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    Clinical Trial Results:
    Phase 3b, Randomized, Open-label, Active-controlled Trial Evaluating the Efficacy and Safety of Oral Vadadustat Once Daily (QD) and Three Times Weekly (TIW) for the Maintenance Treatment of Anemia in Hemodialysis Subjects Converting from Erythropoiesis-Stimulating Agents (ESAs)

    Summary
    EudraCT number
    		 2019-004851-36
    Trial protocol
    		 HU   PL   CZ   IT  
    Global end of trial date
    22 Jun 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Sep 2024
    First version publication date
    19 Sep 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    404-201-00012
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04313153
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Akebia Therapeutics
    Sponsor organisation address
    245 First St #1400, Cambridge, Massachusetts, United States, 02142
    Public contact
    Clinical Trial Information Desk, Akebia Therapeutics, Inc., Akebia Therapeutics 245 First St #1400, Cambridge Massachusetts 02142 United States, +1 6178446128, trials@akebia.com
    Scientific contact
    Clinical Trial Information Desk, Akebia Therapeutics, Inc., Akebia Therapeutics 245 First St #1400, Cambridge Massachusetts 02142 United States, +1 6178446128, trials@akebia.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    22 Jun 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Jun 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the efficacy and safety of vadadustat compared to darbepoetin alfa for the maintenance treatment of anemia in hemodialysis participants after conversion from current erythropoiesis-stimulating agent (ESA) therapy.
    Protection of trial subjects
    At the first visit, prior to initiation of any study-related procedures, the parent(s) or legal guardian(s) of the participants gave their written consent to participate in the study after having been informed about the nature and purpose of the study, participation / termination conditions, and risks and benefits. Before the informed consent document was signed, the investigator, or a person designated by the investigator, provided the participant or the participant's legally acceptable representative ample time and opportunity to inquire about details of the trial and to decide whether or not to participate in the trial. All questions about the trial were answered to the satisfaction of the subject or the participant's legally acceptable representative.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 May 2020
    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
    Czechia: 26
    Country: Number of subjects enrolled
    Hungary: 33
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Poland: 26
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    United States: 229
    Worldwide total number of subjects
    319
    EEA total number of subjects
    90
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    193
    From 65 to 84 years
    126
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was a randomized, open-label, active-controlled study of vadadustat versus darbepoetin alfa for the maintenance treatment of anemia in hemodialysis participants, after conversion from erythropoiesis-stimulating agent (ESA therapy).

    Pre-assignment
    Screening details
    		 A total of 319 participants were enrolled in the study. Participants were randomized 1:1:1 to vadadustat once daily (QD), vadadustat three times weekly (TIW), or darbepoetin alfa, stratified with respect to geographic region and mean weekly darbepoetin alfa dose (or ESA equivalent) calculated over a period of 8 weeks prior to Screening Visit 2.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Vadadustat QD
    Arm description
    		 Participants were randomized to receive vadadustat QD orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (less than or equal to [<=] 0.45 micrograms per kilograms per week [mcg/kg/week]), participants received an initial vadadustat daily dose of 300 milligrams (mg) daily. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat daily dose of 450 mg daily. Vadadustat was titrated to achieve and maintain target hemoglobin (Hb) levels. The dose range for titration was 150 to 900 mg vadadustat QD.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vadadustat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One 150 mg or 450 mg vadadustat tablet was to be taken each day.

    Arm title
    		 Vadadustat TIW
    Arm description
    		 Participants were randomized to receive vadadustat TIW orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (<= 0.45 mcg/kg/week), participants received an initial vadadustat dose of 600 mg TIW. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat dose of 750 mg TIW. Vadadustat was titrated to achieve and maintain target Hb levels. The dose range for titration was 150 to 1200 mg vadadustat TIW.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vadadustat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One 150 mg or 450 mg vadadustat tablet was to be taken three times weekly.

    Arm title
    		 Darbepoetin alfa
    Arm description
    		 Participants were randomized to receive darbepoetin alfa as a solution in single-dose prefilled syringes via intravenous (IV) injection through dialysis vascular access. For participants who had received darbepoetin alfa during screening, the initial dosing regimen was approximately the same weekly dose that they were receiving prior to randomization. For participants who had received darbepoetin alfa for the first time, the initial dosing regimen was determined by the United States Package Insert (USPI) or European Union Summary of product characteristics (EU SmPC), per the medical judgment of the investigator.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Darbepoetin alfa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Intravenous use
    Dosage and administration details
    One single-dose prefilled syringes was given by IV injection through dialysis vascular access.

