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    Clinical Trial Results:
    A multicenter randomized phase II study to determine the optimal first-line chemotherapy regimen in patients with metastatic pancreatic cancer (FOOTPATH)

    Summary
    EudraCT number
    		 2017-003496-54
    Trial protocol
    		 DE  
    Global end of trial date
    24 Oct 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Oct 2026
    First version publication date
    19 Oct 2026
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    FOOTPATH
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03487016
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    LMU Munich
    Sponsor organisation address
    Marchioninistrasse 15, Munich, Germany, 81377
    Public contact
    Study Secretary, Klinikum der Ludwig-Maximilian-Universität München, Klinikum Großhadern, 0049 89440072208, matthias.wolff@med.uni-muenchen.de
    Scientific contact
    Study Secretary, Klinikum der Ludwig-Maximilian-Universität München, Klinikum Großhadern, 0049 89440072208, matthias.wolff@med.uni-muenchen.de
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Sep 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Oct 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Oct 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the optimal first-line regimen in metastatic pancreatic cancer
    Protection of trial subjects
    The trial was conducted in accordance with the German Medicinal Products Act (AMG), ICH-GCP and the Declaration of Helsinki. Protocol version 3.0 was approved by the German competent authority (BfArM) on 16 January 2019; all amendments (final version 7.0, approved 12 September 2022) were approved before implementation. All patients gave written informed consent before any protocol-specific procedure; legal capacity to consent was an inclusion criterion. Eligibility required ECOG performance status 0 to 1 and adequate organ function; patients with severe concomitant disease, hypersensitivity to a study drug, strong CYP3A4 or UGT1A1 inhibitors, known glucuronidation deficiency or complete DPD deficiency were excluded. Women of childbearing potential required a negative pregnancy test and highly effective contraception during treatment and for 7 months after the last dose; men had to use condoms for 6 months. All study drugs are authorised in Germany and were given at established doses and schedules. Treatment continued until progression or unacceptable toxicity, with protocol-defined dose reductions and delays. Adverse events were recorded from informed consent until 28 days after the last dose or the end-of-treatment visit, whichever was longer, and graded according to NCI CTCAE. Serious adverse events had to be reported within 24 hours to the pharmacovigilance contractor of the sponsor (ClinAssess GmbH); related serious adverse events were reportable irrespective of the time since the last dose. S afety data were monitored continuously; no data monitoring committee was installed. Tumour assessments (RECIST 1.1) and CA 19-9 were performed every 8 weeks. Patients were covered by clinical trial insurance as required by the AMG.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Apr 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 274
    Worldwide total number of subjects
    274
    EEA total number of subjects
    274
    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)
    134
    From 65 to 84 years
    140
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Patients were recruited at 38 sites in Germany. The first patient gave informed consent and was randomised on 18 April 2019; the last patient was randomised on 13 July 2022. In total, 303 patients gave informed consent, of whom 274 were randomised 1:1:1 to the three treatment arms.

    Pre-assignment
    Screening details
    		 303 patients gave written informed consent and entered screening. 29 patients were not randomised: 28 did not meet the eligibility criteria (screening failure) and 1 withdrew consent because of clinical deterioration before randomisation. 274 patients were randomised (arm A 90, arm B 92, arm C 92). 9 randomised patients were not treated.

    Period 1
    Period 1 title
    Treatment & follow-up (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Open-label trial; treatment allocation was known to patients, investigators and sponsor after randomisation.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ARM A
    Arm description
    		 Gemcitabine plus nab-paclitaxel Description: Nab-paclitaxel 125 mg/m2 as a 30-minute i.v. infusion followed by gemcitabine 1000 mg/m2 as a 30-minute i.v. infusion on days 1, 8 and 15 of a 28-day cycle, until disease progression or unacceptable toxicity.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    1000 mg/m2 as a 30-minute i.v. infusion on days 1, 8 and 15 of a 28-day cycle, until disease progression or unacceptable toxicity.

    Investigational medicinal product name
    nab-paclitaxcel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Nab-paclitaxel 125 mg/m2 as a 30-minute on days 1, 8 and 15 of a 28-day cycle, until disease progression or unacceptable toxicity.

    Arm title
    		 ARM B
    Arm description
    		 Liposomal irinotecan 70 mg/m2 (irinotecan free base; 80 mg/m2 as irinotecan hydrochloride trihydrate before protocol amendment 2) i.v. over 90 minutes, followed by folinic acid 400 mg/m2 i.v. over 30 minutes and 5-fluorouracil 2400 mg/m2 i.v. over 46 hours, on day 1 of a 14-day cycle, until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Liposomal irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Liposomal irinotecan 70 mg/m2 (irinotecan free base; 80 mg/m2 as irinotecan hydrochloride trihydrate i.v. over 90 minutes until disease progression or unacceptable toxicity.

