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    Clinical Trial Results:
    An Open-Label Extension Study of the Long-Term Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (IPF)

    Summary
    EudraCT number
    2007-007800-13
    Trial protocol
    IE   GB   DE   FR   BE   ES   IT  
    Global end of trial date
    11 Feb 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    04 Mar 2017
    First version publication date
    04 Mar 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GA29960
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00662038
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Alternate study identifier: PIPF-012
    Sponsors
    Sponsor organisation name
    Hoffmann-La Roche
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Medical Communications, Hoffmann-La Roche, +1 800 8218590, genentech@druginfo.com
    Scientific contact
    Medical Communications, Hoffmann-La Roche, +1 800 8218590, genentech@druginfo.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
    17 Oct 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Feb 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Feb 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The trial objective was to obtain additional safety data for pirfenidone 2403 mg/d in subjects with idiopathic pulmonary fibrosis (IPF) who completed either Study PIPF-004 or PIPF-006.
    Protection of trial subjects
    Each subject, or the subject's representative, signed an informed consent form prior to screening.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    02 Sep 2008
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    90 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 759
    Country: Number of subjects enrolled
    Australia: 63
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Brazil: 24
    Country: Number of subjects enrolled
    Canada: 32
    Country: Number of subjects enrolled
    France: 10
    Country: Number of subjects enrolled
    Germany: 18
    Country: Number of subjects enrolled
    Israel: 15
    Country: Number of subjects enrolled
    Italy: 43
    Country: Number of subjects enrolled
    Mexico: 16
    Country: Number of subjects enrolled
    New Zealand: 3
    Country: Number of subjects enrolled
    Peru: 36
    Country: Number of subjects enrolled
    Poland: 9
    Country: Number of subjects enrolled
    Singapore: 1
    Country: Number of subjects enrolled
    Spain: 14
    Country: Number of subjects enrolled
    United Kingdom: 10
    Worldwide total number of subjects
    1058
    EEA total number of subjects
    109
    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)
    313
    From 65 to 84 years
    745
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 1058 subjects enrolled from Studies PIPF-004/006/016.

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

    Arms
    Arm title
    Pirfenidone
    Arm description
    Pirfenidone, 2403 mg/d, administered as 801-mg doses, three times daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Pirfenidone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Pirfenidone, 2403 milligrams per day (mg/d), administered as 801 mg doses, three times daily.

    Number of subjects in period 1
    Pirfenidone
    Started
    1058
    Completed
    427
    Not completed
    631
         Adverse event, serious fatal
    95
         Consent withdrawn by subject
    83
         Physician decision
    19
         Adverse event, non-fatal
    358
         Lung transplantation
    44
         Withdrawn consent
    22
         Reason not specified
    3
         Sponsor decision
    1
         Lost to follow-up
    1
         Continued treatment
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Pirfenidone
    Reporting group description
    Pirfenidone, 2403 mg/d, administered as 801-mg doses, three times daily.

    Reporting group values
    Pirfenidone Total
    Number of subjects
    1058 1058
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    313 313
        Elderly (From 65-84 years)
    745 745
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    68.5 ± 7.47 -
    Gender, Male/Female
    Units: Subjects
        Female
    268 268
        Male
    790 790

    End points

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    End points reporting groups
    Reporting group title
    Pirfenidone
    Reporting group description
    Pirfenidone, 2403 mg/d, administered as 801-mg doses, three times daily.

    Primary: Percentage of Subjects with Adverse Events

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    End point title
    Percentage of Subjects with Adverse Events [1]
    End point description
    An adverse event defined as any unfavorable, harmful, or pathologic change in a research subject administered a pharmaceutical study treatment as indicated by physical signs, symptoms, and/or clinically significant laboratory abnormalities that occurred during the treatment and the post-treatment period, regardless of suspected cause.
    End point type
    Primary
    End point timeframe
    7.5 years
    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: Descriptive analysis only.
    End point values
    Pirfenidone
    Number of subjects analysed
    1058
    Units: percentage of subjects
        number (not applicable)
    98
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    7.5 years
    Adverse event reporting additional description
    Adverse events were recorded at every contact with the participant.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    11.0
    Reporting groups
    Reporting group title
    Pirfenidone
    Reporting group description
    Pirfenidone, 2403 mg/d, administered as 801 mg doses, three times daily.

