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    Clinical Trial Results:
    A Phase III, Randomized, Open-Label, Comparative, Multi-Center Study to Assess the Safety and Efficacy of Prograf® (tacrolimus)/MMF, Modified Release (MR) Tacrolimus/MMF and Neoral® (cyclosporine)/MMF in De Novo Kidney Transplant Recipients

    Summary
    EudraCT number
    		 2015-003288-12
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    12 Mar 2009

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 May 2016
    First version publication date
    11 May 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    02-0-158
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00064701
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Astellas Pharma Global Development, Inc.
    Sponsor organisation address
    Three Parkway North, Deerfield, Illinois, United States, 60015
    Public contact
    Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., Astellas.resultsdisclosure@astellas.com
    Scientific contact
    Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., Astellas.resultsdisclosure@astellas.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Mar 2009
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Mar 2009
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to compare the safety and efficacy of Prograf/MMF and Neoral/MMF in de novo kidney transplant recipients, and to compare the safety and efficacy of MR4/MMF and Neoral/MMF in de novo kidney transplant recipients.
    Protection of trial subjects
    This clinical study was written, conducted and reported in accordance with the protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Good Clinical Practice (GCP) Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.
    Background therapy
    		 All participants were to have received mycophenolate mofetil (MMF) and corticosteroids concomitantly with the randomized study drug. Additionally, all participants were to have received induction therapy (basiliximab). Antibody induction with basiliximab 20 mg was administered intravenously on day 0 (first dose could have been administered before skin closure), a second dose was to have been administered between days 3 to 5. Corticosteroid administration was to be initiated on day 0 (500-1000 mg methylprednisolone intravenous bolus or equivalent dose) with oral administration of 200 mg methylprednisolone (or equivalent) on day 1 and subsequent tapering to achieve a targeted mean prednisone equivalent after the first 3 months of 5 to 10 mg/day.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Jun 2003
    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
    Brazil: 92
    Country: Number of subjects enrolled
    Canada: 28
    Country: Number of subjects enrolled
    United States: 548
    Worldwide total number of subjects
    668
    EEA total number of subjects
    0
    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)
    3
    Adults (18-64 years)
    594
    From 65 to 84 years
    71
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This was a 3 arm randomized, open-label, comparative, multi-center study in de novo kidney transplant recipients at 60 centers in the U.S., Canada and Brazil. De novo kidney transplant recipients 12 years of age and older were randomized in a 1:1:1 ratio to 1 of 3 treatment arms.

    Pre-assignment
    Screening details
    		 The study consisted of a 1-year post-transplant efficacy and safety study with a clinical continuation phase of a minimum of 2 years or until commercial availability of tacrolimus modified release, unless the Data Safety Monitoring Board or sponsor specified otherwise. The sponsor discontinued the study in March 2009.

    Period 1
    Period 1 title
    One year post-transplant
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    This was an open label study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tacrolimus
    Arm description
    		 Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tacrolimus
    Investigational medicinal product code
    FK506
    Other name
    Prograf
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events within a target whole blood tacrolimus trough level range of 7 to 16 ng/mL for the first 90 days post-transplant and 5 to 15 ng/mL thereafter. Participants unable to take the first dose of study drug orally or via a nasogastric tube within 48 hours following completion of the transplant procedure were discontinued from the study.

    Investigational medicinal product name
    Mycophenolate Mofetil
    Investigational medicinal product code
    Other name
    CellCept, MMF
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of Mycophenolate Mofetil (MMF) was to be administered orally or intravenously prior to, or within 48 hours of, completion of the transplant procedure. Subsequent MMF was administered in 2 equal oral doses 12 hours apart (1 g); MMF up to 1.5 g twice daily was permitted in African American/black participants. Dose-equivalent 3 or 4 times daily was permitted at the investigator’s discretion if clinically indicated. Dose changes for adverse events were permitted at the investigator’s discretion if clinically indicated.

    Arm title
    		 Tacrolimus Modified Release (MR)
    Arm description
    		 Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Tacrolimus Modified Release (MR)
    Investigational medicinal product code
    FK506
    Other name
    Advagraf, FKMR, MR4, Astagraf XL
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a first dose of tacrolimus modified release (MR4) between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events within a target whole blood tacrolimus trough level range of 7 to 16 ng/mL for the first 90 days post-transplant and 5 to 15 ng/mL thereafter. Participants unable to take the first dose of study drug orally or via a nasogastric tube within 48 hours following completion of the transplant procedure were discontinued from the study.

    Investigational medicinal product name
    Mycophenolate Mofetil
    Investigational medicinal product code
    Other name
    CellCept, MMF
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of Mycophenolate Mofetil (MMF) was to be administered orally or intravenously prior to, or within 48 hours of, completion of the transplant procedure. Subsequent MMF was administered in 2 equal oral doses 12 hours apart (1 g); MMF up to 1.5 g twice daily was permitted in African American/black participants. Dose-equivalent 3 or 4 times daily was permitted at the investigator’s discretion if clinically indicated. Dose changes for adverse events were permitted at the investigator’s discretion if clinically indicated.

    Arm title
    		 Cyclosporine
    Arm description
    		 Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Cyclosporine
    Investigational medicinal product code
    Other name
    Cyclosporine, Neoral, CsA
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events within a target whole blood trough level range of 125 to 400 ng/mL for the first 90 days post-transplant and 100 to 300 ng/mL thereafter. Participants unable to take the first dose of study drug orally or via a nasogastric tube within 48 hours following completion of the transplant procedure were discontinued from the study.

    Investigational medicinal product name
    Mycophenolate Mofetil
    Investigational medicinal product code
    Other name
    CellCept, MMF
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of Mycophenolate Mofetil (MMF) was to be administered orally or intravenously prior to, or within 48 hours of, completion of the transplant procedure. Subsequent MMF was administered in 2 equal oral doses 12 hours apart (1 g); MMF up to 1.5 g twice daily was permitted in African American/black participants. Dose-equivalent 3 or 4 times daily was permitted at the investigator’s discretion if clinically indicated. Dose changes for adverse events were permitted at the investigator’s discretion if clinically indicated.

    Number of subjects in period 1
    		Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Started
    219
    226
    223
    Received Study Drug
    212
    214
    212
    Completed
    212
    214
    212
    Not completed
    7
    12
    11
         Did not receive study drug
    7
    12
    11
    Period 2
    Period 2 title
    Full Analysis Set (FAS) for baseline
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    This was an open label study. The FAS was defined as all randomized participants who received at least one dose of study drug, was part of the one year post-transplant period and was only added here for baseline characteristics reporting purposes.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tacrolimus
    Arm description
    		 Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tacrolimus
    Investigational medicinal product code
    FK506
    Other name
    Prograf
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events within a target whole blood tacrolimus trough level range of 7 to 16 ng/mL for the first 90 days post-transplant and 5 to 15 ng/mL thereafter. Participants unable to take the first dose of study drug orally or via a nasogastric tube within 48 hours following completion of the transplant procedure were discontinued from the study.

    Investigational medicinal product name
    Mycophenolate Mofetil
    Investigational medicinal product code
    Other name
    CellCept, MMF
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of Mycophenolate Mofetil (MMF) was to be administered orally or intravenously prior to, or within 48 hours of, completion of the transplant procedure. Subsequent MMF was administered in 2 equal oral doses 12 hours apart (1 g); MMF up to 1.5 g twice daily was permitted in African American/black participants. Dose-equivalent 3 or 4 times daily was permitted at the investigator’s discretion if clinically indicated. Dose changes for adverse events were permitted at the investigator’s discretion if clinically indicated.