    Investigational medicinal product name
    Folinic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    folinic acid 400 mg/m2 i.v. over 30 minutes

    Investigational medicinal product name
    5-FU
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    2400 mg/m2 i.v. over 46 hours, on day 1 of a 14-day cycle, until disease progression or unacceptable toxicity.

    Arm title
    		 ARM C
    Arm description
    		 Alternating 14-day cycles of NAPOLI (liposomal irinotecan 70 mg/m2, folinic acid 400 mg/m2, 5-fluorouracil 2400 mg/m2 over 46 hours) and mFOLFOX6 (oxaliplatin 85 mg/m2 i.v. over 2 to 6 hours, folinic acid 400 mg/m2, 5-fluorouracil 2400 mg/m2 over 46 hours), starting with NAPOLI, until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Liposomal irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Liposomal irinotecan 70 mg/m2 (irinotecan free base; 80 mg/m2 as irinotecan hydrochloride trihydrate i.v. over 90 minutes until disease progression or unacceptable toxicity.

    Investigational medicinal product name
    Folinic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    folinic acid 400 mg/m2 i.v. over 30 minutes

    Investigational medicinal product name
    5-FU
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    2400 mg/m2 i.v. over 46 hours, on day 1 of a 14-day cycle, until disease progression or unacceptable toxicity.

    Investigational medicinal product name
    Oxaliplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    85 mg/m2 i.v. over 2 to 6 hours

    Number of subjects in period 1
    		ARM A ARM B ARM C
    Started
    90
    92
    92
    Received at least one dose in study
    89
    86
    90
    Completed
    85
    82
    83
    Not completed
    5
    10
    9
         Consent withdrawn by subject
    2
    7
    2
         Physician decision
    1
    2
    -
         Lost to follow-up
    2
    1
    6
         Protocol deviation
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment & follow-up
    Reporting group description
    		 -

    Reporting group values
    		 Treatment & follow-up Total
    Number of subjects
    		 274 274
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 134 134
        From 65-84 years
    		 140 140
    Gender categorical
    Units: Subjects
        Female
    		 137 137
        Male
    		 137 137

    End points

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    End points reporting groups
    Reporting group title
    ARM A
    Reporting group description
    		 Gemcitabine plus nab-paclitaxel Description: Nab-paclitaxel 125 mg/m2 as a 30-minute i.v. infusion followed by gemcitabine 1000 mg/m2 as a 30-minute i.v. infusion on days 1, 8 and 15 of a 28-day cycle, until disease progression or unacceptable toxicity.

    Reporting group title
    ARM B
    Reporting group description
    		 Liposomal irinotecan 70 mg/m2 (irinotecan free base; 80 mg/m2 as irinotecan hydrochloride trihydrate before protocol amendment 2) i.v. over 90 minutes, followed by folinic acid 400 mg/m2 i.v. over 30 minutes and 5-fluorouracil 2400 mg/m2 i.v. over 46 hours, on day 1 of a 14-day cycle, until disease progression or unacceptable toxicity.

    Reporting group title
    ARM C
    Reporting group description
    		 Alternating 14-day cycles of NAPOLI (liposomal irinotecan 70 mg/m2, folinic acid 400 mg/m2, 5-fluorouracil 2400 mg/m2 over 46 hours) and mFOLFOX6 (oxaliplatin 85 mg/m2 i.v. over 2 to 6 hours, folinic acid 400 mg/m2, 5-fluorouracil 2400 mg/m2 over 46 hours), starting with NAPOLI, until disease progression or unacceptable toxicity.

