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    Clinical Trial Results:
    An Open-Label Study of Abiraterone Acetate in Subjects with Metastatic Castration- Resistant Prostate Cancer Who Have Progressed After Taxane-Based Chemotherapy

    Summary
    EudraCT number
    2010-021425-13
    Trial protocol
    CZ   HU   ES   IT   LT   DK   GR  
    Global end of trial date
    19 Oct 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    23 Sep 2016
    First version publication date
    23 Sep 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    212082PCR3001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01217697
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Janssen Research and Development, LLC
    Sponsor organisation address
    Antwerpseweg 15-17, Beerse, Belgium, B-2340
    Public contact
    Clinical Registry Group, Janssen Research and Development, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Research and Development, ClinicalTrialsEU@its.jnj.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
    19 Oct 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Oct 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study was to collect additional safety data during treatment with abiraterone acetate plus prednisone or prednisolone among subjects with metastatic castration-resistant prostate cancer (CRPC) who had failed 1 or 2 chemotherapy regimens, 1 of which contains a taxane base such as docetaxel, who reside in areas in which abiraterone acetate was not yet available through local healthcare providers,and who were not eligible for enrollment into an available ongoing clinical study of abiraterone acetate.
    Protection of trial subjects
    Safety evaluations included the collection of adverse events, evaluation of deaths, other serious adverse events and other significant adverse events, clinical laboratory tests, other safety observations (vital signs, physical examinations and Electrocardiograms).
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    17 Nov 2010
    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: 312
    Country: Number of subjects enrolled
    Brazil: 73
    Country: Number of subjects enrolled
    Canada: 100
    Country: Number of subjects enrolled
    Colombia: 2
    Country: Number of subjects enrolled
    Czech Republic: 107
    Country: Number of subjects enrolled
    Denmark: 57
    Country: Number of subjects enrolled
    Spain: 96
    Country: Number of subjects enrolled
    Greece: 61
    Country: Number of subjects enrolled
    Hong Kong: 17
    Country: Number of subjects enrolled
    Croatia: 20
    Country: Number of subjects enrolled
    Hungary: 84
    Country: Number of subjects enrolled
    Indonesia: 2
    Country: Number of subjects enrolled
    Italy: 550
    Country: Number of subjects enrolled
    Korea, Republic of: 45
    Country: Number of subjects enrolled
    Mexico: 63
    Country: Number of subjects enrolled
    Malaysia: 17
    Country: Number of subjects enrolled
    Poland: 50
    Country: Number of subjects enrolled
    Romania: 60
    Country: Number of subjects enrolled
    Russian Federation: 86
    Country: Number of subjects enrolled
    Singapore: 33
    Country: Number of subjects enrolled
    Thailand: 26
    Country: Number of subjects enrolled
    Taiwan: 23
    Country: Number of subjects enrolled
    United States: 432
    Worldwide total number of subjects
    2316
    EEA total number of subjects
    1085
    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)
    595
    From 65 to 84 years
    1667
    85 years and over
    54

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted from 17 November 2010 to 19 October 2015.

    Pre-assignment
    Screening details
    2,316 Subjects were enrolled in the study.

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

    Arms
    Arm title
    Abiraterone Acetate
    Arm description
    Subjects received abiraterone acetate 1000 milligram (mg) daily as four tablets of 250 mg orally and 5 mg prednisone or prednisolone twice daily as oral dose.
    Arm type
    Experimental

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received prednisone 5 mg twice daily as oral tablet OR prednisolone 5 mg (if prednisone is not available).

    Investigational medicinal product name
    Abiraterone Acetate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received abiraterone acetate 1000 milligram (mg) daily as four tablets of 250 mg orally

    Number of subjects in period 1
    Abiraterone Acetate
    Started
    2316
    Completed
    0
    Not completed
    2316
         Protocol deviation
    16
         Death
    178
         Disease Progression
    1142
         Other
    109
         Study Terminated by sponsor
    59
         Market Authorization / Reimbursement
    455
         Consent withdrawn by subject
    153
         Adverse Event
    186
         Lost to follow-up
    18

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Abiraterone Acetate
    Reporting group description
    Subjects received abiraterone acetate 1000 milligram (mg) daily as four tablets of 250 mg orally and 5 mg prednisone or prednisolone twice daily as oral dose.

