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    Clinical Trial Results:
    The H10 EORTC/GELA/IIL randomized Intergroup trial on early FDG-PET scan guided treatment adaptation versus standard combined modality treatment in patients with supradiaphragmatic stage I/II Hodgkin's lymphoma.

    Summary
    EudraCT number
    2005-002765-37
    Trial protocol
    NL   BE   DK   FR   IT   SK  
    Global end of trial date
    09 Jan 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    10 Aug 2016
    First version publication date
    10 Aug 2016
    Other versions
    Summary report(s)
    Trial design

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    20051
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00433433
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    European Organisation for Research and Treatment of Cancer
    Sponsor organisation address
    Avenue E. Mounier 83/11, Brussels, Belgium, 1200
    Public contact
    Project, Budget and Regulatory Dept, European Organisation for Research and Treatment of Cancer, +32 27441062, regulatory@eortc.be
    Scientific contact
    Project, Budget and Regulatory Dept, European Organisation for Research and Treatment of Cancer, +32 27441062, regulatory@eortc.be
    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
    09 Jan 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Jun 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Jan 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to evaluate whether chemotherapy alone is as effective -but less toxic-, as combined modality treatment in terms of progression-free survival (PFS), in patients with stages I/II Hodgkin’s lymphoma who are FDG-PET scan negative after two cycles of ABVD. This question will be addressed in the group of patients with favorable stages I/II disease as well as in those with unfavorable stages I/II disease. A secondary objective is to evaluate whether early change of chemotherapy from ABVD to escalated BEACOPP improves the progression-free survival of patients who are FDG-PET-positive after two cycles of ABVD, as compared with those who continue on standard ABVD in both favorable as well as unfavorable subsets of patients.
    Protection of trial subjects
    The responsible investigator has ensured that this study has been conducted in agreement with either the Declaration of Helsinki (Tokyo, Venice, Hong Kong, Somerset West and Edinburgh amendments) and/or the laws and regulations of the country, whichever provides the greatest protection of the patient. The protocol has been written, and the study has been conducted according to the ICH Harmonized Tripartite Guideline on Good Clinical Practice (ICH-GCP). The protocol has been approved by the competent ethics committee(s) as required by the applicable national legislation.
    Background therapy
    All randomized patients (standard and experimental arms), in both trial subsets (Favorable and Unfavorable), will be administered two cycles of ABVD (Doxorubicin 25 mg/m2 i.v., Bleomycin 10 mg/m2 i.v./i.m., Vinblastine 6 mg/m2 i.v., Dacarbazine 375 mg/m2 i.v. at day 1 and 15 of each cycle) and will subsequently have a FDG-PET scan, together with a conventional restaging (chest X-ray and CT-thorax).
    Evidence for comparator
    Standard treatment for patients with early stage Hodgkin lymphoma, with favorable or unfavorable prognosis, consists of chemotherapy (mainly ABVD) followed by radiotherapy. Fermé C, Eghbali H, Meerwaldt JH, et al: Chemotherapy plus involved-field radiation in early stage Hodgkin’s disease. N Engl J Med 357:1916-1927, 2007 Engert A, Plutschow A, Eich HT, et al: Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med 363:640-652, 2010
    Actual start date of recruitment
    23 Nov 2006
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy, Scientific research
    Long term follow-up duration
    20 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Slovakia: 15
    Country: Number of subjects enrolled
    Switzerland: 13
    Country: Number of subjects enrolled
    Belgium: 162
    Country: Number of subjects enrolled
    Croatia: 20
    Country: Number of subjects enrolled
    Denmark: 31
    Country: Number of subjects enrolled
    France: 970
    Country: Number of subjects enrolled
    Italy: 407
    Country: Number of subjects enrolled
    Netherlands: 332
    Worldwide total number of subjects
    1950
    EEA total number of subjects
    1937
    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)
    73
    Adults (18-64 years)
    1843
    From 65 to 84 years
    34
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    A total of 1950 patients were randomized between 23rd November 2006 and 22nd June 2011 in 158 institutions from 8 countries. Two additional patients were randomized but no informed consent was found (patients 62, 1192); these two patients are thus not reported.

    Pre-assignment
    Screening details
    Histologically confirmed Hodgkin's lymphoma (HL), except for nodular, lymphocyte predominant subtype (nodular paragranuloma) Supradiaphragmatic Ann Arbor clinical stage I or II Previously untreated Age 15-70 years WHO performance 0-3 FDG-PET scan prospectively planned after two cycles of ABVD in all patients Informed consent

    Period 1
    Period 1 title
    Randomization
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Favorable - Standard
    Arm description
    ABVD x 2 cycles (28 days each cycle)
    Arm type
    Active comparator

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Arm title
    Favorable - Experimental
    Arm description
    ABVD x 2 cycles (28 days each cycle)
    Arm type
    Experimental

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Arm title
    Unfavorable - Standard
    Arm description
    ABVD x 2 cycles (28 days each cycle)
    Arm type
    Active comparator

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Arm title
    Unfavorable - Experimental
    Arm description
    ABVD x 2 cycles (28 days each cycle)
    Arm type
    Experimental