    Arm title
    		 Tacrolimus Modified Release (MR)
    Arm description
    		 Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Tacrolimus Modified Release (MR)
    Investigational medicinal product code
    FK506
    Other name
    Advagraf, FKMR, MR4, Astagraf XL
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a first dose of tacrolimus modified release (MR4) between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events within a target whole blood tacrolimus trough level range of 7 to 16 ng/mL for the first 90 days post-transplant and 5 to 15 ng/mL thereafter. Participants unable to take the first dose of study drug orally or via a nasogastric tube within 48 hours following completion of the transplant procedure were discontinued from the study.

    Investigational medicinal product name
    Mycophenolate Mofetil
    Investigational medicinal product code
    Other name
    CellCept, MMF
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of Mycophenolate Mofetil (MMF) was to be administered orally or intravenously prior to, or within 48 hours of, completion of the transplant procedure. Subsequent MMF was administered in 2 equal oral doses 12 hours apart (1 g); MMF up to 1.5 g twice daily was permitted in African American/black participants. Dose-equivalent 3 or 4 times daily was permitted at the investigator’s discretion if clinically indicated. Dose changes for adverse events were permitted at the investigator’s discretion if clinically indicated.

    Arm title
    		 Cyclosporine
    Arm description
    		 Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Cyclosporine
    Investigational medicinal product code
    Other name
    Cyclosporine, Neoral, CsA
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events within a target whole blood trough level range of 125 to 400 ng/mL for the first 90 days post-transplant and 100 to 300 ng/mL thereafter. Participants unable to take the first dose of study drug orally or via a nasogastric tube within 48 hours following completion of the transplant procedure were discontinued from the study.

    Investigational medicinal product name
    Mycophenolate Mofetil
    Investigational medicinal product code
    Other name
    CellCept, MMF
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of Mycophenolate Mofetil (MMF) was to be administered orally or intravenously prior to, or within 48 hours of, completion of the transplant procedure. Subsequent MMF was administered in 2 equal oral doses 12 hours apart (1 g); MMF up to 1.5 g twice daily was permitted in African American/black participants. Dose-equivalent 3 or 4 times daily was permitted at the investigator’s discretion if clinically indicated. Dose changes for adverse events were permitted at the investigator’s discretion if clinically indicated.

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: The baseline period includes participants included in the full analysis set (only participants that were randomized and received at least one dose of study drug).
    Number of subjects in period 2 [2]
    		Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Started
    212
    214
    212
    Completed
    179
    183
    151
    Not completed
    33
    31
    61
         Graft failure
    3
    2
    1
         Converted to rapamycin
    1
    -
    -
         Adverse event, non-fatal
    23
    19
    37
         Rejection
    -
    1
    16
         Incorrect study drug dispensed
    -
    1
    -
         Poor absorption
    -
    1
    -
         Non-compliance
    4
    2
    5
         Lost to follow-up
    1
    -
    -
         Acute tubular necrosis
    1
    -
    -
         Crossover secondary to possible toxicity
    -
    1
    -
         Pancreas transplant
    -
    -
    1
         Withdrawal by subject
    -
    4
    1
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The worldwide number enrolled in the trial includes all randomized participants. The baseline period includes participants included in the full analysis set (only participants that were randomized and received at least one dose of study drug).
    Period 3
    Period 3 title
    Clinical Continuation Phase
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    This was an open label study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tacrolimus
    Arm description
    		 Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tacrolimus
    Investigational medicinal product code
    FK506
    Other name
    Prograf
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events within a target whole blood tacrolimus trough level range of 7 to 16 ng/mL for the first 90 days post-transplant and 5 to 15 ng/mL thereafter. Participants unable to take the first dose of study drug orally or via a nasogastric tube within 48 hours following completion of the transplant procedure were discontinued from the study.

    Investigational medicinal product name
    Mycophenolate Mofetil
    Investigational medicinal product code
    Other name
    CellCept, MMF
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of Mycophenolate Mofetil (MMF) was to be administered orally or intravenously prior to, or within 48 hours of, completion of the transplant procedure. Subsequent MMF was administered in 2 equal oral doses 12 hours apart (1 g); MMF up to 1.5 g twice daily was permitted in African American/black participants. Dose-equivalent 3 or 4 times daily was permitted at the investigator’s discretion if clinically indicated. Dose changes for adverse events were permitted at the investigator’s discretion if clinically indicated.

    Arm title
    		 Tacrolimus Modified Release (MR)
    Arm description
    		 Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Tacrolimus Modified Release (MR)
    Investigational medicinal product code
    FK506
    Other name
    Advagraf, FKMR, MR4, Astagraf XL
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a first dose of tacrolimus modified release (MR4) between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events within a target whole blood tacrolimus trough level range of 7 to 16 ng/mL for the first 90 days post-transplant and 5 to 15 ng/mL thereafter. Participants unable to take the first dose of study drug orally or via a nasogastric tube within 48 hours following completion of the transplant procedure were discontinued from the study.

    Investigational medicinal product name
    Mycophenolate Mofetil
    Investigational medicinal product code
    Other name
    CellCept, MMF
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of Mycophenolate Mofetil (MMF) was to be administered orally or intravenously prior to, or within 48 hours of, completion of the transplant procedure. Subsequent MMF was administered in 2 equal oral doses 12 hours apart (1 g); MMF up to 1.5 g twice daily was permitted in African American/black participants. Dose-equivalent 3 or 4 times daily was permitted at the investigator’s discretion if clinically indicated. Dose changes for adverse events were permitted at the investigator’s discretion if clinically indicated.

    Arm title
    		 Cyclosporine
    Arm description
    		 Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Cyclosporine
    Investigational medicinal product code
    Other name
    Cyclosporine, Neoral, CsA
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events within a target whole blood trough level range of 125 to 400 ng/mL for the first 90 days post-transplant and 100 to 300 ng/mL thereafter. Participants unable to take the first dose of study drug orally or via a nasogastric tube within 48 hours following completion of the transplant procedure were discontinued from the study.

    Investigational medicinal product name
    Mycophenolate Mofetil
    Investigational medicinal product code
    Other name
    CellCept, MMF
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The first dose of Mycophenolate Mofetil (MMF) was to be administered orally or intravenously prior to, or within 48 hours of, completion of the transplant procedure. Subsequent MMF was administered in 2 equal oral doses 12 hours apart (1 g); MMF up to 1.5 g twice daily was permitted in African American/black participants. Dose-equivalent 3 or 4 times daily was permitted at the investigator’s discretion if clinically indicated. Dose changes for adverse events were permitted at the investigator’s discretion if clinically indicated.

    Number of subjects in period 3 [3]
    		Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Started
    179
    182
    151
    Completed
    9
    4
    11
    Not completed
    170
    178
    140
         Physician decision
    1
    3
    -
         Discharged to nursing home
    -
    1
    -
         Rejection
    1
    2
    2
         Unable to return to site for study visit
    1
    -
    1
         Incorrect study drug dispensed
    -
    1
    -
         Sponsor discontinued study
    113
    129
    79
         Patient opted out
    -
    -
    1
         Immunosuppressive treatment crossover
    -
    3
    6
         Ran out of study drug due to Hurricane
    -
    1
    -
         Withdrawal by subject
    22
    3
    22
         Graft failure
    5
    5
    2
         Adverse event, non-fatal
    12
    21
    14
         Non-compliance
    8
    6
    7
         Lost to follow-up
    6
    3
    6
         Pancreas transplant
    1
    -
    -
    Notes
    [3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: One participant from Arm 2 (Tacrolimus Modified Release) did not enter the Clinical Continuation phase.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Tacrolimus
    Reporting group description
    		 Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group title
    Tacrolimus Modified Release (MR)
    Reporting group description
    		 Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group title
    Cyclosporine
    Reporting group description
    		 Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine Total
    Number of subjects
    		 212 214 212
    Age categorical
    Units: Subjects
    Age continuous
    Baseline characteristics provided for the full analysis set (FAS), defined as all randomized participants who received at least one dose of study drug.
    Units: years
        arithmetic mean (standard deviation)
    		 48.62 ± 12.855 47.84 ± 12.995 47.63 ± 12.953 -
    Gender categorical
    Gender categorical description
    Units: Subjects
        Female
    		 76 76 82 234
        Male
    		 136 138 130 404
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 152 160 163 475
        Black
    		 51 41 36 128
        Asian
    		 5 5 8 18
        Other
    		 4 8 5 17
    Primary Diagnosis
    Units: Subjects
        Nephrosclerosis/ Hypertensive Nephropathy
    		 54 56 43 153
        Diabetic Nephropathy
    		 46 38 46 130
        Glomerulonephritis
    		 44 43 43 130
        Polycycstic Kidney Disease
    		 20 26 20 66
        Tubular/ Interstitial Disease
    		 9 5 16 30
        Systemic Vasculitis
    		 9 10 7 26
        Congenital/ Hereditary Nephropathy
    		 7 7 13 27
        Reflux
    		 1 0 1 2
        Unknown
    		 17 24 17 58
        Other
    		 5 5 6 16
    Previous Transplant
    Units: Subjects
        No
    		 205 206 203 614
        Yes
    		 7 8 9 24