    Reporting group values
    Abiraterone Acetate Total
    Number of subjects
    2316 2316
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    595 595
        From 65 to 84 years
    1667 1667
        85 years and over
    54 54
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    70 ± 8.07 -
    Title for Gender
    Units: subjects
        Male
    2316 2316

    End points

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    End points reporting groups
    Reporting group title
    Abiraterone Acetate
    Reporting group description
    Subjects received abiraterone acetate 1000 milligram (mg) daily as four tablets of 250 mg orally and 5 mg prednisone or prednisolone twice daily as oral dose.

    Subject analysis set title
    Safety Analysis Population
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Saefty analysis set included all subjects who received at least one dose of primary study drug (Abiraterone acetate)

    Primary: Number of Subjects With Adverse Events (A.Es)

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    End point title
    Number of Subjects With Adverse Events (A.Es) [1]
    End point description
    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
    End point type
    Primary
    End point timeframe
    From the time of signing the informed consent to the time of the End-of-Study Visit (30 days after discontinuation of study drug)
    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: Statistical analysis was not reported for this endpoint as inferential analysis was not performed as planned.
    End point values
    Abiraterone Acetate
    Number of subjects analysed
    2316 [2]
    Units: Subjects
        Treatment-emergent serious or clinically important
    1166
        Grade 3-4 treatment emergent A.Es
    980
        Treatment-emergent serious A.Es
    682
        Treatment-emergent A.Es leading to treatment
    385
        Treatment-emergent A.Es leading to death
    248
    Notes
    [2] - Safety analysis population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the time of signing the informed consent to the time of the End-of-Study Visit (30 days after discontinuation of study drug)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    14.0
    Reporting groups
    Reporting group title
    Abiraterone Acetate
    Reporting group description
    Subjects received abiraterone acetate 1000 milligram (mg) daily as four tablets of 250 mg orally and 5 mg prednisone or prednisolone twice daily as oral dose.