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Number of subjects in period 1
    Favorable - Standard Favorable - Experimental Unfavorable - Standard Unfavorable - Experimental
    Started
    375
    379
    597
    599
    Completed
    371
    376
    583
    595
    Not completed
    4
    3
    14
    4
         Protocol deviation
    4
    3
    7
    2
         Physician decision
    -
    -
    3
    -
         Adverse event, serious fatal
    -
    -
    1
    1
         Adverse event, non-fatal
    -
    -
    1
    -
         Lost to follow-up
    -
    -
    2
    1
    Period 2
    Period 2 title
    PET after 2 cycles ABVD
    Is this the baseline period?
    Yes [1]
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Favorable - Standard - PET negative
    Arm description
    ABVD x 1 cycle (28 days) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions)
    Arm type
    Active comparator

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Arm title
    Favorable - Experimental - PET negative
    Arm description
    ABVD x 2 cycles (28 days each cycle) without further RT
    Arm type
    Experimental

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Arm title
    Unfavorable - Standard - PET negative
    Arm description
    ABVDx2 cycles (28 days each cycle)+ IN-RT 30Gy (+boost 6Gy to residual lesions).
    Arm type
    Active comparator

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Arm title
    Unfavorable - Experimental - PET negative
    Arm description
    ABVDx 4 cycles (28 days each cycle), without RT
    Arm type
    Experimental

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Arm title
    Standard - PET positive
    Arm description
    Favorable : ABVDx1 cycles (28 days each cycle) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions) Unfavorable: ABVDx2 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions).
    Arm type
    Active comparator

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Arm title
    Experimental - PET positive
    Arm description
    escalated BEACOPP x 2 cycles (21 days each cycle) + INRT30Gy (+boost 6Gy to residual lesions).
    Arm type
    Experimental

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cyclophosphamide 1250 mg/m2 i.v. day 1

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 35 mg/m2 i.v. day 1

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vincristine 1.4 mg/m2 i.v.(max.2mg) day 8

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 8

    Investigational medicinal product name
    Etoposide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Etoposide 200 mg/m2 i.v. day 1 to 3

    Investigational medicinal product name
    Procacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Procarbazine 100 mg/m2 orally day 1 to 7

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Prednisone 40 mg/m2 orally day 1 to 14

    Arm title
    Favorable - PET negative (after amendment 2010)
    Arm description
    ABVD x 1 cycle (28 days) + IN-RT 30GY (+boost 6GY to residual lesions).
    Arm type
    Not for comparison

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Arm title
    Unfavorable - PET negative (after amendment 2010)
    Arm description
    ABVD x 2 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions).
    Arm type
    Not for comparison

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 25 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Bleomycin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15

    Investigational medicinal product name
    Vinblastine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vinblastine 6 mg/m2 i.v. day 1 and 15

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine 375 mg/m2 i.v. day 1 and 15

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: Period 1 is the period starting at randomization and covers the two first cycles of ABVD. The 3 groups of interest (1) Favorable - PET negative 2) Unfavorable - PET negative 3) PET positive) can only be defined after the PET performed after 2 cycles ABVD, that is, at period 2.
    Number of subjects in period 2 [2]
    Favorable - Standard - PET negative Favorable - Experimental - PET negative Unfavorable - Standard - PET negative Unfavorable - Experimental - PET negative Standard - PET positive Experimental - PET positive Favorable - PET negative (after amendment 2010) Unfavorable - PET negative (after amendment 2010)
    Started
    227
    238
    292
    302
    192
    169
    185
    320
    Completed
    220
    228
    276
    284
    164
    139
    179
    309
    Not completed
    7
    10
    16
    18
    28
    30
    6
    11
         Protocol deviation
    1
    1
    3
    -
    1
    2
    -
    -
         Patient move
    1
    -
    -
    -
    -
    -
    -
    -
         Physician decision
    3
    6
    5
    8
    13
    18
    2
    6
         Lack of efficacy
    -
    -
    1
    -
    12
    -
    -
    1
         Adverse event, serious fatal
    -
    -
    -
    1
    -
    -
    -
    -
         Adverse event, non-fatal
    -
    1
    1
    4
    -
    -
    2
    2
         Patient refusal
    1
    2
    5
    5
    2
    10
    -
    2
         Unknown reason
    1
    -
    1
    -
    -
    -
    2
    -
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Of the total 1950 randomized patients, 4 patients did not start ABVD treatment or no information, 7 patients did not complete the 2 first ABVD cycles and 14 patients completed these 2 ABVD cycles but did not do the subsequent PET scan, thus leaving 1925 patients classified in the 3 groups of interest: 1) Favorable - PET negative 2) Unfavorable - PET negative 3) PET positive. 21 of these patients are included in the adverse events section as they received the background therapy (2 cycles ABVD).

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Favorable - Standard - PET negative
    Reporting group description
    ABVD x 1 cycle (28 days) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions)

    Reporting group title
    Favorable - Experimental - PET negative
    Reporting group description
    ABVD x 2 cycles (28 days each cycle) without further RT

    Reporting group title
    Unfavorable - Standard - PET negative
    Reporting group description
    ABVDx2 cycles (28 days each cycle)+ IN-RT 30Gy (+boost 6Gy to residual lesions).