    End points

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    End points reporting groups
    Reporting group title
    Tacrolimus
    Reporting group description
    		 Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group title
    Tacrolimus Modified Release (MR)
    Reporting group description
    		 Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group title
    Cyclosporine
    Reporting group description
    		 Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Reporting group title
    Tacrolimus
    Reporting group description
    		 Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group title
    Tacrolimus Modified Release (MR)
    Reporting group description
    		 Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group title
    Cyclosporine
    Reporting group description
    		 Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
    Reporting group title
    Tacrolimus
    Reporting group description
    		 Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group title
    Tacrolimus Modified Release (MR)
    Reporting group description
    		 Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group title
    Cyclosporine
    Reporting group description
    		 Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Primary: Percentage of participants with Efficacy Failure

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    End point title
    		 Percentage of participants with Efficacy Failure
    End point description
    Efficacy failure is defined as any participant who died, experienced a graft failure (permanent return to dialysis [> 30 days] or retransplant), had a biopsy-confirmed (Banff Grade ≥ I) acute rejection (BCAR), or was lost to follow-up. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. The number of participants analyzed represents the full analysis set (FAS), defined as all randomized patients who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    One year
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: percentage of participants
        number (not applicable)
    15.1
    14
    17
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The non-inferiority margin for the difference between treatment groups (Tacrolimus minus Cyclosporine) was pre-specified as 10%. If the lower limit of the confidence interval was greater than -10%, then Tacrolimus was considered non-inferior to Cyclosporine.
    Comparison groups
    Cyclosporine v Tacrolimus
    Number of subjects included in analysis
    424
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Incidence Difference
    Point estimate
    -1.9
    Confidence interval
         level
    		 95.2%
         sides
    2-sided
         lower limit
    		 -8.9
         upper limit
    		 5.2
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The non-inferiority margin for the difference between treatment groups (Tacrolimus MR minus Cyclosporine) was pre-specified as 10%. If the lower limit of the confidence interval was greater than -10%, then Tacrolimus MR was considered non-inferior to Cyclosporine.
    Comparison groups
    Cyclosporine v Tacrolimus Modified Release (MR)
    Number of subjects included in analysis
    426
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Incidence Difference
    Point estimate
    -3
    Confidence interval
         level
    		 95.2%
         sides
    2-sided
         lower limit
    		 -9.9
         upper limit
    		 4

    Secondary: Patient Survival at one year

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    End point title
    		 Patient Survival at one year
    End point description
    Patient survival is defined as any participant who is known to be alive one year after the skin closure date. Participants who died or whose outcome was unknown at one year were considered to be non-survivors. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    One year
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: percentage of participants
        number (not applicable)
    93.9
    97.2
    97.2
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The difference in survival rates was calculated as Tacrolimus minus Cyclosporine.
    Comparison groups
    Tacrolimus v Cyclosporine
    Number of subjects included in analysis
    424
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Incidence Difference
    Point estimate
    -3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.2
         upper limit
    		 0.6
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The difference in survival rates was calculated as Tacrolimus MR minus Cyclosporine.
    Comparison groups
    Cyclosporine v Tacrolimus Modified Release (MR)
    Number of subjects included in analysis
    426
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    Method
    Parameter type
    		 Incidence Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 3.2
    Notes
    [1] - The non-inferiority margin for this study was pre-specified as 10%.

    Secondary: Graft Survival at one year

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    End point title
    		 Graft Survival at one year
    End point description
    Graft survival defined as any participant who did not meet the criteria for graft loss, where graft loss is defined as any re-transplant, permanent return to dialysis (> 30 days), patient death, or participant whose outcome at one year was unknown. Participants were only counted once regardless of how many criteria were met. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    One year
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: percentage of participants
        number (not applicable)
    91.5
    95.3
    95.3
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The difference in survival rates was calculated as Tacrolimus minus Cyclosporine.
    Comparison groups
    Cyclosporine v Tacrolimus
    Number of subjects included in analysis
    424
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Incidence Difference
    Point estimate
    -3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.5
         upper limit
    		 0.9
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The difference in survival rates was calculated as Tacrolimus MR minus Cyclosporine.
    Comparison groups
    Cyclosporine v Tacrolimus Modified Release (MR)
    Number of subjects included in analysis
    426
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Incidence Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 4.1

    Secondary: Percentage of participants with biopsy confirmed acute rejection at 6 and 12 months

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    End point title
    		 Percentage of participants with biopsy confirmed acute rejection at 6 and 12 months
    End point description
    Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. Acute rejection is defined as a grade ≥ I. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    Six months and 12 months
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: percentage of participants
    number (not applicable)
        At 6 Months
    3.8
    7.9
    11.8
        At 12 Months
    7.5
    10.3
    13.7
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Comparison of tacrolimus with cyclosporine at 6 months. The difference in biopsy confirmed acute rejection rates was calculated as Tacrolimus minus Cyclosporine.
    Comparison groups
    Tacrolimus v Cyclosporine
    Number of subjects included in analysis
    424
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Incidence Difference at 6 Months
    Point estimate
    -8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.1
         upper limit
    		 -3
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Comparison of Tacrolimus Modified Release with Cyclosporine at 6 months. The difference in biopsy confirmed acute rejection rates was calculated as Tacrolimus MR minus Cyclosporine.
    Comparison groups
    Tacrolimus Modified Release (MR) v Cyclosporine
    Number of subjects included in analysis
    426
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Incidence Difference at 6 Months
    Point estimate
    -3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.5
         upper limit
    		 1.8
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Comparison of tacrolimus with cyclosporine at 12 months. The difference in biopsy confirmed acute rejection rates was calculated as Tacrolimus minus Cyclosporine.
    Comparison groups
    Tacrolimus v Cyclosporine
    Number of subjects included in analysis
    424
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Incidence Difference at 12 Months
    Point estimate
    -6.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12
         upper limit
    		 -0.3
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Comparison of Tacrolimus Modified Release with Cyclosporine at 12 months. The difference in biopsy confirmed acute rejection rates was calculated as Tacrolimus MR minus Cyclosporine.
    Comparison groups
    Tacrolimus Modified Release (MR) v Cyclosporine
    Number of subjects included in analysis
    426
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Incidence Difference at 12 months
    Point estimate
    -3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.6
         upper limit
    		 2.8

    Secondary: Time to first biopsy-confirmed acute rejection episode

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    End point title
    		 Time to first biopsy-confirmed acute rejection episode
    End point description
    Time to first biopsy-confirmed acute rejection episode defined as the number of days from skin closure (Day 0) to the date of biopsy. Rejection episodes were confirmed by biopsy by the clinical site pathologist and graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. Acute rejection is defined as a grade ≥ I. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    One year
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: days
        median (full range (min-max))
    156 (3 to 316)
    11 (6 to 327)
    52 (1 to 311)
    No statistical analyses for this end point