    Serious adverse events
    Abiraterone Acetate
    Total subjects affected by serious adverse events
         subjects affected / exposed
    818 / 2316 (35.32%)
         number of deaths (all causes)
    248
         number of deaths resulting from adverse events
    Vascular disorders
    Arterial Occlusive Disease
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Circulatory Collapse
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Deep Vein Thrombosis
         subjects affected / exposed
    8 / 2316 (0.35%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Haematoma
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhage
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Hypertension
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypotension
         subjects affected / exposed
    8 / 2316 (0.35%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 2
    Peripheral Ischaemia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular Compression
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Shock
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Venous Thrombosis Limb
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Surgical and medical procedures
    Aortic Valve Replacement
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coronary Angioplasty
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fasciectomy
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hernia Repair
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hospitalisation
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Photon Radiation Therapy to Brain
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung Lobectomy
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Radiotherapy
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal Decompression
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal Fusion Surgery
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Stent Removal
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer Pain
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Basal Cell Carcinoma
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Carcinoid Tumour of the Caecum
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastric Cancer
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Colon Cancer
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Lung Adenocarcinoma
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung Neoplasm Malignant
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malignant Melanoma
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Malignant Pleural Effusion
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Meningeal Neoplasm
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to Bone Marrow
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Metastases to Bone
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to Central Nervous System
         subjects affected / exposed
    6 / 2316 (0.26%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    Metastases to Lung
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Metastases to Liver
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Metastatic Pain
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Metastases to Meninges
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Neoplasm Malignant
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Pancreatic Carcinoma
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pancreatic Neoplasm
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Prostate Cancer
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 4
    Prostate Cancer Metastatic
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    Rectal Cancer
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tumour Flare
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tumour Pain
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    15 / 2316 (0.65%)
         occurrences causally related to treatment / all
    0 / 15
         deaths causally related to treatment / all
    0 / 4
    Chest Discomfort
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Chest Pain
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    Death
         subjects affected / exposed
    12 / 2316 (0.52%)
         occurrences causally related to treatment / all
    0 / 12
         deaths causally related to treatment / all
    0 / 12
    Device Failure
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Discomfort
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Disease Progression
         subjects affected / exposed
    25 / 2316 (1.08%)
         occurrences causally related to treatment / all
    0 / 25
         deaths causally related to treatment / all
    0 / 22
    Drug Interaction
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fatigue
         subjects affected / exposed
    15 / 2316 (0.65%)
         occurrences causally related to treatment / all
    0 / 16
         deaths causally related to treatment / all
    0 / 4
    General Physical Health Deterioration
         subjects affected / exposed
    39 / 2316 (1.68%)
         occurrences causally related to treatment / all
    0 / 40
         deaths causally related to treatment / all
    0 / 31
    Hernia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperpyrexia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Malaise
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Multi-Organ Failure
         subjects affected / exposed
    9 / 2316 (0.39%)
         occurrences causally related to treatment / all
    0 / 9
         deaths causally related to treatment / all
    0 / 9
    Medical Device Complication
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Oedema
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Oedema Peripheral
         subjects affected / exposed
    10 / 2316 (0.43%)
         occurrences causally related to treatment / all
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    Pain
         subjects affected / exposed
    20 / 2316 (0.86%)
         occurrences causally related to treatment / all
    0 / 22
         deaths causally related to treatment / all
    0 / 1
    Performance Status Decreased
         subjects affected / exposed
    6 / 2316 (0.26%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 6
    Sudden Death
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Pyrexia
         subjects affected / exposed
    21 / 2316 (0.91%)
         occurrences causally related to treatment / all
    0 / 29
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Confusional State
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Delirium
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Depression
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Disorientation
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Mental Status Changes
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hallucination
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Suicidal Ideation
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Suicide Attempt
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Breast Pain
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Prostatic Obstruction
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Accident
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Accidental Overdose
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Cervical Vertebral Fracture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ankle Fracture
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Clavicle Fracture
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Compression Fracture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cystitis Radiation
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fall
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Femoral Neck Fracture
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Femur Fracture
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    Foot Fracture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fracture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hand Fracture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Head Injury
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Humerus Fracture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lumbar Vertebral Fracture
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Open Wound
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Overdose
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Patella Fracture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pelvic Fracture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Post Procedural Haematuria
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Radius Fracture
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Rib Fracture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal Compression Fracture
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Spinal Fracture
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Subdural Haematoma
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    Subdural Haemorrhage
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Thoracic Vertebral Fracture
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Toxicity to Various Agents
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Transfusion Reaction
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Traumatic Brain Injury
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper Limb Fracture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Wound Secretion
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Biopsy Liver
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood Creatinine Increased
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Haemoglobin Decreased
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic Enzyme Increased
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    International Normalised Ratio Increased
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Liver Function Test Abnormal
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Platelet Count Decreased
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Prostatic Specific Antigen Increased