    Reporting group title
    Unfavorable - Experimental - PET negative
    Reporting group description
    ABVDx 4 cycles (28 days each cycle), without RT

    Reporting group title
    Standard - PET positive
    Reporting group description
    Favorable : ABVDx1 cycles (28 days each cycle) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions) Unfavorable: ABVDx2 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions).

    Reporting group title
    Experimental - PET positive
    Reporting group description
    escalated BEACOPP x 2 cycles (21 days each cycle) + INRT30Gy (+boost 6Gy to residual lesions).

    Reporting group title
    Favorable - PET negative (after amendment 2010)
    Reporting group description
    ABVD x 1 cycle (28 days) + IN-RT 30GY (+boost 6GY to residual lesions).

    Reporting group title
    Unfavorable - PET negative (after amendment 2010)
    Reporting group description
    ABVD x 2 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions).

    Reporting group values
    Favorable - Standard - PET negative Favorable - Experimental - PET negative Unfavorable - Standard - PET negative Unfavorable - Experimental - PET negative Standard - PET positive Experimental - PET positive Favorable - PET negative (after amendment 2010) Unfavorable - PET negative (after amendment 2010) Total
    Number of subjects
    227 238 292 302 192 169 185 320 1925
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        median (full range (min-max))
    31 (15 to 49) 30 (15 to 49) 32 (15 to 70) 31 (16 to 70) 30 (15 to 66) 30 (15 to 70) 28 (16 to 49) 30 (16 to 68) -
    Gender categorical
    Units: Subjects
        Female
    96 124 151 165 94 74 101 181 986
        Male
    131 114 141 137 98 95 84 139 939
    Risk group
    Favorable/unfavorable, as collected in CRF.
    Units: Subjects
        Favorable
    224 235 12 12 57 47 185 12 784
        Unfavorable
    3 3 280 290 135 122 0 308 1141
    Ann Arbor stage
    Units: Subjects
        Stage I
    65 76 56 59 47 31 50 44 428
        Stage II
    161 162 232 243 144 136 134 276 1488
        Stage III
    1 0 2 0 1 2 1 0 7
        Stage IV
    0 0 2 0 0 0 0 0 2
    Baseline PET available (yes/no)
    Units: Subjects
        No
    8 11 14 15 14 9 5 8 84
        Yes
    219 227 278 287 178 160 180 312 1841
    PET after 2 cycles ABVD (local assessment)
    Units: Subjects
        Negative
    221 234 279 293 25 17 178 307 1554
        Positive
    6 3 13 9 167 152 6 13 369
        Missing
    0 1 0 0 0 0 1 0 2
    PET after 2 cycles ABVD (central review)
    Units: Subjects
        Negative
    164 181 222 227 13 6 122 243 1178
        Positive
    3 2 7 6 117 127 4 4 270
        Unknown/missing
    60 55 63 69 62 36 59 73 477
    Histology
    Units: Subjects
        Nodular Lymphocyte Predominant
    0 2 0 0 0 0 0 1 3
        Nodular Sclerosis
    175 175 252 249 148 135 149 285 1568
        Mixed Cellularity
    36 45 30 29 20 15 23 23 221
        Lymphocyte Depletion
    2 0 1 3 2 2 2 3 15
        Lymphocyte Rich Classical
    11 11 4 9 13 7 8 3 66
        Other
    3 5 5 12 9 10 3 5 52
    WHO performance status
    Units: Subjects
        WHO PS 0
    209 230 239 239 147 125 169 253 1611
        WHO PS 1
    18 7 51 60 44 41 14 63 298
        WHO PS 2
    0 1 2 3 1 3 2 3 15
        WHO PS 3
    0 0 0 0 0 0 0 1 1

    End points

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    End points reporting groups
    Reporting group title
    Favorable - Standard
    Reporting group description
    ABVD x 2 cycles (28 days each cycle)

    Reporting group title
    Favorable - Experimental
    Reporting group description
    ABVD x 2 cycles (28 days each cycle)

    Reporting group title
    Unfavorable - Standard
    Reporting group description
    ABVD x 2 cycles (28 days each cycle)

    Reporting group title
    Unfavorable - Experimental
    Reporting group description
    ABVD x 2 cycles (28 days each cycle)
    Reporting group title
    Favorable - Standard - PET negative
    Reporting group description
    ABVD x 1 cycle (28 days) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions)

    Reporting group title
    Favorable - Experimental - PET negative
    Reporting group description
    ABVD x 2 cycles (28 days each cycle) without further RT

    Reporting group title
    Unfavorable - Standard - PET negative
    Reporting group description
    ABVDx2 cycles (28 days each cycle)+ IN-RT 30Gy (+boost 6Gy to residual lesions).

    Reporting group title
    Unfavorable - Experimental - PET negative
    Reporting group description
    ABVDx 4 cycles (28 days each cycle), without RT

    Reporting group title
    Standard - PET positive
    Reporting group description
    Favorable : ABVDx1 cycles (28 days each cycle) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions) Unfavorable: ABVDx2 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions).