    Primary: Progression free survival

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    End point title
    		 Progression free survival
    End point description
    End point type
    Primary
    End point timeframe
    From randomisation until objective disease progression or death from any cause, whichever occurred first. Tumour assessments every 8 weeks. Final analysis at data extract 10 September 2025 (maximum observed time to event 49.0 months).
    End point values
    		 ARM A ARM B ARM C
    Number of subjects analysed
    89
    86
    90
    Units: months
        median (confidence interval 86.6%)
    4.6 (3.7 to 5.6)
    3.1 (2.1 to 3.9)
    6.2 (4.5 to 7.3)
    Statistical analysis title
    		 Statistical analysis 1 (A vs B)
    Statistical analysis description
    Two-sided log-rank test at alpha 0.134 (equivalent to the pre-specified one-sided alpha of 0.067 per comparison). Hazard ratio from a Cox proportional hazards model with arm A as reference; HR below 1 favours arm B. Full analysis set. Comparison groups: Period 1 ARM A und Period 1 ARM B
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    175
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1681
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.237
    Confidence interval
         level
    		 86.6%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.562
    Statistical analysis title
    		 Statistical analysis 2 (A vs C)
    Statistical analysis description
    Two-sided log-rank test at alpha 0.134 (equivalent to the pre-specified one-sided alpha of 0.067 per comparison). Hazard ratio from a Cox proportional hazards model with arm A as reference; HR below 1 favours arm C. Full analysis set.
    Comparison groups
    ARM A v ARM C
    Number of subjects included in analysis
    179
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0205
    Method
    		 Logrank
    Confidence interval
         level
    		 86.6%
         sides
    2-sided
         lower limit
    		 0.553
         upper limit
    		 0.883

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent adverse events from first administration of study medication until 28 days after the last administration. Safety set: all randomised patients who received at least one dose (N=265). Data extract 10 September 2025.
    Adverse event reporting additional description
    Adverse events were graded according to NCI CTCAE version 5.0 and coded by MedDRA preferred term and system organ class. Frequencies are patient-based: each preferred term is counted once per patient with the highest grade. Per protocol, progression of the underlying pancreatic cancer, including progression with fatal outcome, was not recorded as a
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28
    Reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Arm A: Gemcitabine plus nab-paclitaxel. Description: Patients randomised to arm A who received at least one dose of study treatment (safety set).

    Reporting group title
    Arm B
    Reporting group description
    		 Arm B: NAPOLI. Description: Patients randomised to arm B who received at least one dose of study treatment (safety set).

    Reporting group title
    Arm C
    Reporting group description
    		 Arm C: Sequential NAPOLI and mFOLFOX6. Description: Patients randomised to arm C who received at least one dose of study treatment (safety set).