    Secondary: Number of participants requiring anti-lymphocyte antibody therapy for treatment of rejection

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    End point title
    		 Number of participants requiring anti-lymphocyte antibody therapy for treatment of rejection
    End point description
    Rejection episodes were confirmed by biopsy by the clinical site pathologist. Participants with histologically-proven Banff Grade II or III rejection or participants with steroid-resistant rejection were treated with anti-lymphocyte antibody treatment according to institutional practice. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    One year
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: participants
    6
    8
    18
    No statistical analyses for this end point

    Secondary: Severity of acute rejection

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    End point title
    		 Severity of acute rejection
    End point description
    Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade IA: Significant interstitial infiltration and foci of moderate tubulitis; Grade IB: Significant interstitial infiltration and foci of severe tubulitis; Grade IIA: Mild to moderate intimal arteritis in at least 1 arterial cross section; Grade IIB: Severe intimal arteritis comprising >25% of the luminal area lost in at least 1 arterial cross section; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. The number of participants analyzed represents the FAS with a biopsy-confirmed acute rejection episode during one year.
    End point type
    Secondary
    End point timeframe
    One year
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    16
    22
    29
    Units: participants
        Grade I-A
    8
    11
    14
        Grade I-B
    4
    3
    6
        Grade II-A
    3
    6
    6
        Grade II-B
    1
    1
    1
        Grade III
    0
    1
    2
    No statistical analyses for this end point

    Secondary: Number of participants experiencing multiple rejection episodes

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    End point title
    		 Number of participants experiencing multiple rejection episodes
    End point description
    This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    One year
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: participants
    2
    4
    8
    No statistical analyses for this end point

    Secondary: Number of participants with clinically treated acute rejection episodes

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    End point title
    		 Number of participants with clinically treated acute rejection episodes
    End point description
    A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    One year
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: participants
    25
    39
    45
    No statistical analyses for this end point

    Secondary: Number of participants with Treatment failure

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    End point title
    		 Number of participants with Treatment failure
    End point description
    Treatment failure was defined as the discontinuation of randomized study drug for any reason. Participants who met the definition of treatment failure were to be followed throughout the 12-month treatment period. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    One year
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: participants
    33
    31
    61
    No statistical analyses for this end point

    Secondary: Number of participants who crossed over due to treatment failure

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    End point title
    		 Number of participants who crossed over due to treatment failure
    End point description
    Participants were allowed to cross over to an alternative primary immunosuppressive regimen (either to the tacrolimus or cyclosporine treatment arms) to address an adverse event which led to randomized study drug discontinuation or in the case of severe or refractory rejection. Crossover to the modified release tacrolimus treatment arm was not permitted. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    One year
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: participants
    6
    10
    39
    No statistical analyses for this end point

    Secondary: Change from Month 1 in Serum Creatinine at Month 6 and Month 12

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    End point title
    		 Change from Month 1 in Serum Creatinine at Month 6 and Month 12
    End point description
    Renal function was assessed by the change from Month 1 in serum creatinine six months and 12 months after transplant. The number (N) of participants analyzed represents the FAS with available data at Month 1 and at each time point.
    End point type
    Secondary
    End point timeframe
    Month 1, Month 6, and Month 12
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: mg/dL
    arithmetic mean (standard deviation)
        At 6 months [N=184, 184, 169]
    -0.09 ± 0.63
    -0.08 ± 0.56
    -0.01 ± 0.53
        At 12 months [N=173, 182, 147]
    -0.08 ± 0.76
    -0.14 ± 0.62
    -0.04 ± 0.53
    No statistical analyses for this end point

    Secondary: Change from Month 1 in Creatinine Clearance at Month 6 and Month 12

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    End point title
    		 Change from Month 1 in Creatinine Clearance at Month 6 and Month 12
    End point description
    Renal function was assessed by creatinine clearance, calculated using the Cockcroft-Gault formula. The number (N) of participants analyzed represents the FAS with available data at Month 1 and at each time point.
    End point type
    Secondary
    End point timeframe
    Month 1, Month 6, and Month 12
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: mL/min
    arithmetic mean (standard deviation)
        At 6 months [N=184, 184, 167]
    0.83 ± 13.77
    0.47 ± 12.9
    -1.79 ± 14.09
        At 12 months [N=173, 182, 145]
    1.5 ± 16.07
    2.62 ± 14.32
    -0.25 ± 14.54
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Patient Survival at the end of the study

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    End point title
    		 Kaplan-Meier Estimate of Patient Survival at the end of the study
    End point description
    Patient survival was defined as any participant who was alive at the end of the study. Patient survival was censored at the time of last follow-up contact. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    End of study (maximum time on study was 1,941 days)
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: percentage of participants
        number (confidence interval 95%)
    91.2 (86.8 to 95.7)
    93.2 (89.7 to 96.8)
    91.7 (87.7 to 95.8)
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Tacrolimus v Cyclosporine
    Number of subjects included in analysis
    424
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.5
         upper limit
    		 5.5
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Tacrolimus Modified Release (MR) v Cyclosporine
    Number of subjects included in analysis
    426
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.9
         upper limit
    		 6.9

    Secondary: Kaplan-Meier Estimate of Graft Survival at the end of the study

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    End point title
    		 Kaplan-Meier Estimate of Graft Survival at the end of the study
    End point description
    Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was any retransplant or the permanent return to dialysis (more than 30 days) or patient death. Graft survival was censored at the time of last follow-up contact. The number of participants analyzed represents the FAS.
    End point type
    Secondary
    End point timeframe
    End of study (maximum time on study was 1,941 days)
    End point values
    		 Tacrolimus Tacrolimus Modified Release (MR) Cyclosporine
    Number of subjects analysed
    212
    214
    212
    Units: percentage of participants
        number (confidence interval 95%)
    82.7 (76.9 to 88.4)
    84.7 (79 to 90.4)
    83.9 (78.6 to 89.3)
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Cyclosporine v Tacrolimus
    Number of subjects included in analysis
    424
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.1
         upper limit
    		 6.6
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Tacrolimus Modified Release (MR) v Cyclosporine
    Number of subjects included in analysis
    426
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.1
         upper limit
    		 8.6

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 1941 days
    Adverse event reporting additional description
    An adverse event (AE) was defined as any reaction, side effect, or other untoward medical occurrence, regardless of the relationship to study drug, which occurred during the conduct of the study. Clinically significant adverse changes in clinical status, ECGs, routine labs, x-rays, physical examinations, etc., were considered adverse events.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    6.1
    Reporting groups
    Reporting group title
    Tacrolimus
    Reporting group description
    		 Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group title
    Cyclosporine
    Reporting group description
    		 Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Reporting group title
    Tacrolimus Modified Release
    Reporting group description
    		 Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.