    Reporting group title
    Experimental - PET positive
    Reporting group description
    escalated BEACOPP x 2 cycles (21 days each cycle) + INRT30Gy (+boost 6Gy to residual lesions).

    Reporting group title
    Favorable - PET negative (after amendment 2010)
    Reporting group description
    ABVD x 1 cycle (28 days) + IN-RT 30GY (+boost 6GY to residual lesions).

    Reporting group title
    Unfavorable - PET negative (after amendment 2010)
    Reporting group description
    ABVD x 2 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions).

    Primary: PFS rate at 5 years (%) - Study population

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    End point title
    PFS rate at 5 years (%) - Study population [1]
    End point description
    Progression free survival (PFS) is counted from the date of randomization to the date of documentation of objective progression or death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up. Endpoint analyzed in the study population: all patients randomized in the trial, excluding patients who have not completed the 2 first ABVD cycles, or for whom no subsequent PET scan has been performed.
    End point type
    Primary
    End point timeframe
    Disease status evaluated after 2 cycles ABVD, at end of chemotherapy; at end of radiotherapy; at months 4, 6 and 9 during year 1 after end of treatment; every 3 months during year 2; every 6 months during years 3 and 4; yearly at years 5 to 10.
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.
    End point values
    Favorable - Standard - PET negative Favorable - Experimental - PET negative Unfavorable - Standard - PET negative Unfavorable - Experimental - PET negative Standard - PET positive Experimental - PET positive
    Number of subjects analysed
    227
    238
    292
    302
    192
    169
    Units: Percentage
        number (not applicable)
    99
    87.1
    92.1
    89.6
    77.4
    90.6
    Statistical analysis title
    Comparison Favorable PET negative: Exp vs. Std
    Comparison groups
    Favorable - Experimental - PET negative v Favorable - Standard - PET negative
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.986 [2]
    Method
    Regression, Cox
    Parameter type
    Hazard ratio (HR)
    Point estimate
    15.81
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.79
         upper limit
    66.07
    Notes
    [2] - p-value for non-inferiority test Non-inferiority margin: Hazard Ratio=3.2 Based on Cox model and Wald test - Asymptotically equivalent to Logrank test
    Statistical analysis title
    Comparison Unfavorable PET negative: Exp vs. Std
    Comparison groups
    Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative
    Number of subjects included in analysis
    594
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.908 [3]
    Method
    Regression, Cox
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    2.5
    Notes
    [3] - p-value for non-inferiority test Non-inferiority margin: Hazard Ratio=2.1 Based on Cox model and Wald test - Asymptotically equivalent to Logrank test
    Statistical analysis title
    Comparison PET positive: Exp vs. Std
    Comparison groups
    Standard - PET positive v Experimental - PET positive
    Number of subjects included in analysis
    361
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.23
         upper limit
    0.74

    Secondary: EFS rate at 5 years (%) - Study population

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    End point title
    EFS rate at 5 years (%) - Study population [4]
    End point description
    Event free survival (EFS) is counted from the date of randomization to the date of occurrence of death, objective progression, premature discontinuation of protocol therapy, or start of off protocol anti-cancer therapy. Patients without documented event at the time of the analysis are censored at the date of last follow-up. It was agreed by the DRC that off protocol anti-cancer therapy was to be restricted to therapy for HL; therapy for second malignancies was not considered as an event for EFS by the DRC. Endpoint analyzed in the study population: all patients randomized in the trial, excluding patients who have not completed the 2 first ABVD cycles, or for whom no subsequent PET scan has been performed.
    End point type
    Secondary
    End point timeframe
    Disease status evaluated after 2 cycles ABVD, at end of chemotherapy; at end of radiotherapy; at months 4, 6 and 9 during year 1 after end of treatment; every 3 months during year 2; every 6 months during years 3 and 4; yearly at years 5 to 10.
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.
    End point values
    Favorable - Standard - PET negative Favorable - Experimental - PET negative Unfavorable - Standard - PET negative Unfavorable - Experimental - PET negative Standard - PET positive Experimental - PET positive
    Number of subjects analysed
    227
    238
    292
    302
    192
    169
    Units: Percentage
        number (not applicable)
    96.3
    82.5
    87
    82.7
    71
    76.5
    Statistical analysis title
    Comparison Favorable PET negative: Exp vs. Std
    Comparison groups
    Favorable - Standard - PET negative v Favorable - Experimental - PET negative
    Number of subjects included in analysis
    465
    Analysis specification
    Pre-specified
    Analysis type
    other [5]
    Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    5.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.5
         upper limit
    11.36
    Notes
    [5] - No inferential test as non-inferiority margin for EFS not pre-specified.
    Statistical analysis title
    Comparison Unfavorable PET negative: Exp vs. Std
    Comparison groups
    Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative
    Number of subjects included in analysis
    594
    Analysis specification
    Pre-specified
    Analysis type
    other [6]
    Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.94
         upper limit
    2.17
    Notes
    [6] - No inferential test as non-inferiority margin for EFS not pre-specified.
    Statistical analysis title
    Comparison PET positive: Exp vs. Std
    Comparison groups
    Standard - PET positive v Experimental - PET positive
    Number of subjects included in analysis
    361
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.417
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.56
         upper limit
    1.27