    Serious adverse events
    		 Arm A Arm B Arm C
    Total subjects affected by serious adverse events
         subjects affected / exposed
    52 / 89 (58.43%)
    51 / 86 (59.30%)
    53 / 90 (58.89%)
         number of deaths (all causes)
    84
    81
    78
         number of deaths resulting from adverse events
    12
    7
    6
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bowen's disease
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Lymphangioma
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Tumour associated fever
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    1 / 89 (1.12%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Axillary vein thrombosis
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Hypertensive crisis
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subclavian vein thrombosis
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Surgical and medical procedures
    Coeliac plexus block
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Death
         subjects affected / exposed
    2 / 89 (2.25%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    1 / 2
    0 / 1
    0 / 1
    Fatigue
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    3 / 89 (3.37%)
    4 / 86 (4.65%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 89 (0.00%)
    2 / 86 (2.33%)
    0 / 90 (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
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    2 / 90 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    Oedema mucosal
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Pain
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 89 (2.25%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute interstitial pneumonitis
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Apnoea
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Dyspnoea
         subjects affected / exposed
    2 / 89 (2.25%)
    0 / 86 (0.00%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Interstitial lung disease
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Pleural effusion
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Pneumothorax
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Pulmonary embolism
         subjects affected / exposed
    4 / 89 (4.49%)
    4 / 86 (4.65%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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 failure
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    1 / 89 (1.12%)
    1 / 86 (1.16%)
    0 / 90 (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
    Injury, poisoning and procedural complications
    Femoral neck fracture
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Post procedural fever
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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 disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Cardiac arrest
         subjects affected / exposed
    1 / 89 (1.12%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    Cardiac failure
         subjects affected / exposed
    1 / 89 (1.12%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         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 fibrillation
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Nervous system disorders
    Basal ganglia haemorrhage
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disturbance in attention
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Ischaemic cerebral infarction
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         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 stroke
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Middle cerebral artery stroke
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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 and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 89 (3.37%)
    0 / 86 (0.00%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Pancytopenia
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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 pain
         subjects affected / exposed
    1 / 89 (1.12%)
    1 / 86 (1.16%)
    3 / 90 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Acute abdomen
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 89 (1.12%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 89 (3.37%)
    0 / 86 (0.00%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 89 (3.37%)
    5 / 86 (5.81%)
    8 / 90 (8.89%)
         occurrences causally related to treatment / all
    2 / 3
    5 / 5
    6 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal stenosis
         subjects affected / exposed
    0 / 89 (0.00%)
    2 / 86 (2.33%)
    0 / 90 (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
    Dysphagia
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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 haemorrhage
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric perforation
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Gastric stenosis
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Ileus
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mechanical ileus
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    3 / 89 (3.37%)
    2 / 86 (2.33%)
    2 / 90 (2.22%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Pancreatic failure
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Splenic artery aneurysm
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Subileus
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    2 / 90 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Vomiting
         subjects affected / exposed
    1 / 89 (1.12%)
    2 / 86 (2.33%)
    4 / 90 (4.44%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stenosis
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    3 / 89 (3.37%)
    2 / 86 (2.33%)
    4 / 90 (4.44%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    3 / 90 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Liver disorder
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Ocular icterus
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Portal vein stenosis
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Acute kidney injury
         subjects affected / exposed
    1 / 89 (1.12%)
    3 / 86 (3.49%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Calculus urinary