    Number of subjects in period 1
    		Vadadustat QD Vadadustat TIW Darbepoetin alfa
    Started
    105
    106
    108
    Completed
    54
    50
    67
    Not completed
    51
    56
    41
         Adverse Event (Includes Death)
    14
    19
    10
         Consent withdrawn by subject
    7
    6
    2
         Physician decision
    4
    2
    1
         Change In Dialysis Modality
    -
    1
    2
         Unspecified
    5
    3
    2
         Change Of In-Center Hemodialysis From TIW
    1
    -
    -
         Lost to follow-up
    1
    -
    2
         Met Criteria For Trial Medication Stopping Rules
    16
    20
    19
         Receipt Of Any Transplantation
    -
    2
    3
         Lack of efficacy
    3
    3
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Vadadustat QD
    Reporting group description
    		 Participants were randomized to receive vadadustat QD orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (less than or equal to [<=] 0.45 micrograms per kilograms per week [mcg/kg/week]), participants received an initial vadadustat daily dose of 300 milligrams (mg) daily. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat daily dose of 450 mg daily. Vadadustat was titrated to achieve and maintain target hemoglobin (Hb) levels. The dose range for titration was 150 to 900 mg vadadustat QD.

    Reporting group title
    Vadadustat TIW
    Reporting group description
    		 Participants were randomized to receive vadadustat TIW orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (<= 0.45 mcg/kg/week), participants received an initial vadadustat dose of 600 mg TIW. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat dose of 750 mg TIW. Vadadustat was titrated to achieve and maintain target Hb levels. The dose range for titration was 150 to 1200 mg vadadustat TIW.

    Reporting group title
    Darbepoetin alfa
    Reporting group description
    		 Participants were randomized to receive darbepoetin alfa as a solution in single-dose prefilled syringes via intravenous (IV) injection through dialysis vascular access. For participants who had received darbepoetin alfa during screening, the initial dosing regimen was approximately the same weekly dose that they were receiving prior to randomization. For participants who had received darbepoetin alfa for the first time, the initial dosing regimen was determined by the United States Package Insert (USPI) or European Union Summary of product characteristics (EU SmPC), per the medical judgment of the investigator.

    Reporting group values
    		 Vadadustat QD Vadadustat TIW Darbepoetin alfa Total
    Number of subjects
    		 105 106 108 319
    Age categorical
    Units:
        <65 years
    		 59 65 69 193
        ≥65 years
    		 46 41 39 126
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60.9 ( 13.4 ) 61.2 ( 12.5 ) 60.8 ( 12.8 ) -
    Gender categorical
    Units: Subjects
        Female
    		 47 46 43 136
        Male
    		 58 60 65 183
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 1 2 0 3
        Asian
    		 4 1 3 8
        Black Or African American
    		 31 30 33 94
        Native Hawaiian or Other Pacific Islander
    		 0 2 1 3
        White
    		 68 67 71 206
        Not Reported
    		 1 3 0 4
        Reported as Other
    		 0 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Vadadustat QD
    Reporting group description
    		 Participants were randomized to receive vadadustat QD orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (less than or equal to [<=] 0.45 micrograms per kilograms per week [mcg/kg/week]), participants received an initial vadadustat daily dose of 300 milligrams (mg) daily. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat daily dose of 450 mg daily. Vadadustat was titrated to achieve and maintain target hemoglobin (Hb) levels. The dose range for titration was 150 to 900 mg vadadustat QD.

    Reporting group title
    Vadadustat TIW
    Reporting group description
    		 Participants were randomized to receive vadadustat TIW orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (<= 0.45 mcg/kg/week), participants received an initial vadadustat dose of 600 mg TIW. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat dose of 750 mg TIW. Vadadustat was titrated to achieve and maintain target Hb levels. The dose range for titration was 150 to 1200 mg vadadustat TIW.