    Secondary: OS rate at 5 years (%) - Study population

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    End point title
    OS rate at 5 years (%) - Study population [7]
    End point description
    Overall survival (OS) is counted from the date of randomization to the date of death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up. Endpoint analyzed in the study population: all patients randomized in the trial, excluding patients who have not completed the 2 first ABVD cycles, or for whom no subsequent PET scan has been performed.
    End point type
    Secondary
    End point timeframe
    Overall survival is counted from the date of randomization to the date of death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up.
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.
    End point values
    Favorable - Standard - PET negative Favorable - Experimental - PET negative Unfavorable - Standard - PET negative Unfavorable - Experimental - PET negative Standard - PET positive Experimental - PET positive
    Number of subjects analysed
    227
    238
    292
    302
    192
    169
    Units: Percentage
        number (not applicable)
    100
    99.6
    96.7
    99.3
    89.3
    96
    Statistical analysis title
    Comparison PET positive: Exp vs. Std
    Comparison groups
    Standard - PET positive v Experimental - PET positive
    Number of subjects included in analysis
    361
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.062
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.19
         upper limit
    1.07
    Statistical analysis title
    Comparison Unfavorable PET negative: Exp vs. Std
    Comparison groups
    Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative
    Number of subjects included in analysis
    594
    Analysis specification
    Pre-specified
    Analysis type
    other [8]
    Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.57
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.21
         upper limit
    1.58
    Notes
    [8] - No inferential test as non-inferiority margin for OS not pre-specified.

    Secondary: PFS rate at 5 years (%) - Per-protocol population

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    End point title
    PFS rate at 5 years (%) - Per-protocol population [9]
    End point description
    Progression free survival (PFS) is counted from the date of randomization to the date of documentation of objective progression or death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up. Endpoint analyzed in the per-protocol population: all "study" patients who were eligible for the trial, excluding patients who were later found to be in the wrong risk group (favorable/unfavorable; PET negative/positive).
    End point type
    Secondary
    End point timeframe
    Disease status evaluated after 2 cycles ABVD, at end of chemotherapy; at end of radiotherapy; at months 4, 6 and 9 during year 1 after end of treatment; every 3 months during year 2; every 6 months during years 3 and 4; yearly at years 5 to 10.
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.
    End point values
    Favorable - Standard - PET negative Favorable - Experimental - PET negative Unfavorable - Standard - PET negative Unfavorable - Experimental - PET negative Standard - PET positive Experimental - PET positive
    Number of subjects analysed
    221
    232
    268
    289
    172
    159
    Units: Percentage
        number (not applicable)
    98.9
    88.6
    91.7
    89.8
    75.9
    91.9
    Statistical analysis title
    Comparison Favorable PET negative: Exp vs. Std
    Comparison groups
    Favorable - Standard - PET negative v Favorable - Experimental - PET negative
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.976 [10]
    Method
    Regression, Cox
    Parameter type
    Hazard ratio (HR)
    Point estimate
    13.68
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.25
         upper limit
    57.55
    Notes
    [10] - p-value for non-inferiority test Non-inferiority margin: Hazard Ratio=3.2 Based on Cox model and Wald test - Asymptotically equivalent to Logrank test
    Statistical analysis title
    Comparison Unfavorable PET negative: Exp vs. Std
    Comparison groups
    Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative
    Number of subjects included in analysis
    557
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    P-value
    = 0.948 [11]
    Method
    Regression, Cox
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.75
         upper limit
    2.31
    Notes
    [11] - p-value for non-inferiority test Non-inferiority margin: Hazard Ratio=2.1 Based on Cox model and Wald test - Asymptotically equivalent to Logrank test
    Statistical analysis title
    Comparison PET positive: Exp vs. Std
    Comparison groups
    Standard - PET positive v Experimental - PET positive
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.18
         upper limit
    0.62