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
         subjects affected / exposed
    1 / 89 (1.12%)
    1 / 86 (1.16%)
    0 / 90 (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 retention
         subjects affected / exposed
    0 / 89 (0.00%)
    2 / 86 (2.33%)
    0 / 90 (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
    Urinary tract disorder
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Back pain
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Atypical pneumonia
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Bacterial infection
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    COVID-19
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Candida sepsis
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Catheter site infection
         subjects affected / exposed
    2 / 89 (2.25%)
    1 / 86 (1.16%)
    2 / 90 (2.22%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis infective
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Cystitis
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Device related infection
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    2 / 89 (2.25%)
    2 / 86 (2.33%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    3 / 89 (3.37%)
    2 / 86 (2.33%)
    2 / 90 (2.22%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Klebsiella infection
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Klebsiella sepsis
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Liver abscess
         subjects affected / exposed
    2 / 89 (2.25%)
    0 / 86 (0.00%)
    0 / 90 (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
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    Peritonitis
         subjects affected / exposed
    1 / 89 (1.12%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    2 / 89 (2.25%)
    0 / 86 (0.00%)
    0 / 90 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 89 (1.12%)
    2 / 86 (2.33%)
    4 / 90 (4.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Rotavirus infection
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Sepsis
         subjects affected / exposed
    5 / 89 (5.62%)
    1 / 86 (1.16%)
    2 / 90 (2.22%)
         occurrences causally related to treatment / all
    2 / 5
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    1 / 2
    Spontaneous bacterial peritonitis
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 89 (0.00%)
    2 / 86 (2.33%)
    0 / 90 (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
    Urinary tract infection
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    0 / 90 (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
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 89 (0.00%)
    1 / 86 (1.16%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 89 (1.12%)
    0 / 86 (0.00%)
    0 / 90 (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
    Hyperglycaemia
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    4 / 90 (4.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 89 (0.00%)
    0 / 86 (0.00%)
    1 / 90 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         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
    		 Arm A Arm B Arm C
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    88 / 89 (98.88%)
    77 / 86 (89.53%)
    86 / 90 (95.56%)
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    5 / 89 (5.62%)
    5 / 86 (5.81%)
    2 / 90 (2.22%)
         occurrences all number
    5
    5
    2
    Hypertension
         subjects affected / exposed
    4 / 89 (4.49%)
    3 / 86 (3.49%)
    11 / 90 (12.22%)
         occurrences all number
    7
    3
    11
    Hypotension
         subjects affected / exposed
    1 / 89 (1.12%)
    4 / 86 (4.65%)
    5 / 90 (5.56%)
         occurrences all number
    1
    4
    5
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    2 / 89 (2.25%)
    0 / 86 (0.00%)
    5 / 90 (5.56%)
         occurrences all number
    2
    0
    5
    Fatigue
         subjects affected / exposed
    40 / 89 (44.94%)
    36 / 86 (41.86%)
    40 / 90 (44.44%)
         occurrences all number
    57
    51
    60
    General physical health deterioration
         subjects affected / exposed
    4 / 89 (4.49%)
    6 / 86 (6.98%)
    3 / 90 (3.33%)
         occurrences all number
    4
    9
    4
    Localised oedema
         subjects affected / exposed
    5 / 89 (5.62%)
    1 / 86 (1.16%)
    2 / 90 (2.22%)
         occurrences all number
    11
    1
    2
    Mucosal inflammation
         subjects affected / exposed
    6 / 89 (6.74%)
    10 / 86 (11.63%)
    13 / 90 (14.44%)
         occurrences all number
    9
    21
    20
    Oedema
         subjects affected / exposed
    6 / 89 (6.74%)
    5 / 86 (5.81%)
    7 / 90 (7.78%)
         occurrences all number
    7
    5
    7
    Oedema peripheral
         subjects affected / exposed
    17 / 89 (19.10%)
    10 / 86 (11.63%)
    5 / 90 (5.56%)
         occurrences all number
    22
    11
    5
    Pain
         subjects affected / exposed
    9 / 89 (10.11%)
    11 / 86 (12.79%)
    5 / 90 (5.56%)
         occurrences all number
    13
    13
    7
    Pyrexia
         subjects affected / exposed
    14 / 89 (15.73%)
    6 / 86 (6.98%)
    9 / 90 (10.00%)
         occurrences all number
    33
    7
    11
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    10 / 89 (11.24%)
    3 / 86 (3.49%)
    4 / 90 (4.44%)
         occurrences all number
    10
    4
    4
    Dyspnoea
         subjects affected / exposed
    12 / 89 (13.48%)
    5 / 86 (5.81%)
    6 / 90 (6.67%)
         occurrences all number
    13
    5
    6
    Epistaxis
         subjects affected / exposed
    19 / 89 (21.35%)
    4 / 86 (4.65%)
    4 / 90 (4.44%)
         occurrences all number
    26
    4
    4
    Psychiatric disorders
    Sleep disorder
         subjects affected / exposed
    3 / 89 (3.37%)
    2 / 86 (2.33%)
    8 / 90 (8.89%)
         occurrences all number
    3
    2
    8
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    9 / 89 (10.11%)
    1 / 86 (1.16%)
    5 / 90 (5.56%)
         occurrences all number
    11
    1
    5
    Aspartate aminotransferase increased
         subjects affected / exposed
    8 / 89 (8.99%)
    0 / 86 (0.00%)
    5 / 90 (5.56%)