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urine Output Decreased
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Acute Coronary Syndrome
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 3
    Angina Pectoris
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Acute Myocardial Infarction
         subjects affected / exposed
    6 / 2316 (0.26%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Angina Unstable
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Atrial Fibrillation
         subjects affected / exposed
    8 / 2316 (0.35%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Atrial Flutter
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Atrioventricular Block
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bundle Branch Block Left
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac Arrest
         subjects affected / exposed
    8 / 2316 (0.35%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 8
    Cardiac Disorder
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac Failure Congestive
         subjects affected / exposed
    6 / 2316 (0.26%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 4
    Cardio-Respiratory Arrest
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 4
    Cardiac Failure
         subjects affected / exposed
    9 / 2316 (0.39%)
         occurrences causally related to treatment / all
    0 / 9
         deaths causally related to treatment / all
    0 / 4
    Cardio-Respiratory Distress
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cardiovascular Disorder
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Myocardial Infarction
         subjects affected / exposed
    6 / 2316 (0.26%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    Intracardiac Thrombus
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Myocardial Ischaemia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Palpitations
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pericardial Effusion
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Supraventricular Tachycardia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ventricular Tachycardia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute Interstitial Pneumonitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Acute Respiratory Failure
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Cough
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    15 / 2316 (0.65%)
         occurrences causally related to treatment / all
    0 / 17
         deaths causally related to treatment / all
    0 / 2
    Epistaxis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Interstitial Lung Disease
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hydrothorax
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Laryngeal Oedema
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung Disorder
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pleural Effusion
         subjects affected / exposed
    9 / 2316 (0.39%)
         occurrences causally related to treatment / all
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    Pneumonia Aspiration
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pulmonary Congestion
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    12 / 2316 (0.52%)
         occurrences causally related to treatment / all
    0 / 12
         deaths causally related to treatment / all
    0 / 2
    Pulmonary Microemboli
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary Oedema
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Respiratory Arrest
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Respiratory Disorder
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory Failure
         subjects affected / exposed
    10 / 2316 (0.43%)
         occurrences causally related to treatment / all
    0 / 10
         deaths causally related to treatment / all
    0 / 10
    Blood and lymphatic system disorders
    Anaemia Macrocytic
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Anaemia
    alternative assessment type: Systematic
         subjects affected / exposed
    50 / 2316 (2.16%)
         occurrences causally related to treatment / all
    0 / 53
         deaths causally related to treatment / all
    0 / 12
    Bone Marrow Failure
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Disseminated Intravascular Coagulation
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    Febrile Neutropenia
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Leukopenia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancytopenia
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Thrombocytopenia
         subjects affected / exposed
    8 / 2316 (0.35%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    Neutropenia
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Thrombotic Thrombocytopenic Purpura
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Nervous system disorders
    Altered State of Consciousness
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Brain Oedema
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Central Nervous System Lesion
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cerebral Haemorrhage
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Cerebral Infarction
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cerebral Ischaemia
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Cerebrovascular Accident
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 5
    Cognitive Disorder
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Coma
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Convulsion
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cranial Nerve Disorder
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Depressed Level of Consciousness
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Diabetic Coma
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diabetic Neuropathy
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dizziness
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Dysarthria
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Epilepsy
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Haemorrhage Intracranial
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Hemiparesis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Headache
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Hemiplegia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Iiird Nerve Paralysis
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Lethargy
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Loss of Consciousness
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolic Encephalopathy
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Nerve Root Compression
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Monoparesis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neuralgia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neurological Symptom
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Paraparesis
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    Paraplegia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Peripheral Sensory Neuropathy
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sedation
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal Cord Compression
         subjects affected / exposed
    28 / 2316 (1.21%)
         occurrences causally related to treatment / all
    0 / 28
         deaths causally related to treatment / all
    0 / 2
    Syncope
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Trigeminal Neuralgia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Transient Ischaemic Attack
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Glaucoma
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diplopia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Visual Impairment
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Retinal Vein Occlusion
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ear and labyrinth disorders
    Vertigo Positional
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vertigo
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal Adhesions
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal Distension
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Abdominal Mass
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal Pain
         subjects affected / exposed
    9 / 2316 (0.39%)
         occurrences causally related to treatment / all
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    Abdominal Pain Upper
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Anal Fistula
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Anal Haemorrhage
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ascites
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Colonic Obstruction
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Colitis
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Constipation
         subjects affected / exposed
    7 / 2316 (0.30%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    Diarrhoea
         subjects affected / exposed
    11 / 2316 (0.47%)
         occurrences causally related to treatment / all
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    Diverticulum
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diverticulum Intestinal Haemorrhagic
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Duodenal Ulcer
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Erosive Oesophagitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterovesical Fistula
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal Hypomotility
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal Haemorrhage
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Haematemesis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gingivitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hiatus Hernia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ileus
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Impaired Gastric Emptying
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal Obstruction