    Reporting group title
    Darbepoetin alfa
    Reporting group description
    		 Participants were randomized to receive darbepoetin alfa as a solution in single-dose prefilled syringes via intravenous (IV) injection through dialysis vascular access. For participants who had received darbepoetin alfa during screening, the initial dosing regimen was approximately the same weekly dose that they were receiving prior to randomization. For participants who had received darbepoetin alfa for the first time, the initial dosing regimen was determined by the United States Package Insert (USPI) or European Union Summary of product characteristics (EU SmPC), per the medical judgment of the investigator.

    Primary: Change from Baseline in Hb to the average over the Primary evaluation period (PEP) (Weeks 20 to 26)

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    End point title
    		 Change from Baseline in Hb to the average over the Primary evaluation period (PEP) (Weeks 20 to 26) [1]
    End point description
    The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the PEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 20 through 26, regardless of intercurrent events. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as PEP value minus the Baseline value. Randomized population was defined as all participants randomized.
    End point type
    Primary
    End point timeframe
    Baseline; Weeks 20 to 26
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint
    End point values
    		 Vadadustat QD Vadadustat TIW Darbepoetin alfa
    Number of subjects analysed
    105
    106
    108
    Units: Grams per deciliter (g/dL)
        least squares mean (standard error)
    0.07 ( 0.12 )
    -0.19 ( 0.12 )
    0.34 ( 0.12 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Hb to the average over the Secondary evaluation period (SEP) (Weeks 46 to 52)

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    End point title
    		 Change from Baseline in Hb to the average over the Secondary evaluation period (SEP) (Weeks 46 to 52)
    End point description
    The Baseline Hb was defined as the average of the last 2 central laboratory Hb values taken on or prior to the first dose date. The average for the SEP was calculated as the average of all Hb measurements from the central laboratory within the three visit windows during Weeks 46 through 52, regardless of intercurrent events. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with randomization stratification factors and Baseline Hb as covariates. Change from Baseline was calculated as SEP value minus the Baseline value. Randomized population.
    End point type
    Secondary
    End point timeframe
    Baseline; Weeks 46 to 52
    End point values
    		 Vadadustat QD Vadadustat TIW Darbepoetin alfa
    Number of subjects analysed
    105
    106
    108
    Units: g/dL
        least squares mean (standard error)
    0.04 ( 0.15 )
    0.03 ( 0.15 )
    0.44 ( 0.15 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug (Day 1) up to Week 56 (from first dose of study drug to last dose + 4 weeks of follow-up)
    Adverse event reporting additional description
    Treatment-emergent adverse events (TEAEs) are defined as those adverse events (AEs) that began or worsened after treatment initiation and are reported for the Safety Population which consisted of all participants in the randomized population who received at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Vadadustat QD
    Reporting group description
    		 Participants were randomized to receive vadadustat QD orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (less than or equal to [<=] 0.45 micrograms per kilograms per week [mcg/kg/week]), participants received an initial vadadustat daily dose of 300 milligrams (mg) daily. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat daily dose of 450 mg daily. Vadadustat was titrated to achieve and maintain target hemoglobin (Hb) levels. The dose range for titration was 150 to 900 mg vadadustat QD.

    Reporting group title
    Darbepoetin alfa
    Reporting group description
    		 Participants were randomized to receive darbepoetin alfa as a solution in single-dose prefilled syringes via intravenous (IV) injection through dialysis vascular access. For participants who had received darbepoetin alfa during screening, the initial dosing regimen was approximately the same weekly dose that they were receiving prior to randomization. For participants who had received darbepoetin alfa for the first time, the initial dosing regimen was determined by the United States Package Insert (USPI) or European Union Summary of product characteristics (EU SmPC), per the medical judgment of the investigator.

    Reporting group title
    Vadadustat TIW
    Reporting group description
    		 Participants were randomized to receive vadadustat TIW orally. Vadadustat starting daily dose was determined by pre-Baseline mean weekly darbepoetin alfa dose (or ESA equivalent). In the low darbepoetin alfa dose group (<= 0.45 mcg/kg/week), participants received an initial vadadustat dose of 600 mg TIW. In the high darbepoetin alfa dose group (> 0.45 and <= 1.5 mcg/kg/week), participants received an initial vadadustat dose of 750 mg TIW. Vadadustat was titrated to achieve and maintain target Hb levels. The dose range for titration was 150 to 1200 mg vadadustat TIW.