         occurrences all number
    10
    0
    5
    Blood alkaline phosphatase increased
         subjects affected / exposed
    11 / 89 (12.36%)
    5 / 86 (5.81%)
    5 / 90 (5.56%)
         occurrences all number
    14
    5
    7
    C-reactive protein increased
         subjects affected / exposed
    9 / 89 (10.11%)
    3 / 86 (3.49%)
    3 / 90 (3.33%)
         occurrences all number
    12
    4
    3
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    13 / 89 (14.61%)
    6 / 86 (6.98%)
    8 / 90 (8.89%)
         occurrences all number
    17
    6
    10
    Weight decreased
         subjects affected / exposed
    5 / 89 (5.62%)
    14 / 86 (16.28%)
    6 / 90 (6.67%)
         occurrences all number
    5
    14
    7
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 89 (5.62%)
    1 / 86 (1.16%)
    4 / 90 (4.44%)
         occurrences all number
    5
    1
    13
    Neuropathy peripheral
         subjects affected / exposed
    36 / 89 (40.45%)
    14 / 86 (16.28%)
    36 / 90 (40.00%)
         occurrences all number
    53
    18
    72
    Peripheral sensory neuropathy
         subjects affected / exposed
    5 / 89 (5.62%)
    4 / 86 (4.65%)
    4 / 90 (4.44%)
         occurrences all number
    5
    4
    5
    Taste disorder
         subjects affected / exposed
    9 / 89 (10.11%)
    2 / 86 (2.33%)
    7 / 90 (7.78%)
         occurrences all number
    9
    2
    7
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    37 / 89 (41.57%)
    16 / 86 (18.60%)
    15 / 90 (16.67%)
         occurrences all number
    61
    19
    30
    Leukopenia
         subjects affected / exposed
    25 / 89 (28.09%)
    3 / 86 (3.49%)
    6 / 90 (6.67%)
         occurrences all number
    55
    3
    7
    Lymphopenia
         subjects affected / exposed
    5 / 89 (5.62%)
    1 / 86 (1.16%)
    4 / 90 (4.44%)
         occurrences all number
    7
    1
    4
    Neutropenia
         subjects affected / exposed
    31 / 89 (34.83%)
    8 / 86 (9.30%)
    15 / 90 (16.67%)
         occurrences all number
    86
    8
    33
    Thrombocytopenia
         subjects affected / exposed
    33 / 89 (37.08%)
    2 / 86 (2.33%)
    7 / 90 (7.78%)
         occurrences all number
    86
    2
    11
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 89 (2.25%)
    3 / 86 (3.49%)
    6 / 90 (6.67%)
         occurrences all number
    2
    3
    6
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    8 / 89 (8.99%)
    13 / 86 (15.12%)
    18 / 90 (20.00%)
         occurrences all number
    11
    16
    25
    Abdominal pain upper
         subjects affected / exposed
    3 / 89 (3.37%)
    4 / 86 (4.65%)
    6 / 90 (6.67%)
         occurrences all number
    3
    4
    8
    Ascites
         subjects affected / exposed
    3 / 89 (3.37%)
    6 / 86 (6.98%)
    4 / 90 (4.44%)
         occurrences all number
    4
    6
    4
    Constipation
         subjects affected / exposed
    19 / 89 (21.35%)
    18 / 86 (20.93%)
    20 / 90 (22.22%)
         occurrences all number
    31
    25
    27
    Diarrhoea
         subjects affected / exposed
    34 / 89 (38.20%)
    46 / 86 (53.49%)
    41 / 90 (45.56%)
         occurrences all number
    46
    82
    74
    Dry mouth
         subjects affected / exposed
    4 / 89 (4.49%)
    7 / 86 (8.14%)
    3 / 90 (3.33%)
         occurrences all number
    4
    7
    3
    Nausea
         subjects affected / exposed
    36 / 89 (40.45%)
    41 / 86 (47.67%)
    42 / 90 (46.67%)
         occurrences all number
    59
    59
    75
    Stomatitis
         subjects affected / exposed
    3 / 89 (3.37%)
    6 / 86 (6.98%)
    11 / 90 (12.22%)
         occurrences all number
    6
    8
    17
    Vomiting
         subjects affected / exposed
    18 / 89 (20.22%)
    26 / 86 (30.23%)
    24 / 90 (26.67%)
         occurrences all number
    30
    34
    32
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    41 / 89 (46.07%)
    16 / 86 (18.60%)
    19 / 90 (21.11%)
         occurrences all number
    48
    18
    20
    Dry skin
         subjects affected / exposed
    4 / 89 (4.49%)
    6 / 86 (6.98%)
    10 / 90 (11.11%)
         occurrences all number
    5
    6
    10
    Rash
         subjects affected / exposed
    14 / 89 (15.73%)
    3 / 86 (3.49%)
    6 / 90 (6.67%)
         occurrences all number
    18
    4
    7
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    6 / 89 (6.74%)
    4 / 86 (4.65%)
    7 / 90 (7.78%)
         occurrences all number
    7
    4
    8
    Infections and infestations
    COVID-19
         subjects affected / exposed
    6 / 89 (6.74%)
    1 / 86 (1.16%)
    9 / 90 (10.00%)
         occurrences all number
    7
    1
    9
    Infection
         subjects affected / exposed
    6 / 89 (6.74%)
    3 / 86 (3.49%)
    2 / 90 (2.22%)
         occurrences all number
    7
    4
    2
    Urinary tract infection
         subjects affected / exposed
    6 / 89 (6.74%)
    0 / 86 (0.00%)
    5 / 90 (5.56%)
         occurrences all number
    6
    0
    5
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    15 / 89 (16.85%)
    18 / 86 (20.93%)
    16 / 90 (17.78%)
         occurrences all number
    16
    18
    20
    Hypoalbuminaemia
         subjects affected / exposed
    4 / 89 (4.49%)
    8 / 86 (9.30%)
    3 / 90 (3.33%)
         occurrences all number
    6
    9
    4
    Hypokalaemia
         subjects affected / exposed
    7 / 89 (7.87%)
    16 / 86 (18.60%)
    9 / 90 (10.00%)
         occurrences all number
    7
    22
    14
    Hyponatraemia
         subjects affected / exposed
    5 / 89 (5.62%)
    3 / 86 (3.49%)
    4 / 90 (4.44%)
         occurrences all number
    5
    4
    8

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 May 2019
    Protocol V3.0 to V4.0 (10.05.2019) Synopse V3.0 (30.04.2019), Patient information V4.0 (30.04.2019)
    19 Dec 2019
    Protocol V4.0 to V5.0 (16.12.2019) Synopse V4.0 (16.12.2019)
    31 Aug 2020
    Protocol V5.0 to V6.0 (15.07.2020) Synopse V5.0 (15.07.2020) Patient information V6.0 (15.07.2020)
    24 Aug 2022
    Protocol V7.0 (27.05.2022) Patient information V7.0, Addendum 1.0 to patient information (27.05.2022)

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

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