    Serious adverse events
    Pirfenidone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    571 / 1058 (53.97%)
         number of deaths (all causes)
    231
         number of deaths resulting from adverse events
    13
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma pancreas
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Benign ovarian tumour
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bladder cancer recurrent
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Breast cancer
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Breast cancer in situ
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Bronchial carcinoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Burkitt's lymphoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Colon cancer
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Colon cancer metastatic
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastric adenoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic neoplasm
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic neoplasm malignant
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal adenocarcinoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Large cell carcinoma of the respiratory tract stage unspecified
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Lung adenocarcinoma
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Lung adenocarcinoma Stage IV
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    6 / 1058 (0.57%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 3
    Lung neoplasm malignant
         subjects affected / exposed
    8 / 1058 (0.76%)
         occurrences causally related to treatment / all
    1 / 8
         deaths causally related to treatment / all
    1 / 3
    Lung squamous cell carcinoma stage unspecified
         subjects affected / exposed
    8 / 1058 (0.76%)
         occurrences causally related to treatment / all
    1 / 9
         deaths causally related to treatment / all
    0 / 1
    Lymphoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malignant melanoma Stage I
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malignant pleural effusion
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to bone
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Metastases to liver
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    5 / 1058 (0.47%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Non-small cell lung cancer metastatic
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Non-small cell lung cancer Stage IV
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Oesophageal adenocarcinoma metastatic
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Oesophageal cancer metastatic
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Ovarian cancer
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ovarian cancer recurrent
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Prostate cancer
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Prostate cancer metastatic
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Renal cancer
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sarcoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Small cell carcinoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Small cell lung cancer stage unspecified
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Air embolism
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Aortic aneurysm
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Aortic stenosis
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Arterial occlusive disease
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    7 / 1058 (0.66%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Hypertension
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Embolism venous
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypotension
         subjects affected / exposed
    7 / 1058 (0.66%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Shock
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vasculitis necrotising
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Chest pain
         subjects affected / exposed
    15 / 1058 (1.42%)
         occurrences causally related to treatment / all
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    Death
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Hypothermia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    6 / 1058 (0.57%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Anti-neutrophil cytoplasmic antibody positive vasculitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Polyarteritis nodosa
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Endometriosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endosalpingiosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Female genital tract fistula
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pelvic floor muscle weakness
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Prostatitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Acute respiratory failure
         subjects affected / exposed
    30 / 1058 (2.84%)
         occurrences causally related to treatment / all
    5 / 30
         deaths causally related to treatment / all
    2 / 11
    Alveolitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Cough
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    8 / 1058 (0.76%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Haemoptysis
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypoxia
         subjects affected / exposed
    17 / 1058 (1.61%)
         occurrences causally related to treatment / all
    1 / 18
         deaths causally related to treatment / all
    1 / 4
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    230 / 1058 (21.74%)
         occurrences causally related to treatment / all
    9 / 276
         deaths causally related to treatment / all
    2 / 133
    Increased bronchial secretion
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Lung disorder
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nasal discomfort
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleurisy
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pneumomediastinum
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    8 / 1058 (0.76%)
         occurrences causally related to treatment / all
    1 / 8
         deaths causally related to treatment / all
    0 / 1
    Pneumonitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumothorax
         subjects affected / exposed
    8 / 1058 (0.76%)
         occurrences causally related to treatment / all
    2 / 12
         deaths causally related to treatment / all
    0 / 0
    Pneumothorax spontaneous tension