    Serious adverse events
    		 Vadadustat QD Darbepoetin alfa Vadadustat TIW
    Total subjects affected by serious adverse events
         subjects affected / exposed
    47 / 105 (44.76%)
    47 / 108 (43.52%)
    47 / 104 (45.19%)
         number of deaths (all causes)
    12
    7
    9
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of appendix
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Prostate cancer
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Liposarcoma
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glioblastoma
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Gastrointestinal adenocarcinoma
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Vascular disorders
    Hypertensive crisis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Hypertensive emergency
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive urgency
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 108 (0.93%)
    0 / 104 (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
    Jugular vein thrombosis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Steal syndrome
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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 arterial occlusive disease
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral vascular disorder
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Arteriovenous fistula operation
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    General disorders and administration site conditions
    Asthenia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Non-cardiac chest pain
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    3 / 105 (2.86%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Immune system disorders
    Contrast media allergy
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Kidney transplant rejection
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    2 / 108 (1.85%)
    0 / 104 (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
    Reproductive system and breast disorders
    Postmenopausal haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Uterine haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 108 (0.00%)
    0 / 104 (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
    Dyspnoea
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 108 (0.00%)
    0 / 104 (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
    Chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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 respiratory failure
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    3 / 105 (2.86%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory arrest
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Respiratory failure
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Aspartate aminotransferase increased
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Anticoagulation drug level above therapeutic
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Alanine aminotransferase increased
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Troponin increased
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Transaminases increased
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Liver function test increased
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Ankle fracture
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous fistula site complication
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 108 (0.00%)
    0 / 104 (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 fistula site haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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 thrombosis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    3 / 108 (2.78%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous graft thrombosis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fractured sacrum
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Humerus fracture
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         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
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Wrist fracture
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular access site haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Traumatic haemothorax
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Traumatic haematoma
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Post procedural haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Rib fracture
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Spinal compression fracture
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Haemorrhagic arteriovenous malformation
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Cardiac disorders
    Angina pectoris
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute left ventricular failure
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         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 myocardial infarction
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 108 (0.00%)
    6 / 104 (5.77%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 108 (0.93%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         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
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 108 (0.93%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    Cardiac failure
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    1 / 108 (0.93%)
    0 / 104 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         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 failure congestive
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    1 / 108 (0.93%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 108 (0.93%)
    0 / 104 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Coronary artery disease
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    3 / 104 (2.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Nervous system disorders
    Ataxia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Bell's palsy
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Embolic stroke
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Syncope
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Seizure
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Presyncope
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Myelopathy
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Ischaemic stroke
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 108 (0.93%)
    0 / 104 (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
    Haemorrhagic stroke
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Generalised tonic-clonic seizure
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Encephalopathy
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxic encephalopathy
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    3 / 105 (2.86%)
    5 / 108 (4.63%)
    5 / 104 (4.81%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood loss anaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Visual impairment
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Vitreous haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    3 / 104 (2.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Duodenal ulcer haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenitis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Food poisoning
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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 haemorrhagic
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Chronic gastritis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Impaired gastric emptying
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic duct obstruction
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Pancreatitis acute
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    2 / 108 (1.85%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bile duct stenosis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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 and subcutaneous tissue disorders
    Skin ulcer
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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 foot
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Intertrigo
