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    Clinical Trial Results:
    An open-label early access phase IIIb study of trifluridine / tipiracil (S 95005/TAS-102) in patients with a pretreated metastatic colorectal cancer (PRECONNECT study).

    Summary
    EudraCT number
    		 2016-002311-18
    Trial protocol
    		 ES   BE   PT   PL   SI   FR   SK   BG   HR   IT   RO  
    Global end of trial date
    30 Nov 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Nov 2021
    First version publication date
    06 Nov 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CL3-95005-004
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03306394
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Institut de Recherches Internationales Servier
    Sponsor organisation address
    50 rue Carnot, Suresnes, France, 92284
    Public contact
    Clinical Studies Department, Institut de Recherches Internationales Servier, +33 1.55.72.43.66, clinicaltrials@servier.com
    Scientific contact
    Clinical Studies Department, Institut de Recherches Internationales Servier, +33 1.55.72.43.66, clinicaltrials@servier.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
    30 Nov 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Nov 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Nov 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to collect additional safety data during treatment with trifluridine / tipiracil in patients with a pretreated metastatic colorectal cancer (mCRC).
    Protection of trial subjects
    This study was conducted in accordance with Good Clinical Practice standards, ethical principles stated in the Declaration of Helsinki and applicable regulatory requirements. After the subject has ended his/her participation in the trial, the investigator provided appropriate medication and/or arranged access to appropriate care for the patient.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Nov 2016
    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
    Australia: 70
    Country: Number of subjects enrolled
    Brazil: 55
    Country: Number of subjects enrolled
    Panama: 17
    Country: Number of subjects enrolled
    Turkey: 100
    Country: Number of subjects enrolled
    Ukraine: 12
    Country: Number of subjects enrolled
    Belgium: 45
    Country: Number of subjects enrolled
    Bulgaria: 12
    Country: Number of subjects enrolled
    Croatia: 16
    Country: Number of subjects enrolled
    France: 292
    Country: Number of subjects enrolled
    Ireland: 7
    Country: Number of subjects enrolled
    Italy: 161
    Country: Number of subjects enrolled
    Poland: 54
    Country: Number of subjects enrolled
    Portugal: 24
    Country: Number of subjects enrolled
    Romania: 30
    Country: Number of subjects enrolled
    Slovakia: 15
    Country: Number of subjects enrolled
    Slovenia: 4
    Worldwide total number of subjects
    914
    EEA total number of subjects
    660
    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)
    525
    From 65 to 84 years
    387
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 Investigators were oncologists.

    Pre-assignment
    Screening details
    		 Male or female patients aged ≥18 years old with metastatic colorectal cancer (mCRC) previously treated by at least 2 prior regimens of standard chemotherapies for mCRC and was refractory or intolerant to those chemotherapies. Of note, 916 patients were enrolled in the study: 914 were treated and 2 not treated.

    Period 1
    Period 1 title
    Treatment period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 S95005
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    S95005
    Investigational medicinal product code
    Other name
    Trifluridine-tipiracil
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    S95005 was administered orally twice a day (35 mg/m²/dose) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest.

    Number of subjects in period 1
    		S95005
    Started
    914
    Completed
    0
    Not completed
    914
         Physician decision
    14
         Adverse event, non-fatal
    55
         Study termination by sponsor
    20
         Progressive disease
    736
         Commercial availability of the product
    68
         Lost to follow-up
    3
         Non-medical reason
    18

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    S95005
    Reporting group description
    		 -

    Reporting group values
    		 S95005 Total
    Number of subjects
    		 914 914
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 525 525
        From 65-84 years
    		 387 387
        85 years and over
    		 2 2
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.5 ± 10.6 -
    Gender categorical
    Units: Subjects
        Female
    		 373 373
        Male
    		 541 541

    End points

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    End points reporting groups
    Reporting group title
    S95005
    Reporting group description
    		 -

    Primary: Adverse events

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    End point title
    		 Adverse events [1]
    End point description
    The primary objective of this study was to collect additional safety data during treatment with trifluridine/tipiracil in patients with a pretreated mCRC. The number of subjects affected by adverse events is given in the present endpoints section. Description of serious and non-serious adverse events is provided in the adverse events section.
    End point type
    Primary
    End point timeframe
    See the section adverse events.
    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: No statistical analyses for this end point
    End point values
    		 S95005
    Number of subjects analysed
    914
    Units: Number of patients affected
        number (not applicable)
    884
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events that occurred or worsened or became serious between the first and the last IMP intake + 35 days (both included).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    S95005
    Reporting group description
    		 -