    Secondary: EFS rate at 5 years (%) - Per-protocol population

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    End point title
    EFS rate at 5 years (%) - Per-protocol population [12]
    End point description
    Event free survival (EFS) is counted from the date of randomization to the date of occurrence of death, objective progression, premature discontinuation of protocol therapy, or start of off protocol anti-cancer therapy. Patients without documented event at the time of the analysis are censored at the date of last follow-up. It was agreed by the DRC that off protocol anti-cancer therapy was to be restricted to therapy for HL; therapy for second malignancies was not considered as an event for EFS by the DRC. Endpoint analyzed in the per-protocol population: all "study" patients who were eligible for the trial, excluding patients who were later found to be in the wrong risk group (favorable/unfavorable; PET negative/positive).
    End point type
    Secondary
    End point timeframe
    Disease status evaluated after 2 cycles ABVD, at end of chemotherapy; at end of radiotherapy; at months 4, 6 and 9 during year 1 after end of treatment; every 3 months during year 2; every 6 months during years 3 and 4; yearly at years 5 to 10.
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.
    End point values
    Favorable - Standard - PET negative Favorable - Experimental - PET negative Unfavorable - Standard - PET negative Unfavorable - Experimental - PET negative Standard - PET positive Experimental - PET positive
    Number of subjects analysed
    221
    232
    268
    289
    172
    159
    Units: Percentage
        number (not applicable)
    96.7
    84.3
    87.6
    83.6
    71.7
    78.8
    Statistical analysis title
    Comparison Favorable PET negative: Exp vs. Std
    Comparison groups
    Favorable - Standard - PET negative v Favorable - Experimental - PET negative
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    other [13]
    Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    5.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.38
         upper limit
    11.98
    Notes
    [13] - No inferential test as non-inferiority margin for EFS not pre-specified.
    Statistical analysis title
    Comparison Unfavorable PET negative: Exp vs. Std
    Comparison groups
    Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative
    Number of subjects included in analysis
    557
    Analysis specification
    Pre-specified
    Analysis type
    other [14]
    Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.9
         upper limit
    2.2
    Notes
    [14] - No inferential test as non-inferiority margin for EFS not pre-specified.
    Statistical analysis title
    Comparison PET positive: Exp vs. Std
    Comparison groups
    Standard - PET positive v Experimental - PET positive
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.262
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.5
         upper limit
    1.21

    Secondary: OS rate at 5 years (%) - Per-protocol population

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    End point title
    OS rate at 5 years (%) - Per-protocol population [15]
    End point description
    Overall survival (OS) is counted from the date of randomization to the date of death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up. Endpoint analyzed in the per-protocol population: all "study" patients who were eligible for the trial, excluding patients who were later found to be in the wrong risk group (favorable/unfavorable; PET negative/positive).
    End point type
    Secondary
    End point timeframe
    Overall survival is counted from the date of randomization to the date of death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up.
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint at 5 years is not defined for arms where duration of follow-up is too short.
    End point values
    Favorable - Standard - PET negative Favorable - Experimental - PET negative Unfavorable - Standard - PET negative Unfavorable - Experimental - PET negative Standard - PET positive Experimental - PET positive
    Number of subjects analysed
    221
    232
    268
    289
    172
    159
    Units: Percentage
        number (not applicable)
    100
    99.6
    96.4
    98.2
    89.3
    95.7
    Statistical analysis title
    Comparison PET positive: Exp vs. Std
    Comparison groups
    Standard - PET positive v Experimental - PET positive
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.097
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.48
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.2
         upper limit
    1.16
    Statistical analysis title
    Comparison Unfavorable PET negative: Exp vs. Std
    Comparison groups
    Unfavorable - Standard - PET negative v Unfavorable - Experimental - PET negative
    Number of subjects included in analysis
    557
    Analysis specification
    Pre-specified
    Analysis type
    other [16]
    Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.16
         upper limit
    1.35
    Notes
    [16] - No inferential test as non-inferiority margin for OS not pre-specified.

    Secondary: PFS rate at 3 years (%) - Study population

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    End point title
    PFS rate at 3 years (%) - Study population [17]
    End point description
    Progression free survival (PFS) is counted from the date of randomization to the date of documentation of objective progression or death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up. Endpoint analyzed in the study population: all patients randomized in the trial, excluding patients who have not completed the 2 first ABVD cycles, or for whom no subsequent PET scan has been performed.
    End point type
    Secondary
    End point timeframe
    Disease status evaluated after 2 cycles ABVD, at end of chemotherapy; at end of radiotherapy; at months 4, 6 and 9 during year 1 after end of treatment; every 3 months during year 2; every 6 months during years 3 and 4; yearly at years 5 to 10.
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint (at 3 years) is not provided for the arms where the same endpoint at 5 years is provided.
    End point values
    Favorable - PET negative (after amendment 2010) Unfavorable - PET negative (after amendment 2010)
    Number of subjects analysed
    185
    320
    Units: Percentage
        number (not applicable)
    98.9
    95.5
    No statistical analyses for this end point

    Secondary: EFS rate at 3 years (%) - Study population

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    End point title
    EFS rate at 3 years (%) - Study population [18]
    End point description
    Event free survival (EFS) is counted from the date of randomization to the date of occurrence of death, objective progression, premature discontinuation of protocol therapy, or start of off protocol anti-cancer therapy. Patients without documented event at the time of the analysis are censored at the date of last follow-up. It was agreed by the DRC that off protocol anti-cancer therapy was to be restricted to therapy for HL; therapy for second malignancies was not considered as an event for EFS by the DRC. Endpoint analyzed in the study population: all patients randomized in the trial, excluding patients who have not completed the 2 first ABVD cycles, or for whom no subsequent PET scan has been performed.
    End point type
    Secondary
    End point timeframe
    Disease status evaluated after 2 cycles ABVD, at end of chemotherapy; at end of radiotherapy; at months 4, 6 and 9 during year 1 after end of treatment; every 3 months during year 2; every 6 months during years 3 and 4; yearly at years 5 to 10.
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint (at 3 years) is not provided for the arms where the same endpoint at 5 years is provided.
    End point values
    Favorable - PET negative (after amendment 2010) Unfavorable - PET negative (after amendment 2010)
    Number of subjects analysed
    185
    320
    Units: Percentage
        number (not applicable)
    96.7
    93.6
    No statistical analyses for this end point

