390 (5.13%)
         occurrences all number
    19
    23
    18
    23
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    12 / 235 (5.11%)
    14 / 387 (3.62%)
    5 / 400 (1.25%)
    7 / 390 (1.79%)
         occurrences all number
    13
    15
    5
    7
    Pyrexia
         subjects affected / exposed
    14 / 235 (5.96%)
    13 / 387 (3.36%)
    15 / 400 (3.75%)
    23 / 390 (5.90%)
         occurrences all number
    18
    16
    16
    26
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    14 / 235 (5.96%)
    20 / 387 (5.17%)
    24 / 400 (6.00%)
    25 / 390 (6.41%)
         occurrences all number
    15
    21
    28
    32
    Diarrhoea
         subjects affected / exposed
    18 / 235 (7.66%)
    33 / 387 (8.53%)
    27 / 400 (6.75%)
    25 / 390 (6.41%)
         occurrences all number
    23
    38
    42
    33
    Nausea
         subjects affected / exposed
    30 / 235 (12.77%)
    33 / 387 (8.53%)
    30 / 400 (7.50%)
    32 / 390 (8.21%)
         occurrences all number
    33
    40
    35
    38
    Vomiting
         subjects affected / exposed
    11 / 235 (4.68%)
    15 / 387 (3.88%)
    16 / 400 (4.00%)
    23 / 390 (5.90%)
         occurrences all number
    13
    18
    16
    29
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    15 / 235 (6.38%)
    15 / 387 (3.88%)
    20 / 400 (5.00%)
    18 / 390 (4.62%)
         occurrences all number
    15
    15
    21
    18

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Nov 2010
    Amendment No. 01 was finalized and approved before any participants were enrolled into the study. Major changes included: updates to the statistical analysis plan; modifications to the study procedures; changes to criteria for standard of care antibiotic switching; and changes to the criteria for when to conduct an unscheduled visit.
    05 Jul 2011
    Amendment No. 02 was finalized and approved before any participants were enrolled into the study. Major changes included: addition of fidaxomicin as an allowed standard of care antibiotic; revised eligibility criteria to (1) allow initiation of standard of care therapy within a few hours after the study medication infusion, (2) exclude participants with a condition such that they routinely pass loose stool, (3) exclude participants for whom treatment with standard of care therapy was planned for longer than 14 days; removed collection of several biological samples which had been intended for exploratory analyses; reduced study medication infusion duration from 2 hours to 1 hour; updated the statistical analysis plan to address regulatory agency advice.
    20 May 2013
    Amendment No.03 was implemented after enrollment of subjects had commenced and before database lock and unblinding. Major changes included: increased infusion set filter pore size to 5 micron or smaller from 0.2 microns or smaller; removed the 9-month extended follow-up portion of the study (no participants had been enrolled in the extension prior to this amendment); updated eligibility criteria to exclude participants who had received an experimental C. difficile vaccine or other experimental monoclonal antibody against C. difficile toxin A or B, or participants who planned to receive during the follow-up period fecal transplantation therapy or any other therapies that had been demonstrated to decrease CDI recurrence; modified the definition of the clinical cure endpoint with regard to the duration of standard of care medication: a 14 day regimen was defined as treatment spanning no more than 16 calendar days.

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

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