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary arterial hypertension
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    19 / 1058 (1.80%)
         occurrences causally related to treatment / all
    3 / 20
         deaths causally related to treatment / all
    0 / 0
    Pulmonary cavitation
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    11 / 1058 (1.04%)
         occurrences causally related to treatment / all
    0 / 11
         deaths causally related to treatment / all
    0 / 2
    Pulmonary mass
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory failure
         subjects affected / exposed
    29 / 1058 (2.74%)
         occurrences causally related to treatment / all
    4 / 29
         deaths causally related to treatment / all
    1 / 18
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Depression
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Major depression
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Mycobacteria blood test positive
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Panel-reactive antibody increased
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pulmonary arterial pressure increased
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Troponin increased
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tumour marker increased
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Burns second degree
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device lead damage
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Drug toxicity
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Extradural haematoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Failure of implant
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fall
         subjects affected / exposed
    5 / 1058 (0.47%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fractured coccyx
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hip fracture
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Incisional hernia, obstructive
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Patella fracture
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Post procedural complication
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Radiation pneumonitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal haematoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal injury
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skeletal injury
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin laceration
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Spinal cord injury
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sternal fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Struck by lightning
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Congenital, familial and genetic disorders
    Gastrointestinal arteriovenous malformation
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    7 / 1058 (0.66%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    12 / 1058 (1.13%)
         occurrences causally related to treatment / all
    0 / 12
         deaths causally related to treatment / all
    0 / 1
    Acute right ventricular failure
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Angina pectoris
         subjects affected / exposed
    6 / 1058 (0.57%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Angina unstable
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Arrhythmia
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    Arteriosclerosis coronary artery
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    26 / 1058 (2.46%)
         occurrences causally related to treatment / all
    1 / 32
         deaths causally related to treatment / all
    0 / 1
    Atrial flutter
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Bradycardia
         subjects affected / exposed
    5 / 1058 (0.47%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    9 / 1058 (0.85%)
         occurrences causally related to treatment / all
    0 / 9
         deaths causally related to treatment / all
    0 / 6
    Cardiac failure
         subjects affected / exposed
    5 / 1058 (0.47%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    12 / 1058 (1.13%)
         occurrences causally related to treatment / all
    1 / 19
         deaths causally related to treatment / all
    1 / 2
    Cardiomyopathy
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    20 / 1058 (1.89%)
         occurrences causally related to treatment / all
    0 / 20
         deaths causally related to treatment / all
    0 / 0
    Coronary artery dissection
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Heart valve incompetence
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    7 / 1058 (0.66%)
         occurrences causally related to treatment / all
    1 / 7
         deaths causally related to treatment / all
    1 / 3
    Myocardial ischaemia
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Palpitations
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Right ventricular dysfunction
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Sick sinus syndrome
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Anoxic encephalopathy
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Brain stem infarction
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Central nervous system lesion
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cerebral thrombosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    14 / 1058 (1.32%)
         occurrences causally related to treatment / all
    3 / 16
         deaths causally related to treatment / all
    1 / 4
    Chronic inflammatory demyelinating polyradiculoneuropathy
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Convulsion
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Demyelinating polyneuropathy
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Embolic stroke
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hemiparesis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Mononeuropathy multiplex
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Paraparesis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Syncope
         subjects affected / exposed
    20 / 1058 (1.89%)
         occurrences causally related to treatment / all
    2 / 26
         deaths causally related to treatment / all
    0 / 0
    Syncope vasovagal
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tension headache
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thalamic infarction
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    8 / 1058 (0.76%)
         occurrences causally related to treatment / all