    Secondary: OS rate at 3 years (%) - Study population

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    End point title
    OS rate at 3 years (%) - Study population [19]
    End point description
    Overall survival (OS) is counted from the date of randomization to the date of death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up. Endpoint analyzed in the study population: all patients randomized in the trial, excluding patients who have not completed the 2 first ABVD cycles, or for whom no subsequent PET scan has been performed.
    End point type
    Secondary
    End point timeframe
    Overall survival is counted from the date of randomization to the date of death (from any cause), whichever occurs first. Patients alive and free of progression are censored at the date of last follow-up.
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint (at 3 years) is not provided for the arms where the same endpoint at 5 years is provided.
    End point values
    Favorable - PET negative (after amendment 2010) Unfavorable - PET negative (after amendment 2010)
    Number of subjects analysed
    185
    320
    Units: Percentage
        number (not applicable)
    100
    99.7
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events and results of blood tests/ serum chemistry were collected on a CRF to be submitted at pre-specified time-points: before treatment start; after each cycle of CT; at end of CT; at end of RT; during follow-up.
    Adverse event reporting additional description
    CRF for AEs contains pre-specified items + additional boxes for all "other" AEs. (Few AEs are reported as "other" and are not reported as not available from the list of SOC). AEs are evaluated using CTC grading, SAEs using MedDra. Non-SAEs has not been collected specifically, therefore all AEs (grade 3 or more) will be reported in non-SAE section.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Favorable - Standard - PET negative
    Reporting group description
    ABVD x 3 cycles (28 days each cycle) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions). Safety population: Patients who started the allocated treatment.

    Reporting group title
    Favorable - Experimental - PET negative
    Reporting group description
    ABVD x 4 cycles (28 days each cycle) without further RT. Safety population: Patients who started the allocated treatment.

    Reporting group title
    Unfavorable - Standard - PET negative
    Reporting group description
    ABVD x 4 cycles (28 days each cycle)+ IN-RT 30Gy (+boost 6Gy to residual lesions). Safety population: Patients who started the allocated treatment.

    Reporting group title
    Unfavorable - Experimental - PET negative
    Reporting group description
    ABVD x 6 cycles (28 days each cycle), without RT. Safety population: Patients who started the allocated treatment.

    Reporting group title
    Standard - PET positive
    Reporting group description
    Favorable : ABVDx3 cycles (28 days each cycle) + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions) Unfavorable: ABVDx4 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions). Safety population: Patients who started the allocated treatment.

    Reporting group title
    Experimental - PET positive
    Reporting group description
    ABVD x 2 cycles (28 days each cycle) + escalated BEACOPP x 2 cycles (21 days each cycle) + INRT30Gy (+boost 6Gy to residual lesions). Safety population: Patients who started the allocated treatment.

    Reporting group title
    Favorable - PET negative (after amendment 2010)
    Reporting group description
    ABVD x 3 cycle (28 days) + IN-RT 30GY (+boost 6GY to residual lesions). Safety population: Patients who started the allocated treatment.

    Reporting group title
    Unfavorable - PET negative (after amendment 2010)
    Reporting group description
    ABVD x 4 cycles (28 days each cycle) + IN-RT 30Gy (+boost 6Gy to residual lesions). Safety population: Patients who started the allocated treatment.

    Reporting group title
    No PET after 2 cycles
    Reporting group description
    Started ABVD treatment but no PET after 2 cycles.