    Serious adverse events
    		 S95005
    Total subjects affected by serious adverse events
         subjects affected / exposed
    335 / 914 (36.65%)
         number of deaths (all causes)
    87
         number of deaths resulting from adverse events
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    9 / 914 (0.98%)
         occurrences causally related to treatment / all
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    Intracranial tumour haemorrhage
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Malignant ascites
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    124 / 914 (13.57%)
         occurrences causally related to treatment / all
    3 / 124
         deaths causally related to treatment / all
    2 / 54
    Malignant pleural effusion
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to biliary tract
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to bladder
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Metastases to bone
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    20 / 914 (2.19%)
         occurrences causally related to treatment / all
    0 / 20
         deaths causally related to treatment / all
    0 / 3
    Metastases to kidney
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to liver
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Metastases to lung
         subjects affected / exposed
    4 / 914 (0.44%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    Metastases to muscle
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to peritoneum
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Metastases to pleura
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Metastases to retroperitoneum
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to spine
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastasis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tumour compression
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Hypertension
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    6 / 914 (0.66%)
         occurrences causally related to treatment / all
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypotension
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    Death
         subjects affected / exposed
    5 / 914 (0.55%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    1 / 5
    Chest pain
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fatigue
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Generalised oedema
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    General physical health deterioration
         subjects affected / exposed
    20 / 914 (2.19%)
         occurrences causally related to treatment / all
    3 / 20
         deaths causally related to treatment / all
    0 / 8
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Oedema peripheral
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
         subjects affected / exposed
    8 / 914 (0.88%)
         occurrences causally related to treatment / all
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Perineal induration
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Prostatitis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Bronchopleural fistula
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    4 / 914 (0.44%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Epistaxis
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
         subjects affected / exposed
    8 / 914 (0.88%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 3
    Pulmonary embolism
         subjects affected / exposed
    10 / 914 (1.09%)
         occurrences causally related to treatment / all
    2 / 10
         deaths causally related to treatment / all
    0 / 0
    Pulmonary infarction
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory distress
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory failure
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Psychiatric disorders
    Anxiety disorder
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Confusional state
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Delirium tremens
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Delirium
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hallucination
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Anaemia postoperative
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bladder injury
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fall
         subjects affected / exposed
    5 / 914 (0.55%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Incision site haematoma
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract stoma complication
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Vascular access malfunction
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Myocardial infarction
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Nervous system disorders
    Coma hepatic
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Apraxia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cauda equina syndrome
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dizziness
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Headache
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Febrile convulsion
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neuralgia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Status epilepticus
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Syncope
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vertigo CNS origin
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    34 / 914 (3.72%)
         occurrences causally related to treatment / all
    28 / 37
         deaths causally related to treatment / all
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Anaemia of malignant disease
         subjects affected / exposed
    4 / 914 (0.44%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    9 / 914 (0.98%)
         occurrences causally related to treatment / all
    10 / 10
         deaths causally related to treatment / all
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Lymphopenia
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Pancytopenia
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Neutropenia
         subjects affected / exposed
    20 / 914 (2.19%)
         occurrences causally related to treatment / all
    25 / 25
         deaths causally related to treatment / all
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    5 / 914 (0.55%)
         occurrences causally related to treatment / all
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Blindness unilateral
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Retinal artery thrombosis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal incarcerated hernia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal pain
         subjects affected / exposed
    12 / 914 (1.31%)
         occurrences causally related to treatment / all
    2 / 13
         deaths causally related to treatment / all
    0 / 1
    Abdominal pain upper
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal strangulated hernia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ascites
         subjects affected / exposed
    11 / 914 (1.20%)
         occurrences causally related to treatment / all
    0 / 11
         deaths causally related to treatment / all
    0 / 2
    Anal haemorrhage
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Constipation
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    11 / 914 (1.20%)
         occurrences causally related to treatment / all
    11 / 12
         deaths causally related to treatment / all
    1 / 1
    Dysphagia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Faecaloma
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastric stenosis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal obstruction
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal toxicity