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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 and urinary disorders
    Renal cyst haemorrhage
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    End stage renal disease
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 108 (0.00%)
    0 / 104 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Azotaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Endocrine disorders
    Hyperparathyroidism secondary
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Parathyroid hyperplasia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Intervertebral disc protrusion
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Fracture pain
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Cervical spinal stenosis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 108 (0.93%)
    0 / 104 (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
    Back pain
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    2 / 104 (1.92%)
         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
    Arthritis bacterial
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Asymptomatic COVID-19
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    4 / 108 (3.70%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Device related sepsis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Candida pneumonia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Cellulitis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    2 / 108 (1.85%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cryptococcal fungaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Device related bacteraemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    7 / 105 (6.67%)
    4 / 108 (3.70%)
    8 / 104 (7.69%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    0 / 3
    Diabetic foot infection
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    2 / 108 (1.85%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis intestinal haemorrhagic
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Endocarditis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 108 (0.93%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterococcal bacteraemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media staphylococcal
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Klebsiella sepsis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    2 / 108 (1.85%)
    0 / 104 (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
    Muscle abscess
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Necrotising soft tissue infection
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Osteomyelitis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    2 / 108 (1.85%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gangrene
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    2 / 108 (1.85%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis bacterial
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Pneumonia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    1 / 108 (0.93%)
    3 / 104 (2.88%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pneumonia aspiration
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    Pneumonia staphylococcal
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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 abscess
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    3 / 108 (2.78%)
    3 / 104 (2.88%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Septic shock
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 108 (0.93%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    Staphylococcal osteomyelitis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 108 (0.93%)
    0 / 104 (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
    SARS-CoV-2 sepsis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Vascular graft infection
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Metabolism and nutrition disorders
    Hypocalcaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 108 (0.00%)
    1 / 104 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypervolaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    4 / 108 (3.70%)
    4 / 104 (3.85%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    3 / 108 (2.78%)
    0 / 104 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 108 (0.93%)
    0 / 104 (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
    Failure to thrive
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Hypoglycaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 108 (0.93%)
    2 / 104 (1.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 108 (0.00%)
    0 / 104 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Vadadustat QD Darbepoetin alfa Vadadustat TIW
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    46 / 105 (43.81%)
    46 / 108 (42.59%)
    49 / 104 (47.12%)
    Injury, poisoning and procedural complications
    Fall
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    10 / 105 (9.52%)
    5 / 108 (4.63%)
    6 / 104 (5.77%)
         occurrences all number
    12
    7
    7
    Vascular disorders
    Hypertension
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    6 / 105 (5.71%)
    10 / 108 (9.26%)
    11 / 104 (10.58%)
         occurrences all number
    7
    10
    14
    Blood and lymphatic system disorders
    Anaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    5 / 105 (4.76%)
    7 / 108 (6.48%)
    7 / 104 (6.73%)
         occurrences all number
    5
    9
    7
    General disorders and administration site conditions
    Oedema peripheral
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    6 / 105 (5.71%)
    3 / 108 (2.78%)
    0 / 104 (0.00%)
         occurrences all number
    6
    3
    0
    Gastrointestinal disorders
    Vomiting
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    10 / 105 (9.52%)
    6 / 108 (5.56%)
    4 / 104 (3.85%)
         occurrences all number
    13
    6
    4
    Nausea
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    12 / 105 (11.43%)
    6 / 108 (5.56%)
    6 / 104 (5.77%)
         occurrences all number
    14
    6
    7
    Diarrhoea
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    14 / 105 (13.33%)
    6 / 108 (5.56%)
    15 / 104 (14.42%)
         occurrences all number
    15
    8
    19
    Abdominal pain
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    4 / 105 (3.81%)
    8 / 108 (7.41%)
    4 / 104 (3.85%)
         occurrences all number
    4
    8
    4
    Musculoskeletal and connective tissue disorders
    Back pain
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    2 / 105 (1.90%)
    2 / 108 (1.85%)
    6 / 104 (5.77%)
         occurrences all number
    2
    2
    6
    Infections and infestations
    COVID-19
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    12 / 105 (11.43%)
    10 / 108 (9.26%)
    11 / 104 (10.58%)
         occurrences all number
    12
    10
    12
    Metabolism and nutrition disorders
    Hypoglycaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    6 / 105 (5.71%)
    3 / 108 (2.78%)
    1 / 104 (0.96%)
         occurrences all number
    7
    3
    1
    Hyperkalaemia
    alternative dictionary used: MedDRA 25
         subjects affected / exposed
    4 / 105 (3.81%)
    9 / 108 (8.33%)
    5 / 104 (4.81%)
         occurrences all number
    6
    13
    5

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Mar 2021
    The amendment alters the trial design and/or increases the potential risk to the participant, the currently approved written ICF will require similar modification. In such cases, after approval/favorable opinion of the new ICF by the IRB/IEC, repeat written informed consent will be obtained from participants enrolled in the trial before expecting continued participation and before the amendment-specified changes in the trial are implemented.

    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.
    Per the protocol, all results data are summarized by the arm to which participants were randomized; no separate analysis was performed to report results for initial vadadustat dose received in either of the vadadustat QD or vadadustat TIW arms.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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