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    Clinical Trial Results:
    A Multicenter, Open-Label, Phase 2b Pilot Study to Evaluate the Efficacy and Safety of Quadruple Therapy (VX-222, Telaprevir, Peginterferon-Alfa-2 and Ribavirin) in Subjects With Genotype 1 Chronic Hepatitis C With Compensated Cirrhosis

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    2011-004150-26
    Trial protocol
    DE   GB   PL  
    Global end of trial date
    06 Feb 2014

    Results information
    Results version number
    v2(current)
    This version publication date
    13 Jul 2016
    First version publication date
    07 Aug 2015
    Other versions
    v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Address EudraCT system related issues identified through full data set Quality check review

    Trial information

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    Trial identification
    Sponsor protocol code
    VX11-222-106
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01516918
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Vertex Pharmaceuticals Incorporated
    Sponsor organisation address
    50 Northern Avenue, Boston, Massachusetts, United States, 02210-1862
    Public contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
    Scientific contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 Feb 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Feb 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the antiviral efficacy of a quadruple drug regimen (VX-222, telaprevir, pegylated interferon [Peg IFN], and ribavirin [RBV]) in subjects with Genotype 1 chronic hepatitis C (CHC), with compensated cirrhosis, who are treatment naïve or were non-responders (partial or null) or relapsers to previous Peg IFN/RBV therapy.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Conference on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    30 Jan 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Efficacy
    Long term follow-up duration
    1 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 22
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Canada: 4
    Country: Number of subjects enrolled
    United States: 57
    Worldwide total number of subjects
    92
    EEA total number of subjects
    31
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    85
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Subjects were enrolled at a total of 35 sites in the US (24 sites), Canada (1 site), Germany (6 sites), Poland (2 sites), and United Kingdom (2 sites).

    Pre-assignment
    Screening details
    A total of 92 subjects were enrolled in the quadruple regimen and received at least 1 dose of study drug.

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

    Arms
    Arm title
    Quadruple Regimen - All Subjects
    Arm description
    All subjects received active study drugs (quadruple regimen: VX-222, telaprevir,Peg-IFN, and RBV) for a fixed treatment duration of 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-222
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400 milligram (mg) twice daily in fed state.

    Investigational medicinal product name
    Telaprevir
    Investigational medicinal product code
    Other name
    Incivek, VX-950, Incivo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1125 mg twice daily in fed state.

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Copegus, RBV
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1000 mg per day for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg per day for subjects weighing greater than equal to (>=)75 kg, divided in 2 doses.

    Investigational medicinal product name
    Pegylated Interferon-Alfa-2a
    Investigational medicinal product code
    Other name
    Pegasys, Peg-IFN-alfa-2a
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    180 micrograms (mcg) once weekly.

    Number of subjects in period 1
    Quadruple Regimen - All Subjects
    Started
    92
    Completed
    77
    Not completed
    15
         Study Terminated by Sponsor
    8
         Death
    1
         Other Non-Compliance
    1
         Adverse Events
    3
         Lost to follow-up
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    -

    Reporting group values
    Overall Study Total
    Number of subjects
    92 92
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    55.6 ± 7.98 -
    Gender categorical
    Units: Subjects
        Female
    29 29
        Male
    63 63
    Subject analysis sets

    Subject analysis set title
    Treatment Naive
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects with Genotype 1 CHC, with compensated cirrhosis, who were treatment naïve.

    Subject analysis set title
    Prior Nonresponder
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects with Genotype 1 CHC, with compensated cirrhosis, who were prior nonresponders (that is, who received prior HCV treatment with Peg-IFN/RBV and experienced partial response [had >=2-log drop in HCV RNA at Week 12 of previous therapy but never achieved undetectable HCV RNA levels while on treatment] or who experienced null response (that is had <2-log decline in HCV RNA at Week 12 of therapy].

    Subject analysis set title
    Prior Relapser
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects with Genotype 1 CHC, with compensated cirrhosis, who were prior relapsers (that is, received prior HCV treatment with Peg-IFN/RBV, had undetectable HCV RNA at the end of treatment, but who subsequently had detectable HCV RNA).

    Subject analysis sets values
    Treatment Naive Prior Nonresponder Prior Relapser
    Number of subjects
    9
    76
    7
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    53.6 ± 5.98
    55.2 ± 8.11
    62.6 ± 5.41
    Gender categorical
    Units: Subjects
        Female
    4
    24
    1
        Male
    5
    52
    6

    End points

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    End points reporting groups
    Reporting group title
    Quadruple Regimen - All Subjects
    Reporting group description
    All subjects received active study drugs (quadruple regimen: VX-222, telaprevir,Peg-IFN, and RBV) for a fixed treatment duration of 24 weeks.

    Subject analysis set title
    Treatment Naive
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects with Genotype 1 CHC, with compensated cirrhosis, who were treatment naïve.

    Subject analysis set title
    Prior Nonresponder
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects with Genotype 1 CHC, with compensated cirrhosis, who were prior nonresponders (that is, who received prior HCV treatment with Peg-IFN/RBV and experienced partial response [had >=2-log drop in HCV RNA at Week 12 of previous therapy but never achieved undetectable HCV RNA levels while on treatment] or who experienced null response (that is had <2-log decline in HCV RNA at Week 12 of therapy].