    Serious adverse events
    		 Tacrolimus Cyclosporine Tacrolimus Modified Release
    Total subjects affected by serious adverse events
         subjects affected / exposed
    148 / 212 (69.81%)
    139 / 212 (65.57%)
    141 / 214 (65.89%)
         number of deaths (all causes)
    13
    9
    9
         number of deaths resulting from adverse events
    5
    1
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenoma benign
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carcinoid tumour of the appendix
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carcinoid tumour of the pancreas
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carcinoid tumour of the stomach
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Kaposi's sarcoma
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphoroliferative disorder
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastatic renal cell carcinoma
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    3 / 212 (1.42%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma stage unspecified
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    4 / 212 (1.89%)
    2 / 212 (0.94%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    6 / 6
    2 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine cancer
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arterial stenosis limb
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arterial thrombosis limb
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous fistula, acquired
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atherosclerosis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    7 / 212 (3.30%)
    4 / 212 (1.89%)
    4 / 214 (1.87%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral arterial stenosis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral artery occlusion
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    1 / 212 (0.47%)
    2 / 212 (0.94%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    2 / 212 (0.94%)
    2 / 212 (0.94%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 212 (0.00%)
    3 / 212 (1.42%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    2 / 212 (0.94%)
    2 / 212 (0.94%)
    5 / 214 (2.34%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iliac artery stenosis
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intermittent Claudication
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    2 / 212 (0.94%)
    4 / 212 (1.89%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphorrhoea
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery dissection
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral occlusive disease
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renovascular Hypertension
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular Insufficiency
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Venous stenosis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Abdominal hernia repair
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal panniculectomy
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominoplasty
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystectomy
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colostomy closure
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary arterial stent insertion
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip arthroplasty
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hospitalisation
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia repair
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Knee arthroplasty
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrectomy
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreas transplant
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parathyroidectomy
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal resection
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia repair
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adhesion
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anasarca
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Catheter site haemorrhage
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    4 / 214 (1.87%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 212 (2.36%)
    8 / 212 (3.77%)
    5 / 214 (2.34%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 9
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rigors
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Swelling
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulcer haemorrhage
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Graft loss
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Kidney transplant rejection
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    Murder
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Treatment noncompliance
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endometriosis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erectile dysfunction
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gynaecomastia
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst torsion
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic muscles inadequate
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Priapism
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Scrotal oedema
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Testicular infarction
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterovaginal prolapse
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory failure
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic Obstructive airways Disease
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic Obstructive airways Disease exacerbated
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 212 (0.94%)
    2 / 212 (0.94%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exacerbated
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal oedema
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Maxillary sinusitis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    6 / 212 (2.83%)
    3 / 212 (1.42%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Restrictive pulmonary disease
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Completed Suicide
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    3 / 212 (1.42%)
    0 / 212 (0.00%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary dilatation
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 212 (0.47%)
    2 / 212 (0.94%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic lesion
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatine increased
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    18 / 212 (8.49%)
    15 / 212 (7.08%)
    11 / 214 (5.14%)
         occurrences causally related to treatment / all
    15 / 26
    8 / 16
    4 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood glucose increased
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood in stool
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac stress test abnormal
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus test positive
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematocrit decreased
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urine output decreased
         subjects affected / exposed
    0 / 212 (0.00%)
    3 / 212 (1.42%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Volume blood decreased
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous graft site complication
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous graft thrombosis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Burns third degree
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac pacemaker malfunction
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Complications of transplant surgery
         subjects affected / exposed
    5 / 212 (2.36%)
    2 / 212 (0.94%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    2 / 6
    1 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug toxicity
         subjects affected / exposed
    1 / 212 (0.47%)
    2 / 212 (0.94%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot Fracture
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Graft complication
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Graft dysfunction
         subjects affected / exposed
    5 / 212 (2.36%)
    2 / 212 (0.94%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    3 / 5
    2 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria traumatic
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incision site complication
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incision site haemorrhage
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    2 / 212 (0.94%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Medical device complication
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meniscus lesion
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Perinephric collection
         subjects affected / exposed
    1 / 212 (0.47%)
    2 / 212 (0.94%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Perirenal haematoma
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural discharge
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural pain
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural urine leak
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative haematoma
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pubic rami fracture
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal haematoma
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal injury
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Therapeutic agent toxicity
         subjects affected / exposed
    5 / 212 (2.36%)
    1 / 212 (0.47%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    5 / 5
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic haematoma
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound secretion
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Anomalous pulmonary venous connection
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital cystic kidney disease
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Angina pectoris
         subjects affected / exposed
    3 / 212 (1.42%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 212 (0.94%)
    3 / 212 (1.42%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Atrial flutter
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    3 / 212 (1.42%)
    2 / 212 (0.94%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    1 / 3
    0 / 2
    0 / 1
    Cardiac failure
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    3 / 212 (1.42%)
    1 / 212 (0.47%)
    6 / 214 (2.80%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    Cardiogenic shock
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    4 / 212 (1.89%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    5 / 212 (2.36%)