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 1058 (0.47%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Coagulopathy
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Vertigo positional
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Eye disorder
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Retinal detachment
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Colonic fistula
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Colonic polyp
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Diverticulum
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    5 / 1058 (0.47%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Inguinal hernia strangulated
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Intra-abdominal haematoma
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Jejunal perforation
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Mesenteric vein thrombosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Oesophageal perforation
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rectal polyp
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    Small intestinal perforation
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Umbilical hernia, obstructive
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Bile duct stenosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bile duct stone
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Biliary dyskinesia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholangitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cholecystitis
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypoaesthesia facial
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Photosensitivity reaction
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Urticaria
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Calculus ureteric
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Glomerulonephritis rapidly progressive
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haematuria
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    6 / 1058 (0.57%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Renal cyst
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal failure
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    Renal failure acute
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endocrine disorders
    Adrenal mass
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Costochondritis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Muscle spasms
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neck pain
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    7 / 1058 (0.66%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Osteoporosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Abscess intestinal
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Acute sinusitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bacteraemia
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Bacterial abscess central nervous system
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bartonellosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    32 / 1058 (3.02%)
         occurrences causally related to treatment / all
    0 / 38
         deaths causally related to treatment / all
    0 / 0
    Bronchitis viral
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bursitis infective
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Campylobacter intestinal infection
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Candidiasis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Cellulitis staphylococcal
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Clostridial infection
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diverticulitis
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endocarditis enterococcal
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fungal oesophagitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Herpes zoster oticus
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Influenza
         subjects affected / exposed
    7 / 1058 (0.66%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Liver abscess
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    1 / 1
    Lower respiratory tract infection
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Lower respiratory tract infection bacterial
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lung infection
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Lung infection pseudomonal
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumocystis jiroveci pneumonia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Pneumonia
         subjects affected / exposed
    90 / 1058 (8.51%)
         occurrences causally related to treatment / all
    7 / 104
         deaths causally related to treatment / all
    1 / 10
    Pneumonia bacterial
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pneumonia herpes viral
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pneumonia pneumococcal
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Postoperative abscess
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Septic shock
         subjects affected / exposed
    3 / 1058 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Sinusitis
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    8 / 1058 (0.76%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 1058 (0.09%)
         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 / 1058 (0.19%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Dehydration
         subjects affected / exposed
    6 / 1058 (0.57%)
         occurrences causally related to treatment / all
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypochloraemia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    2 / 1058 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    4 / 1058 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    1 / 1058 (0.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 1058 (0.09%)
         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
    Pirfenidone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1027 / 1058 (97.07%)
    Investigations
    Weight decreased
         subjects affected / exposed
    153 / 1058 (14.46%)
         occurrences all number
    173
    Vascular disorders
    Hypertension
         subjects affected / exposed
    71 / 1058 (6.71%)
         occurrences all number
    72
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    176 / 1058 (16.64%)
         occurrences all number
    225
    Headache
         subjects affected / exposed
    157 / 1058 (14.84%)
         occurrences all number
    248
    Syncope
         subjects affected / exposed
    55 / 1058 (5.20%)
         occurrences all number
    65