    Subject analysis set title
    Prior Relapser
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects with Genotype 1 CHC, with compensated cirrhosis, who were prior relapsers (that is, received prior HCV treatment with Peg-IFN/RBV, had undetectable HCV RNA at the end of treatment, but who subsequently had detectable HCV RNA).

    Primary: Percentage of Subjects With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)

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    End point title
    Percentage of Subjects With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) [1]
    End point description
    SVR12 was defined as Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels below (<) the lower limit of quantification (LLOQ) at 12 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL). Full analysis set included all subjects who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    12 weeks after last planned dose of study drug (Week 36)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No inferential statistics were planned for this study.
    End point values
    Treatment Naive Prior Nonresponder Prior Relapser
    Number of subjects analysed
    9
    76
    7
    Units: percentage of subjects
        number (confidence interval 95%)
    66.7 (29.9 to 92.5)
    69.7 (58.1 to 79.8)
    100 (59 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    Percentage of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    AE: any untoward medical occurrence in a subject during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Safety set included all subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Up to Week 28
    End point values
    Quadruple Regimen - All Subjects
    Number of subjects analysed
    92
    Units: percentage of subjects
    number (not applicable)
        Subjects with any AEs
    98.9
        Subjects with SAEs
    15.2
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24)

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    End point title
    Percentage of Subjects With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR 24)
    End point description
    SVR24 was defined as HCV RNA Levels < LLOQ at 24 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The LLOQ was 25 IU/mL. Full analysis set included all subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    24 weeks after last planned dose of study drug (Week 48)
    End point values
    Treatment Naive Prior Nonresponder Prior Relapser
    Number of subjects analysed
    9
    76
    7
    Units: percentage of subjects
        number (confidence interval 95%)
    66.7 (29.9 to 92.5)
    67.1 (55.4 to 77.5)
    100 (59 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With HCV RNA Level <LLOQ at Planned End of Treatment (EOT)

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    End point title
    Percentage of Subjects With HCV RNA Level <LLOQ at Planned End of Treatment (EOT)
    End point description
    The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The LLOQ was 25 IU/mL. Full analysis set included all subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    EOT (Week 24)
    End point values
    Treatment Naive Prior Nonresponder Prior Relapser
    Number of subjects analysed
    9
    76
    7
    Units: percentage of subjects
        number (confidence interval 95%)
    100 (66.4 to 100)
    82.9 (72.5 to 90.6)
    100 (59 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Undetectable HCV RNA at Week, 2, 4, 8, 12, and 24

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    End point title
    Percentage of Subjects with Undetectable HCV RNA at Week, 2, 4, 8, 12, and 24
    End point description
    The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The limit of detection was 10 IU/mL. Full analysis set included all subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 2, 4, 8, 12 and 24
    End point values
    Treatment Naive Prior Nonresponder Prior Relapser
    Number of subjects analysed
    9
    76
    7
    Units: percentage of subjects
    number (not applicable)
        Week 2
    0
    21.1
    28.6
        Week 4
    77.8
    72.4
    85.7
        Week 8
    100
    85.5
    100
        Week 12
    100
    84.2
    100
        Week 24
    100
    72.4
    100
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With On Treatment Virologic Failure

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    End point title
    Percentage of Subjects With On Treatment Virologic Failure
    End point description
    On treatment virologic failure was defined as meeting any futility rule or completing assigned treatment duration and having detectable HCV RNA at EOT. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The LLOQ was 25 IU/mL. Futility rules: 1) HCV RNA levels >1000 IU/mL on Weeks 4 through 12; and 2) HCV RNA levels >LLOQ (repeated within 2 weeks to confirm detectability) after Week 12 through EOT (up to Week 24). Full analysis set included all subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    up to EOT (Week 24)
    End point values
    Treatment Naive Prior Nonresponder Prior Relapser
    Number of subjects analysed
    9
    76
    7
    Units: percentage of subjects
        number (not applicable)
    0
    7.9
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Relapse

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    End point title
    Percentage of Subjects With Relapse
    End point description
    Relapse was defined as having HCV RNA level <LLOQ at EOT followed by HCV RNA level >=LLOQ during follow-up. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The LLOQ was 25 IU/mL. Full analysis set included all subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    up to 24 weeks after last planned dose (up to Week 48)
    End point values
    Treatment Naive Prior Nonresponder Prior Relapser
    Number of subjects analysed
    9
    76
    7
    Units: percentage of subjects
        number (not applicable)
    33.3
    15.9
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with SVR12 by IL-28B Genotype