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ileus
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    16 / 914 (1.75%)
         occurrences causally related to treatment / all
    2 / 16
         deaths causally related to treatment / all
    0 / 3
    Intestinal perforation
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Large intestinal stenosis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malignant gastrointestinal obstruction
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Mouth ulceration
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nausea
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatic failure
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peritoneocutaneous fistula
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Stomatitis
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Subileus
         subjects affected / exposed
    6 / 914 (0.66%)
         occurrences causally related to treatment / all
    2 / 6
         deaths causally related to treatment / all
    0 / 1
    Varices oesophageal
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    14 / 914 (1.53%)
         occurrences causally related to treatment / all
    8 / 16
         deaths causally related to treatment / all
    1 / 2
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bile duct stenosis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholangitis
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Biliary dilatation
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cholecystitis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic failure
         subjects affected / exposed
    10 / 914 (1.09%)
         occurrences causally related to treatment / all
    2 / 10
         deaths causally related to treatment / all
    1 / 4
    Mixed liver injury
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Jaundice
         subjects affected / exposed
    10 / 914 (1.09%)
         occurrences causally related to treatment / all
    0 / 10
         deaths causally related to treatment / all
    0 / 3
    Portal hypertension
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    4 / 914 (0.44%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 1
    Calculus urinary
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Haematuria
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Nephropathy toxic
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Proteinuria
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Renal failure
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis reactive
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Back pain
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pathological fracture
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Abdominal sepsis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Abdominal wall abscess
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Aspergilloma
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bacterial pyelonephritis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Biliary tract infection
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Biliary sepsis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis gangrenous
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cystitis escherichia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cytomegalovirus colitis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia pyelonephritis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    4 / 914 (0.44%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    Infection
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Listeria sepsis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Liver abscess
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Lymphangitis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Medical device site infection
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Muscle abscess
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    4 / 914 (0.44%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Pneumonia
         subjects affected / exposed
    21 / 914 (2.30%)
         occurrences causally related to treatment / all
    4 / 21
         deaths causally related to treatment / all
    0 / 3
    Pneumonia pseudomonal
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psoas abscess
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyopneumothorax
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    5 / 914 (0.55%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    0 / 1
    Septic shock
         subjects affected / exposed
    4 / 914 (0.44%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    Spinal cord infection
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Stenotrophomonas sepsis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tracheobronchitis bacterial
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection staphylococcal
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular device infection
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Decreased appetite
         subjects affected / exposed
    5 / 914 (0.55%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Dehydration
         subjects affected / exposed
    8 / 914 (0.88%)
         occurrences causally related to treatment / all
    4 / 8
         deaths causally related to treatment / all
    0 / 1
    Hypocalcaemia
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 914 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    3 / 914 (0.33%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Steroid diabetes
         subjects affected / exposed
    1 / 914 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 S95005
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    839 / 914 (91.79%)
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    57 / 914 (6.24%)
         occurrences all number
    60
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    46 / 914 (5.03%)
         occurrences all number
    47
    Neutrophil count decreased
         subjects affected / exposed
    58 / 914 (6.35%)
         occurrences all number
    96
    Weight decreased
         subjects affected / exposed
    50 / 914 (5.47%)
         occurrences all number
    51
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression
         subjects affected / exposed
    57 / 914 (6.24%)
         occurrences all number
    58
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    234 / 914 (25.60%)
         occurrences all number
    259
    Neutropenia
         subjects affected / exposed
    427 / 914 (46.72%)
         occurrences all number
    845
    Thrombocytopenia
         subjects affected / exposed
    65 / 914 (7.11%)
         occurrences all number
    76
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    171 / 914 (18.71%)
         occurrences all number
    215
    Pyrexia
         subjects affected / exposed
    73 / 914 (7.99%)
         occurrences all number
    84
    Fatigue
         subjects affected / exposed
    165 / 914 (18.05%)
         occurrences all number
    189
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    74 / 914 (8.10%)
         occurrences all number
    87
    Constipation
         subjects affected / exposed
    92 / 914 (10.07%)
         occurrences all number
    98
    Diarrhoea
         subjects affected / exposed
    218 / 914 (23.85%)
         occurrences all number
    290
    Nausea
         subjects affected / exposed
    268 / 914 (29.32%)
         occurrences all number
    367
    Vomiting
         subjects affected / exposed
    152 / 914 (16.63%)
         occurrences all number
    202
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    145 / 914 (15.86%)
         occurrences all number
    157

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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
    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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