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    128 / 1058 (12.10%)
         occurrences all number
    159
    Fatigue
         subjects affected / exposed
    210 / 1058 (19.85%)
         occurrences all number
    251
    Asthenia
         subjects affected / exposed
    65 / 1058 (6.14%)
         occurrences all number
    72
    Chest pain
         subjects affected / exposed
    64 / 1058 (6.05%)
         occurrences all number
    76
    Pyrexia
         subjects affected / exposed
    60 / 1058 (5.67%)
         occurrences all number
    78
    Eye disorders
    Cataract
         subjects affected / exposed
    53 / 1058 (5.01%)
         occurrences all number
    67
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    60 / 1058 (5.67%)
         occurrences all number
    72
    Abdominal pain upper
         subjects affected / exposed
    66 / 1058 (6.24%)
         occurrences all number
    84
    Constipation
         subjects affected / exposed
    118 / 1058 (11.15%)
         occurrences all number
    142
    Gastrooesophageal reflux disease
         subjects affected / exposed
    102 / 1058 (9.64%)
         occurrences all number
    112
    Diarrhoea
         subjects affected / exposed
    242 / 1058 (22.87%)
         occurrences all number
    357
    Dyspepsia
         subjects affected / exposed
    126 / 1058 (11.91%)
         occurrences all number
    150
    Stomach discomfort
         subjects affected / exposed
    53 / 1058 (5.01%)
         occurrences all number
    73
    Vomiting
         subjects affected / exposed
    122 / 1058 (11.53%)
         occurrences all number
    172
    Nausea
         subjects affected / exposed
    305 / 1058 (28.83%)
         occurrences all number
    431
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    330 / 1058 (31.19%)
         occurrences all number
    435
    Dyspnoea exertional
         subjects affected / exposed
    68 / 1058 (6.43%)
         occurrences all number
    69
    Dyspnoea
         subjects affected / exposed
    325 / 1058 (30.72%)
         occurrences all number
    412
    Epistaxis
         subjects affected / exposed
    64 / 1058 (6.05%)
         occurrences all number
    84
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    221 / 1058 (20.89%)
         occurrences all number
    271
    Hypoxia
         subjects affected / exposed
    73 / 1058 (6.90%)
         occurrences all number
    79
    Productive cough
         subjects affected / exposed
    62 / 1058 (5.86%)
         occurrences all number
    75
    Pharyngolaryngeal pain
         subjects affected / exposed
    71 / 1058 (6.71%)
         occurrences all number
    86
    Nasal congestion
         subjects affected / exposed
    56 / 1058 (5.29%)
         occurrences all number
    64
    Pulmonary hypertension
         subjects affected / exposed
    123 / 1058 (11.63%)
         occurrences all number
    128
    Skin and subcutaneous tissue disorders
    Photosensitivity reaction
         subjects affected / exposed
    74 / 1058 (6.99%)
         occurrences all number
    98
    Pruritus
         subjects affected / exposed
    71 / 1058 (6.71%)
         occurrences all number
    82
    Rash
         subjects affected / exposed
    156 / 1058 (14.74%)
         occurrences all number
    230
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    84 / 1058 (7.94%)
         occurrences all number
    89
    Insomnia
         subjects affected / exposed
    111 / 1058 (10.49%)
         occurrences all number
    121
    Depression
         subjects affected / exposed
    82 / 1058 (7.75%)
         occurrences all number
    85
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    146 / 1058 (13.80%)
         occurrences all number
    178
    Arthralgia
         subjects affected / exposed
    89 / 1058 (8.41%)
         occurrences all number
    119
    Pain in extremity
         subjects affected / exposed
    67 / 1058 (6.33%)
         occurrences all number
    82
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    254 / 1058 (24.01%)
         occurrences all number
    447
    Influenza
         subjects affected / exposed
    75 / 1058 (7.09%)
         occurrences all number
    94
    Lower respiratory tract infection
         subjects affected / exposed
    67 / 1058 (6.33%)
         occurrences all number
    123
    Respiratory tract infection
         subjects affected / exposed
    57 / 1058 (5.39%)
         occurrences all number
    69
    Nasopharyngitis
         subjects affected / exposed
    202 / 1058 (19.09%)
         occurrences all number
    359
    Pneumonia
         subjects affected / exposed
    88 / 1058 (8.32%)
         occurrences all number
    107
    Urinary tract infection
         subjects affected / exposed
    103 / 1058 (9.74%)
         occurrences all number
    190
    Upper respiratory tract infection
         subjects affected / exposed
    295 / 1058 (27.88%)
         occurrences all number
    522
    Sinusitis
         subjects affected / exposed
    130 / 1058 (12.29%)
         occurrences all number
    218
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    120 / 1058 (11.34%)
         occurrences all number
    136
    Decreased appetite
         subjects affected / exposed
    95 / 1058 (8.98%)
         occurrences all number
    103

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Sep 2010
    Revised duration of treatment period; clarified dose escalation for subjects who required dose reduction while participating in Study PIPF-004; clarified exclusion criteria for QT corrected for heart rate using Bazett's method (QTcB); incorporated updated background information; revised windows for post-treatment follow-up visit and collection of concomitant medications; revised requirements for early withdrawal from study visit; corrected required visits for subjects who required restart visits.
    07 Oct 2011
    Allowed subjects from additional qualifying InterMune clinical studies to enroll (previously limited to subjects from Studies PIPF-004/006); eliminated efficacy assessments as of 15 May 2012; simplified and clarified the safety assessments as of 15 May 2012, as follows: revised prohibited prior and concomitant medications; eliminated exclusion criteria related to liver tests and electrocardiogram (ECG) results; eliminated subject diary; clarified dose-escalation guidelines, and revised dose-modification, interruption, and restart guidelines; clarified requirements for pre-restart and restart visits; updated adverse event reporting guidelines.

    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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