         subjects affected / exposed
    7 / 2316 (0.30%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    Large Intestine Perforation
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Lower Gastrointestinal Haemorrhage
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Nausea
         subjects affected / exposed
    7 / 2316 (0.30%)
         occurrences causally related to treatment / all
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    Mouth Haemorrhage
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Proctalgia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Obstruction Gastric
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rectal Haemorrhage
         subjects affected / exposed
    6 / 2316 (0.26%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    Retroperitoneal Haemorrhage
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    13 / 2316 (0.56%)
         occurrences causally related to treatment / all
    0 / 20
         deaths causally related to treatment / all
    0 / 0
    Small Intestinal Obstruction
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Upper Gastrointestinal Haemorrhage
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Renal and urinary disorders
    Bladder Obstruction
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dysuria
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Bladder Spasm
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haematuria
         subjects affected / exposed
    30 / 2316 (1.30%)
         occurrences causally related to treatment / all
    0 / 41
         deaths causally related to treatment / all
    0 / 2
    Hydronephrosis
         subjects affected / exposed
    10 / 2316 (0.43%)
         occurrences causally related to treatment / all
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    Nephrolithiasis
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Nephropathy Toxic
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Obstructive Uropathy
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Renal Failure
         subjects affected / exposed
    7 / 2316 (0.30%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    Renal Impairment
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Renal Failure Acute
         subjects affected / exposed
    16 / 2316 (0.69%)
         occurrences causally related to treatment / all
    0 / 16
         deaths causally related to treatment / all
    0 / 5
    Ureteric Rupture
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urethral Stenosis
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Urinary Incontinence
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary Retention
         subjects affected / exposed
    12 / 2316 (0.52%)
         occurrences causally related to treatment / all
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    Urinary Tract Obstruction
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholecystitis Acute
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cholecystitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic Function Abnormal
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic Failure
         subjects affected / exposed
    6 / 2316 (0.26%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 4
    Hepatitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatorenal Failure
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Liver Injury
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    13 / 2316 (0.56%)
         occurrences causally related to treatment / all
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    Back Pain
         subjects affected / exposed
    52 / 2316 (2.25%)
         occurrences causally related to treatment / all
    0 / 58
         deaths causally related to treatment / all
    0 / 3
    Bone Pain
         subjects affected / exposed
    16 / 2316 (0.69%)
         occurrences causally related to treatment / all
    0 / 16
         deaths causally related to treatment / all
    0 / 3
    Bursitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Groin Pain
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lumbar Spinal Stenosis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Muscle Spasms
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Muscular Weakness
         subjects affected / exposed
    7 / 2316 (0.30%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal Chest Pain
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal Pain
         subjects affected / exposed
    8 / 2316 (0.35%)
         occurrences causally related to treatment / all
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neck Pain
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteonecrosis of Jaw
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pain in Extremity
         subjects affected / exposed
    7 / 2316 (0.30%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Pathological Fracture
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Rhabdomyolysis
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Endocrine disorders
    Adrenal Insufficiency
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Decreased Appetite
         subjects affected / exposed
    5 / 2316 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Dehydration
         subjects affected / exposed
    18 / 2316 (0.78%)
         occurrences causally related to treatment / all
    0 / 19
         deaths causally related to treatment / all
    0 / 2
    Diabetes Mellitus
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diabetes Mellitus Inadequate Control
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Failure to Thrive
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Fluid Retention
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    7 / 2316 (0.30%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Abdominal Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Abscess Limb
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Alveolar Osteitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Anal Abscess
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Appendicitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous Fistula Site Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arthritis Infective
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Bacterial Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Biliary Sepsis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Biliary Tract Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Cellulitis Orbital
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Clostridium Difficile Colitis
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Device Related Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diverticulitis
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Enterocolitis Infectious
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia Bacteraemia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia Sepsis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Gastroenteritis Viral
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haematoma Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infection
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Infective Exacerbation of Chronic Obstructive Airways Disease
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Influenza
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Laryngitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lobar Pneumonia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower Respiratory Tract Infection
         subjects affected / exposed
    6 / 2316 (0.26%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Ludwig Angina
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Necrotising Fasciitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Post Procedural Sepsis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    40 / 2316 (1.73%)
         occurrences causally related to treatment / all
    0 / 44
         deaths causally related to treatment / all
    0 / 8
    Psoas Abscess
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pulmonary Tuberculosis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    2 / 2316 (0.09%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis Acute
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Salmonella Bacteraemia
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory Tract Infection
         subjects affected / exposed
    4 / 2316 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Salmonella Sepsis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Salmonellosis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Scrotal Abscess
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    18 / 2316 (0.78%)
         occurrences causally related to treatment / all
    0 / 18
         deaths causally related to treatment / all
    0 / 9
    Septic Shock
         subjects affected / exposed
    3 / 2316 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Staphylococcal Sepsis
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    34 / 2316 (1.47%)
         occurrences causally related to treatment / all
    0 / 38
         deaths causally related to treatment / all
    0 / 2
    Urinary Tract Infection Bacterial
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urosepsis
         subjects affected / exposed
    25 / 2316 (1.08%)
         occurrences causally related to treatment / all
    0 / 31
         deaths causally related to treatment / all
    0 / 3
    Viral Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 2316 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Wound Sepsis
         subjects affected / exposed
    1 / 2316 (0.04%)
         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
    Abiraterone Acetate
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    149 / 2316 (6.43%)
    Investigations
    Blood Alkaline Phosphatase Increased
    alternative assessment type: Systematic
         subjects affected / exposed
    149 / 2316 (6.43%)
         occurrences all number
    172