    4 / 212 (1.89%)
    4 / 214 (1.87%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular bigeminy
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebellar haemorrhage
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Convulsion
         subjects affected / exposed
    3 / 212 (1.42%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic hyperosmolar coma
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysaesthesia
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Guillain Barre syndrome
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple sclerosis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuropathy
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sleep paralysis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viith nerve paralysis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 212 (2.83%)
    5 / 212 (2.36%)
    4 / 214 (1.87%)
         occurrences causally related to treatment / all
    3 / 6
    2 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemolysis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 212 (0.47%)
    3 / 212 (1.42%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombotic microangiopathy
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinitis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal haematoma
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    5 / 212 (2.36%)
    5 / 212 (2.36%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal strangulated hernia
         subjects affected / exposed
    0 / 212 (0.00%)
    3 / 212 (1.42%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal wall cyst
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal wall disorder
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute abdomen
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    12 / 212 (5.66%)
    3 / 212 (1.42%)
    10 / 214 (4.67%)
         occurrences causally related to treatment / all
    3 / 14
    1 / 3
    3 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea haemorrhagic
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    2 / 212 (0.94%)
    1 / 212 (0.47%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    5 / 212 (2.36%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gingival hyperplasia
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 212 (0.47%)
    2 / 212 (0.94%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    7 / 212 (3.30%)
    3 / 212 (1.42%)
    6 / 214 (2.80%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 3
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal erosion
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis due to biliary obstruction
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis haemorrhagic
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritoneal haematoma
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proctalgia
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal polyp
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal ulcer
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Salivary gland enlargement
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia, obstructive
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    8 / 212 (3.77%)
    5 / 212 (2.36%)
    8 / 214 (3.74%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 5
    2 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute prerenal failure
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Azotaemia
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder disorder
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder neck obstruction
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    2 / 212 (0.94%)
    2 / 212 (0.94%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    2 / 212 (0.94%)
    4 / 212 (1.89%)
    4 / 214 (1.87%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage urinary tract
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    3 / 212 (1.42%)
    4 / 212 (1.89%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydroureter
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephropathy
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephropathy Toxic
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrotic Syndrome
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvi-ureteric obstruction
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal Impairment
         subjects affected / exposed
    4 / 212 (1.89%)
    3 / 212 (1.42%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    3 / 4
    2 / 3
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal artery stenosis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal artery thrombosis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    9 / 212 (4.25%)
    7 / 212 (3.30%)
    4 / 214 (1.87%)
         occurrences causally related to treatment / all
    3 / 11
    2 / 7
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure chronic
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal insufficiency
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    5 / 214 (2.34%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal vein thrombosis
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stress incontinence
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urethral meatus stenosis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urethral obstruction
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 212 (0.47%)
    2 / 212 (0.94%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinoma
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperparathyroidism
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperparathyroidism tertiary
         subjects affected / exposed
    3 / 212 (1.42%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 212 (0.47%)
    2 / 212 (0.94%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone Spur
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Compartment syndrome
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fracture malunion
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gouty arthritis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc space narrowing
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint swelling
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised osteoarthritis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Monoarthritis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Plantar fasciitis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spondylosis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    2 / 212 (0.94%)
    2 / 212 (0.94%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial pyelonephritis
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    3 / 212 (1.42%)
    1 / 212 (0.47%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis acute
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Catheter related infection
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Catheter sepsis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    4 / 212 (1.89%)
    4 / 212 (1.89%)
    5 / 214 (2.34%)
         occurrences causally related to treatment / all
    3 / 7
    2 / 4
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cellulitis gangrenous
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Choriomeningitis lymphocytic
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Clostridial infection
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium colitis
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Condyloma acuminatum
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus colitis
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus gastritis
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    15 / 212 (7.08%)
    11 / 212 (5.19%)
    11 / 214 (5.14%)
         occurrences causally related to treatment / all
    14 / 17
    6 / 14
    6 / 12
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Cytomegalovirus oesophagitis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus viraemia
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    1 / 212 (0.47%)
    2 / 212 (0.94%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis bacterial
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    3 / 212 (1.42%)
    5 / 212 (2.36%)
    6 / 214 (2.80%)
         occurrences causally related to treatment / all
    0 / 4
    2 / 5
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Furuncle
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis fungal
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    4 / 212 (1.89%)
    3 / 212 (1.42%)
    14 / 214 (6.54%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 4
    6 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    5 / 212 (2.36%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    3 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Groin infection
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Helicobacter gastritis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes virus infection
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    3 / 212 (1.42%)
    1 / 212 (0.47%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpetic gingivostomatitis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Human polyomavirus infection
         subjects affected / exposed
    9 / 212 (4.25%)
    1 / 212 (0.47%)
    5 / 214 (2.34%)
         occurrences causally related to treatment / all
    9 / 10
    0 / 1
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected cyst
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    4 / 214 (1.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Klebsiella bacteraemia
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung infection pseudomonal
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mastoiditis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis aseptic
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis cryptococcal
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mycobacterium avium complex infection
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    2 / 212 (0.94%)
    1 / 212 (0.47%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Papilloma viral infection
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parvovirus infection
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Perinephric abscess
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Phlebitis infective
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    4 / 212 (1.89%)
    7 / 212 (3.30%)
    10 / 214 (4.67%)
         occurrences causally related to treatment / all
    2 / 4
    3 / 11
    4 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    Pneumonia fungal
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia haemophilus
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia klebsiella