    Serious adverse events
    Favorable - Standard - PET negative Favorable - Experimental - PET negative Unfavorable - Standard - PET negative Unfavorable - Experimental - PET negative Standard - PET positive Experimental - PET positive Favorable - PET negative (after amendment 2010) Unfavorable - PET negative (after amendment 2010) No PET after 2 cycles
    Total subjects affected by serious adverse events
         subjects affected / exposed
    15 / 227 (6.61%)
    18 / 238 (7.56%)
    38 / 292 (13.01%)
    47 / 302 (15.56%)
    17 / 192 (8.85%)
    42 / 169 (24.85%)
    15 / 185 (8.11%)
    31 / 320 (9.69%)
    3 / 21 (14.29%)
         number of deaths (all causes)
    0
    3
    10
    6
    18
    7
    0
    1
    3
         number of deaths resulting from adverse events
    0
    0
    0
    1
    0
    1
    0
    0
    2
    Vascular disorders
    Deep vein thrombosis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    1 / 227 (0.44%)
    0 / 238 (0.00%)
    3 / 292 (1.03%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jugular vein thrombosis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Phlebitis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    2 / 302 (0.66%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    1 / 192 (0.52%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Contrast media allergy
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    1 / 227 (0.44%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Catheter site inflammation
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chills
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    2 / 320 (0.63%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related thrombosis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    1 / 302 (0.33%)
    1 / 192 (0.52%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperthermia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inflammation
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infusion site extravasation
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal inflammation
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    1 / 192 (0.52%)
    2 / 169 (1.18%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    3 / 227 (1.32%)
    1 / 238 (0.42%)
    2 / 292 (0.68%)
    6 / 302 (1.99%)
    0 / 192 (0.00%)
    9 / 169 (5.33%)
    1 / 185 (0.54%)
    6 / 320 (1.88%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
    1 / 2
    5 / 6
    0 / 0
    8 / 11
    0 / 1
    4 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sense of oppression
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    2 / 302 (0.66%)
    0 / 192 (0.00%)
    2 / 169 (1.18%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Insomnia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    2 / 302 (0.66%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatitis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pruritus genital
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Maternal exposure before pregnancy
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis chemical
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural complication
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    1 / 192 (0.52%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural fistula
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    1 / 192 (0.52%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiation dysphagia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    1 / 192 (0.52%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiation oesophagitis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    1 / 192 (0.52%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Coronary artery stenosis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracardiac thrombus
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    2 / 292 (0.68%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Left ventricular dysfunction
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-obstructive cardiomyopathy
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Palpitations
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    4 / 302 (1.32%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    4 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infiltration
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    1 / 192 (0.52%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal pain
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Painful respiration
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    1 / 227 (0.44%)
    0 / 238 (0.00%)
    4 / 292 (1.37%)
    4 / 302 (1.32%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    4 / 4
    4 / 4
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    2 / 292 (0.68%)
    2 / 302 (0.66%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    5 / 292 (1.71%)
    3 / 302 (0.99%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    1 / 320 (0.31%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 6
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Pulmonary toxicity
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    2 / 302 (0.66%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Blood and lymphatic system disorders
    Anaemia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    2 / 302 (0.66%)
    0 / 192 (0.00%)
    2 / 169 (1.18%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone marrow failure
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    3 / 169 (1.78%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    4 / 169 (2.37%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    4 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    3 / 227 (1.32%)
    3 / 238 (1.26%)
    2 / 292 (0.68%)
    6 / 302 (1.99%)
    0 / 192 (0.00%)
    17 / 169 (10.06%)
    6 / 185 (3.24%)
    5 / 320 (1.56%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 3
    2 / 2
    6 / 6
    0 / 0
    17 / 18
    8 / 8
    5 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    2 / 227 (0.88%)
    0 / 238 (0.00%)
    4 / 292 (1.37%)
    3 / 302 (0.99%)
    1 / 192 (0.52%)
    3 / 169 (1.78%)
    1 / 185 (0.54%)
    3 / 320 (0.94%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    4 / 4
    6 / 6
    1 / 1
    4 / 4
    1 / 1
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    4 / 169 (2.37%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    4 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    2 / 169 (1.18%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombotic microangiopathy
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral venous thrombosis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coma
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lhermitte's sign
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    1 / 192 (0.52%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental impairment
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tremor
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Oculogyric crisis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    1 / 185 (0.54%)
    2 / 320 (0.63%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    2 / 302 (0.66%)
    1 / 192 (0.52%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 2
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fissure
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal inflammation
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colonic pseudo-obstruction
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    2 / 227 (0.88%)
    3 / 238 (1.26%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    2 / 192 (1.04%)
    3 / 169 (1.78%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
    2 / 2
    0 / 0
    2 / 2
    2 / 3
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    2 / 227 (0.88%)
    3 / 238 (1.26%)
    1 / 292 (0.34%)
    2 / 302 (0.66%)
    0 / 192 (0.00%)
    3 / 169 (1.78%)
    0 / 185 (0.00%)
    2 / 320 (0.63%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
    1 / 1
    2 / 2
    0 / 0
    4 / 4
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctalgia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    1 / 227 (0.44%)
    3 / 238 (1.26%)
    2 / 292 (0.68%)
    1 / 302 (0.33%)
    1 / 192 (0.52%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    2 / 2
    1 / 1
    1 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis haemorrhagic
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Drug-induced liver injury
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic steatosis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic skin eruption
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    3 / 169 (1.78%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle contracture
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    1 / 185 (0.54%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperaldosteronism
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    1 / 320 (0.31%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    2 / 302 (0.66%)
    1 / 192 (0.52%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertriglyceridaemia
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    1 / 238 (0.42%)
    2 / 292 (0.68%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial sepsis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Bronchitis viral
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    1 / 192 (0.52%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopulmonary aspergillosis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Campylobacter gastroenteritis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    1 / 227 (0.44%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    1 / 292 (0.34%)
    0 / 302 (0.00%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    1 / 227 (0.44%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    1 / 169 (0.59%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    0 / 227 (0.00%)
    0 / 238 (0.00%)
    0 / 292 (0.00%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
    Additional description: From pharmacovigilance database.
         subjects affected / exposed
    1 / 227 (0.44%)
    0 / 238 (0.00%)
    2 / 292 (0.68%)
    1 / 302 (0.33%)
    0 / 192 (0.00%)
    0 / 169 (0.00%)
    0 / 185 (0.00%)
    0 / 320 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 /