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Sep 2010
    Amendment clarified disease progression assessments in addition to other minor clarifications and corrections: Prostate-specific antigen (PSA) progression and clinical progression assessments were clarified, Key results from Study COU-AA-301 were summarized and included in the study design rationale as background for this early access protocol (EAP), Per the request from the United States (US) Food and Drug Administration, an exclusion criterion for prior systemic treatment with an azole drug, For example (e.g.), fluconazole, itraconazole, ketoconazole) within 1 month of study start was added. This was included because the safety of subjects with recent exposure to azoles and abiraterone had not been tested. Quality-of-Life (QoL) and medical resource utilization (MRU) assessments were expanded to be performed at non-European as well as European sites.
    20 May 2011
    Amendment added the following information in addition to the correction of minor errors: The end-of-study definition was revised with further clarification of the last assessment of the last subject. The dosage of abiraterone acetate was clarified to be once daily and not in divided doses Over the course of the day. References to sites in Europe for Patient-reported outcome/Medical resource utilization (PRO/MRU) assessments were removed as they may also be assessed at non-European sites. An attachment was added to clearly define PSA progression, to determine the eligibility of a subject for the study (referred to in the inclusion criteria). Concomitant therapy was added as an exclusion criterion. Location of recording clinically important signs and symptoms in the case report form (CRF) was specified. Clarification was made to inclusion criterion. Albumin was added to the serum chemistry panel to be consistent with other sections of the protocol. The definition of a serious adverse event (SAE) was updated, and the timeframe for case report form transmission to the sponsor was changed per company standards. Assessment of physical examination and measurement of blood pressure and weight were added to the CRF. Information on management of Grade 2 hypokalemia was added.
    07 May 2012
    Amendment added the following information in addition to the corrections of minor errors: Language for the reporting of all clinically important adverse events (AEs) to the sponsor was changed back to the wording in the original protocol. The timeframe for obtaining an electrocardiogram (ECG) in the screening period was changed to be consistent with the requirement associated with multiple gated acquisition (MUGA) scans. Assessment of serum testosterone level at screening was expanded to account for those areas where it was not the standard of care. The requirement for completion of the MRU questionnaire at Cycle 1 Day 1 was removed. An allowance for all study procedures to be conducted within a window of ± 2 days was added. Serum, magnesium, amylase, and lipase were added to the procedures required at the end of study visit. The term “investigator” was removed from “investigator prescribed” when referring to prednisone. The definition of uncontrolled hypertension in the exclusion criteria was clarified. Other azole drugs were added to list of prohibited medications. The upper limit of Grade 1 and the lower limit of Grade 2 increases in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) were amended from 2.5 x the upper limit of normal (ULN) to 3x ULN.

    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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