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative abscess
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative infection
         subjects affected / exposed
    0 / 212 (0.00%)
    2 / 212 (0.94%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    4 / 212 (1.89%)
    3 / 212 (1.42%)
    5 / 214 (2.34%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 3
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 212 (0.47%)
    2 / 212 (0.94%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    6 / 212 (2.83%)
    4 / 212 (1.89%)
    8 / 214 (3.74%)
         occurrences causally related to treatment / all
    5 / 6
    2 / 4
    3 / 8
         deaths causally related to treatment / all
    3 / 4
    0 / 0
    0 / 2
    Septic shock
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin bacterial infection
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal infection
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Strongyloidiasis
         subjects affected / exposed
    3 / 212 (1.42%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    15 / 212 (7.08%)
    15 / 212 (7.08%)
    11 / 214 (5.14%)
         occurrences causally related to treatment / all
    3 / 18
    4 / 17
    3 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    3 / 212 (1.42%)
    4 / 212 (1.89%)
    3 / 214 (1.40%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 4
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    2 / 212 (0.94%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection fungal
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection pseudomonal
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection staphylococcal
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    5 / 212 (2.36%)
    5 / 212 (2.36%)
    5 / 214 (2.34%)
         occurrences causally related to treatment / all
    5 / 8
    0 / 5
    5 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Vaginitis
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vancomycin-resistant enterococcal infection
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Varicella
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 212 (0.00%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vulval abscess
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    9 / 212 (4.25%)
    6 / 212 (2.83%)
    10 / 214 (4.67%)
         occurrences causally related to treatment / all
    1 / 10
    0 / 6
    1 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    2 / 212 (0.94%)
    4 / 212 (1.89%)
    6 / 214 (2.80%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 4
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    4 / 212 (1.89%)
    2 / 212 (0.94%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    3 / 4
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes with hyperosmolarity
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    4 / 214 (1.87%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    2 / 212 (0.94%)
    1 / 212 (0.47%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    5 / 212 (2.36%)
    3 / 212 (1.42%)
    5 / 214 (2.34%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 3
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    5 / 212 (2.36%)
    1 / 212 (0.47%)
    5 / 214 (2.34%)
         occurrences causally related to treatment / all
    3 / 6
    0 / 1
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 212 (0.47%)
    2 / 212 (0.94%)
    1 / 214 (0.47%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 212 (0.47%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    2 / 212 (0.94%)
    0 / 212 (0.00%)
    2 / 214 (0.93%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 212 (0.47%)
    0 / 212 (0.00%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    0 / 212 (0.00%)
    1 / 212 (0.47%)
    0 / 214 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Tacrolimus Cyclosporine Tacrolimus Modified Release
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    209 / 212 (98.58%)
    209 / 212 (98.58%)
    213 / 214 (99.53%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    63 / 212 (29.72%)
    69 / 212 (32.55%)
    59 / 214 (27.57%)
         occurrences all number
    100
    101
    92
    Hypotension
         subjects affected / exposed
    17 / 212 (8.02%)
    17 / 212 (8.02%)
    19 / 214 (8.88%)
         occurrences all number
    23
    20
    24
    Orthostatic Hypotension
         subjects affected / exposed
    9 / 212 (4.25%)
    5 / 212 (2.36%)
    15 / 214 (7.01%)
         occurrences all number
    9
    5
    15
    General disorders and administration site conditions
    Anasarca
         subjects affected / exposed
    8 / 212 (3.77%)
    4 / 212 (1.89%)
    12 / 214 (5.61%)
         occurrences all number
    8
    5
    13
    Asthenia
         subjects affected / exposed
    22 / 212 (10.38%)
    22 / 212 (10.38%)
    16 / 214 (7.48%)
         occurrences all number
    24
    24
    20
    Chest pain
         subjects affected / exposed
    16 / 212 (7.55%)
    12 / 212 (5.66%)
    19 / 214 (8.88%)
         occurrences all number
    20
    16
    19
    Fatigue
         subjects affected / exposed
    22 / 212 (10.38%)
    26 / 212 (12.26%)
    32 / 214 (14.95%)
         occurrences all number
    27
    27
    37
    Oedema
         subjects affected / exposed
    27 / 212 (12.74%)
    25 / 212 (11.79%)
    17 / 214 (7.94%)
         occurrences all number
    35
    29
    24
    Oedema peripheral
         subjects affected / exposed
    72 / 212 (33.96%)
    97 / 212 (45.75%)
    75 / 214 (35.05%)
         occurrences all number
    110
    143
    120
    Pain
         subjects affected / exposed
    8 / 212 (3.77%)
    14 / 212 (6.60%)
    11 / 214 (5.14%)
         occurrences all number
    11
    18
    17
    Pyrexia
         subjects affected / exposed
    20 / 212 (9.43%)
    28 / 212 (13.21%)
    21 / 214 (9.81%)
         occurrences all number
    35
    36
    27
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    26 / 212 (12.26%)
    21 / 212 (9.91%)
    15 / 214 (7.01%)
         occurrences all number
    30
    24
    22
    Dyspnoea
         subjects affected / exposed
    22 / 212 (10.38%)
    26 / 212 (12.26%)
    27 / 214 (12.62%)
         occurrences all number
    24
    30
    34
    Dyspnoea exertional
         subjects affected / exposed
    12 / 212 (5.66%)
    8 / 212 (3.77%)
    10 / 214 (4.67%)
         occurrences all number
    13
    9
    12
    Pharyngolaryngeal Pain
         subjects affected / exposed
    15 / 212 (7.08%)
    11 / 212 (5.19%)
    16 / 214 (7.48%)
         occurrences all number
    16
    13
    19
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    23 / 212 (10.85%)
    21 / 212 (9.91%)
    27 / 214 (12.62%)
         occurrences all number
    25
    25
    30
    Depression
         subjects affected / exposed
    13 / 212 (6.13%)
    11 / 212 (5.19%)
    11 / 214 (5.14%)
         occurrences all number
    15
    13
    12
    Insomnia
         subjects affected / exposed
    60 / 212 (28.30%)
    45 / 212 (21.23%)
    52 / 214 (24.30%)
         occurrences all number
    68
    57
    68
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    41 / 212 (19.34%)
    36 / 212 (16.98%)
    32 / 214 (14.95%)
         occurrences all number
    68
    51
    48
    Blood magnesium decreased
         subjects affected / exposed
    19 / 212 (8.96%)
    12 / 212 (5.66%)
    15 / 214 (7.01%)
         occurrences all number
    22
    18
    25
    Blood phosphorus decreased
         subjects affected / exposed
    10 / 212 (4.72%)
    6 / 212 (2.83%)
    11 / 214 (5.14%)
         occurrences all number
    11
    6
    11
    Cardiac Murmur
         subjects affected / exposed
    11 / 212 (5.19%)
    5 / 212 (2.36%)
    7 / 214 (3.27%)
         occurrences all number
    12
    5
    8
    Hepatic enzyme increased
         subjects affected / exposed
    6 / 212 (2.83%)
    11 / 212 (5.19%)
    9 / 214 (4.21%)
         occurrences all number
    8
    11
    9
    Liver function test abnormal
         subjects affected / exposed
    6 / 212 (2.83%)
    8 / 212 (3.77%)
    11 / 214 (5.14%)
         occurrences all number
    6
    8
    13
    Urine output decreased
         subjects affected / exposed
    8 / 212 (3.77%)
    10 / 212 (4.72%)
    12 / 214 (5.61%)
         occurrences all number
    8
    11
    15
    Weight increased
         subjects affected / exposed
    18 / 212 (8.49%)
    22 / 212 (10.38%)
    14 / 214 (6.54%)
         occurrences all number
    21
    28
    14
    Injury, poisoning and procedural complications
    Complications of transplant surgery
         subjects affected / exposed
    11 / 212 (5.19%)
    10 / 212 (4.72%)
    5 / 214 (2.34%)
         occurrences all number
    15
    14
    9
    Graft dysfunction
         subjects affected / exposed
    41 / 212 (19.34%)
    31 / 212 (14.62%)
    27 / 214 (12.62%)
         occurrences all number
    48
    36
    41
    Incision site complication
         subjects affected / exposed
    46 / 212 (21.70%)
    42 / 212 (19.81%)
    31 / 214 (14.49%)
         occurrences all number
    69
    71
    56
    Post procedural discharge
         subjects affected / exposed
    6 / 212 (2.83%)
    12 / 212 (5.66%)
    10 / 214 (4.67%)
         occurrences all number
    7
    13
    11
    Post procedural pain
         subjects affected / exposed
    42 / 212 (19.81%)
    37 / 212 (17.45%)
    27 / 214 (12.62%)
         occurrences all number
    77
    67
    73
    Therapeutic agent toxicity
         subjects affected / exposed
    14 / 212 (6.60%)
    13 / 212 (6.13%)
    13 / 214 (6.07%)
         occurrences all number
    17
    18
    14
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    11 / 212 (5.19%)
    10 / 212 (4.72%)
    9 / 214 (4.21%)
         occurrences all number
    13
    10
    12
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    27 / 212 (12.74%)
    23 / 212 (10.85%)
    21 / 214 (9.81%)
         occurrences all number
    33
    32
    27
    Headache
         subjects affected / exposed
    50 / 212 (23.58%)
    52 / 212 (24.53%)
    45 / 214 (21.03%)
         occurrences all number
    71
    75
    66
    Hypoaesthesia
         subjects affected / exposed
    5 / 212 (2.36%)
    11 / 212 (5.19%)
    8 / 214 (3.74%)
         occurrences all number
    6
    12
    14
    Paraesthesia
         subjects affected / exposed
    3 / 212 (1.42%)
    13 / 212 (6.13%)
    12 / 214 (5.61%)
         occurrences all number
    3
    13
    17
    Tremor
         subjects affected / exposed
    73 / 212 (34.43%)
    42 / 212 (19.81%)
    75 / 214 (35.05%)
         occurrences all number
    86
    47
    93
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    59 / 212 (27.83%)
    55 / 212 (25.94%)
    68 / 214 (31.78%)
         occurrences all number
    75
    67
    92
    Leukocytosis
         subjects affected / exposed
    4 / 212 (1.89%)
    9 / 212 (4.25%)
    11 / 214 (5.14%)
         occurrences all number
    4
    11
    11
    Leukopenia
         subjects affected / exposed
    33 / 212 (15.57%)
    25 / 212 (11.79%)
    35 / 214 (16.36%)
         occurrences all number
    42
    31
    44
    Neutropenia
         subjects affected / exposed
    9 / 212 (4.25%)
    5 / 212 (2.36%)
    11 / 214 (5.14%)
         occurrences all number
    9
    6
    13
    Polycythaemia
         subjects affected / exposed
    13 / 212 (6.13%)
    9 / 212 (4.25%)
    12 / 214 (5.61%)
         occurrences all number
    16
    10
    15
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    15 / 212 (7.08%)
    18 / 212 (8.49%)
    11 / 214 (5.14%)
         occurrences all number
    17
    19
    17
    Abdominal pain
         subjects affected / exposed
    22 / 212 (10.38%)
    35 / 212 (16.51%)
    26 / 214 (12.15%)
         occurrences all number
    24
    46
    40
    Abdominal pain upper
         subjects affected / exposed
    21 / 212 (9.91%)
    18 / 212 (8.49%)
    16 / 214 (7.48%)
         occurrences all number
    25
    24
    19
    Constipation
         subjects affected / exposed
    68 / 212 (32.08%)
    82 / 212 (38.68%)
    85 / 214 (39.72%)
         occurrences all number
    86
    107
    112
    Diarrhoea
         subjects affected / exposed
    91 / 212 (42.92%)
    53 / 212 (25.00%)
    94 / 214 (43.93%)
         occurrences all number
    146
    74
    140
    Dyspepsia
         subjects affected / exposed
    36 / 212 (16.98%)
    32 / 212 (15.09%)
    32 / 214 (14.95%)
         occurrences all number
    42
    41
    39
    Flatulence
         subjects affected / exposed
    22 / 212 (10.38%)
    14 / 212 (6.60%)
    15 / 214 (7.01%)
         occurrences all number
    24
    17
    16
    Gastrooesophageal reflux disease
         subjects affected / exposed
    5 / 212 (2.36%)
    12 / 212 (5.66%)
    9 / 214 (4.21%)
         occurrences all number
    6
    15
    11
    Gingival hyperplasia
         subjects affected / exposed
    0 / 212 (0.00%)
    15 / 212 (7.08%)
    1 / 214 (0.47%)
         occurrences all number
    0
    18
    1
    Haemorrhoids
         subjects affected / exposed
    5 / 212 (2.36%)
    6 / 212 (2.83%)
    12 / 214 (5.61%)
         occurrences all number
    5
    6
    14
    Loose stools
         subjects affected / exposed
    14 / 212 (6.60%)
    4 / 212 (1.89%)
    11 / 214 (5.14%)
         occurrences all number
    17
    4
    12
    Nausea
         subjects affected / exposed
    71 / 212 (33.49%)
    90 / 212 (42.45%)
    74 / 214 (34.58%)
         occurrences all number
    114
    128
    129
    Vomiting
         subjects affected / exposed
    49 / 212 (23.11%)
    46 / 212 (21.70%)
    51 / 214 (23.83%)
         occurrences all number
    69
    69
    83
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    13 / 212 (6.13%)
    22 / 212 (10.38%)
    18 / 214 (8.41%)
         occurrences all number
    13
    25
    19
    Alopecia
         subjects affected / exposed
    15 / 212 (7.08%)
    4 / 212 (1.89%)
    14 / 214 (6.54%)
         occurrences all number
    15
    6
    14
    Pruritus
         subjects affected / exposed
    20 / 212 (9.43%)
    15 / 212 (7.08%)
    24 / 214 (11.21%)
         occurrences all number
    24
    18
    30
    Rash
         subjects affected / exposed
    10 / 212 (4.72%)
    5 / 212 (2.36%)
    11 / 214 (5.14%)
         occurrences all number
    13
    5
    15
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    23 / 212 (10.85%)
    20 / 212 (9.43%)
    15 / 214 (7.01%)
         occurrences all number
    30
    27
    17
    Haematuria
         subjects affected / exposed
    18 / 212 (8.49%)
    20 / 212 (9.43%)
    15 / 214 (7.01%)
         occurrences all number
    20
    29
    20
    Proteinuria
         subjects affected / exposed
    5 / 212 (2.36%)
    10 / 212 (4.72%)
    13 / 214 (6.07%)
         occurrences all number
    7
    12
    15
    Endocrine disorders
    Hirsutism
         subjects affected / exposed
    0 / 212 (0.00%)
    18 / 212 (8.49%)
    0 / 214 (0.00%)
         occurrences all number
    0
    20
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    26 / 212 (12.26%)
    28 / 212 (13.21%)
    27 / 214 (12.62%)
         occurrences all number
    31
    34
    29
    Back pain
         subjects affected / exposed
    27 / 212 (12.74%)
    29 / 212 (13.68%)
    32 / 214 (14.95%)
         occurrences all number
    30
    37
    35
    Muscle Cramp
         subjects affected / exposed
    17 / 212 (8.02%)
    22 / 212 (10.38%)
    20 / 214 (9.35%)
         occurrences all number
    19
    25
    24
    Osteopenia
         subjects affected / exposed
    12 / 212 (5.66%)
    13 / 212 (6.13%)
    13 / 214 (6.07%)
         occurrences all number
    12
    13
    13
    Osteoporosis
         subjects affected / exposed
    4 / 212 (1.89%)
    5 / 212 (2.36%)
    11 / 214 (5.14%)
         occurrences all number
    4
    5
    11
    Pain in Extremity
         subjects affected / exposed
    27 / 212 (12.74%)
    26 / 212 (12.26%)
    27 / 214 (12.62%)
         occurrences all number
    28
    33
    30
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    11 / 212 (5.19%)
    9 / 212 (4.25%)
    10 / 214 (4.67%)
         occurrences all number
    12
    12
    11
    Escherichia urinary tract infection
         subjects affected / exposed
    11 / 212 (5.19%)
    18 / 212 (8.49%)
    14 / 214 (6.54%)
         occurrences all number
    21
    29
    19
    Herpes simplex
         subjects affected / exposed
    8 / 212 (3.77%)
    9 / 212 (4.25%)
    11 / 214 (5.14%)
         occurrences all number
    9
    11
    12
    Herpes zoster
         subjects affected / exposed
    9 / 212 (4.25%)
    16 / 212 (7.55%)
    10 / 214 (4.67%)
         occurrences all number
    9
    17
    12
    Human polyomavirus infection
         subjects affected / exposed
    10 / 212 (4.72%)
    5 / 212 (2.36%)
    12 / 214 (5.61%)
         occurrences all number
    11
    6
    14
    Nasopharyngitis
         subjects affected / exposed
    12 / 212 (5.66%)
    14 / 212 (6.60%)
    12 / 214 (5.61%)
         occurrences all number
    18
    14
    12
    Oral Candidiasis
         subjects affected / exposed
    9 / 212 (4.25%)
    13 / 212 (6.13%)
    15 / 214 (7.01%)
         occurrences all number
    11
    19
    22
    Sinusitis
         subjects affected / exposed
    7 / 212 (3.30%)
    5 / 212 (2.36%)
    15 / 214 (7.01%)
         occurrences all number
    18
    17
    30
    Upper respiratory tract infection
         subjects affected / exposed
    24 / 212 (11.32%)
    29 / 212 (13.68%)
    27 / 214 (12.62%)
         occurrences all number
    58
    52
    62
    Urinary tract infection
         subjects affected / exposed
    49 / 212 (23.11%)
    42 / 212 (19.81%)
    30 / 214 (14.02%)
         occurrences all number
    89
    88
    60
    Urinary tract infection bacterial
         subjects affected / exposed
    11 / 212 (5.19%)
    9 / 212 (4.25%)
    9 / 214 (4.21%)
         occurrences all number
    19
    12
    11
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    16 / 212 (7.55%)
    4 / 212 (1.89%)
    10 / 214 (4.67%)
         occurrences all number
    20
    5
    16
    Diabetes mellitus
         subjects affected / exposed
    20 / 212 (9.43%)
    9 / 212 (4.25%)
    25 / 214 (11.68%)
         occurrences all number
    36
    16
    39
    Dyslipidaemia
         subjects affected / exposed
    4 / 212 (1.89%)
    6 / 212 (2.83%)
    12 / 214 (5.61%)
         occurrences all number
    8
    11
    25
    Fluid overload
         subjects affected / exposed
    14 / 212 (6.60%)
    9 / 212 (4.25%)
    9 / 214 (4.21%)
         occurrences all number
    17
    13
    14
    Hyperglycaemia
         subjects affected / exposed
    37 / 212 (17.45%)
    28 / 212 (13.21%)
    30 / 214 (14.02%)
         occurrences all number
    54
    37
    47
    Hypercholesterolaemia
         subjects affected / exposed
    10 / 212 (4.72%)
    16 / 212 (7.55%)
    8 / 214 (3.74%)
         occurrences all number
    12
    18
    14
    Hyperkalaemia
         subjects affected / exposed
    48 / 212 (22.64%)
    38 / 212 (17.92%)
    40 / 214 (18.69%)
         occurrences all number
    70
    51
    62
    Hyperlipidaemia
         subjects affected / exposed
    35 / 212 (16.51%)
    52 / 212 (24.53%)
    35 / 214 (16.36%)
         occurrences all number
    57
    65
    52
    Hypocalcaemia
         subjects affected / exposed
    15 / 212 (7.08%)
    25 / 212 (11.79%)
    13 / 214 (6.07%)
         occurrences all number
    24
    31
    20
    Hypokalaemia
         subjects affected / exposed
    31 / 212 (14.62%)
    33 / 212 (15.57%)
    31 / 214 (14.49%)
         occurrences all number
    37
    47
    39
    Hypomagnesaemia
         subjects affected / exposed
    57 / 212 (26.89%)
    44 / 212 (20.75%)
    52 / 214 (24.30%)
         occurrences all number
    79
    57
    71
    Hypophosphataemia
         subjects affected / exposed
    59 / 212 (27.83%)
    45 / 212 (21.23%)
    50 / 214 (23.36%)
         occurrences all number
    65
    52
    56
    Metabolic acidosis
         subjects affected / exposed
    12 / 212 (5.66%)
    11 / 212 (5.19%)
    15 / 214 (7.01%)
         occurrences all number
    15
    13
    19

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 May 2003
    Amendment 1 (May 8, 2003) involved the following changes to the original protocol: · Dosing amounts, schedules, and routes of administration were modified. · Inclusion and exclusion criteria were modified. · The study visit schedule for the initial treatment period was modified. · Hepatic profile sample collection times were modified. · Tests performed at central laboratories were clarified. · Sponsor personnel contact information was updated. · Typographical errors were corrected and minor clerical changes were incorporated.
    13 Nov 2003
    Amendment 2 (November 13, 2003) involved the following changes: · The primary and secondary efficacy assessments were modified. · A section describing interim analyses was added. · The inclusion criteria were clarified. · Descriptions of statistical analyses were modified. · The follow-up duration for adverse events was clarified. · Typographical errors were corrected and minor clerical changes were incorporated.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The clinical continuation phase was terminated by the Sponsor.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/17217442
    For support, Contact us.
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