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    End point title
    Percentage of Subjects with SVR12 by IL-28B Genotype
    End point description
    SVR12 was defined as HCV RNA Levels <LLOQ at 12 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The LLOQ was 25 IU/mL. Data for this endpoint was not collected as the endpoint was omitted as per the ICH Harmonized Tripartite Guideline “Structure and Content of Clinical Study Reports: E3” and FDA Guidance Document “Submission of Abbreviated Reports and Synopses in Support of Marketing Applications.
    End point type
    Secondary
    End point timeframe
    12 weeks after last planned dose of study drug (Week 36)
    End point values
    Treatment Naive Prior Nonresponder Prior Relapser
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    Units: percentage of subjects
        number (not applicable)
    Notes
    [2] - The endpoint was omitted as specified in endpoint description.
    [3] - The endpoint was omitted as specified in endpoint description.
    [4] - The endpoint was omitted as specified in endpoint description.
    No statistical analyses for this end point

    Secondary: Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region

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    End point title
    Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region
    End point description
    Sequence analysis of the HCV NS3-4A region was to be performed to monitor telaprevir-resistant variants. HCV RNA was isolated from the plasma, amplified by reverse transcription-polymerase chain reaction (RT-PCR), and sequenced (sequencing assay limit of detection HCV RNA >=1000 IU/mL). Data for this endpoint was not collected as the endpoint was omitted as per the ICH Harmonized Tripartite Guideline “Structure and Content of Clinical Study Reports: E3” and FDA Guidance Document “Submission of Abbreviated Reports and Synopses in Support of Marketing Applications.
    End point type
    Secondary
    End point timeframe
    up to 24 weeks after last planned dose (up to Week 48)
    End point values
    Treatment Naive Prior Nonresponder Prior Relapser
    Number of subjects analysed
    0 [5]
    0 [6]
    0 [7]
    Units: subjects
    Notes
    [5] - The endpoint was omitted, as specified in endpoint description.
    [6] - The endpoint was omitted, as specified in endpoint description.
    [7] - The endpoint was omitted, as specified in endpoint description.
    No statistical analyses for this end point

    Secondary: VX-222, Telaprevir, and RBV Plasma Concentrations And Peg-IFN Serum Concentration

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    End point title
    VX-222, Telaprevir, and RBV Plasma Concentrations And Peg-IFN Serum Concentration
    End point description
    Data for this endpoint was not collected as the endpoint was omitted as per the ICH Harmonized Tripartite Guideline “Structure and Content of Clinical Study Reports: E3” and FDA Guidance Document “Submission of Abbreviated Reports and Synopses in Support of Marketing Applications.
    End point type
    Secondary
    End point timeframe
    A single blood sample at Day 1 (pre-dose), Week 2, and 8; 3 blood samples at Week 1, 4, and 12
    End point values
    Treatment Naive Prior Nonresponder Prior Relapser
    Number of subjects analysed
    0 [8]
    0 [9]
    0 [10]
    Units: nanogram per milliliter (ng/mL)
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    Notes
    [8] - The endpoint was omitted, as specified in endpoint description.
    [9] - The endpoint was omitted, as specified in endpoint description.
    [10] - The endpoint was omitted, as specified in endpoint description.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to Week 28
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Treatment Naive
    Reporting group description
    Subjects with Genotype 1 CHC, with compensated cirrhosis, who were treatment naïve.

    Reporting group title
    Prior Relapser
    Reporting group description
    Subjects with Genotype 1 CHC, with compensated cirrhosis, who were prior relapsers (that is, received prior HCV treatment with Peg-IFN/RBV, had undetectable HCV RNA at the end of treatment, but who subsequently had detectable HCV RNA).

    Reporting group title
    Prior Nonresponder
    Reporting group description
    Subjects with Genotype 1 CHC, with compensated cirrhosis, who were prior nonresponders (that is, who received prior HCV treatment with Peg-IFN/RBV and experienced partial response [had >=2-log drop in HCV RNA at Week 12 of previous therapy but never achieved undetectable HCV RNA levels while on treatment] or who experienced null response (that is had <2-log decline in HCV RNA at Week 12 of therapy].

    Serious adverse events
    Treatment Naive Prior Relapser Prior Nonresponder
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    13 / 76 (17.11%)
         number of deaths (all causes)
    0
    0
    1
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ilium fracture
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Lipase increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Vocal cord leukoplakia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Myositis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tendon disorder
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Treatment Naive Prior Relapser Prior Nonresponder
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 9 (100.00%)
    7 / 7 (100.00%)
    75 / 76 (98.68%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Hypertension
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Peripheral coldness
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Raynaud's phenomenon
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Venous thrombosis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    5 / 9 (55.56%)
    6 / 7 (85.71%)
    37 / 76 (48.68%)
         occurrences all number
    5
    6
    42
    Pyrexia
         subjects affected / exposed
    2 / 9 (22.22%)
    3 / 7 (42.86%)
    21 / 76 (27.63%)
         occurrences all number
    2
    4
    24
    Chills
         subjects affected / exposed
    1 / 9 (11.11%)
    3 / 7 (42.86%)
    12 / 76 (15.79%)
         occurrences all number
    1
    3
    13
    Influenza like illness
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    15 / 76 (19.74%)
         occurrences all number
    1
    0
    17
    Asthenia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    14 / 76 (18.42%)
         occurrences all number
    0
    1
    17
    Irritability
         subjects affected / exposed
    2 / 9 (22.22%)
    2 / 7 (28.57%)
    5 / 76 (6.58%)
         occurrences all number
    2
    2
    5
    Pain
         subjects affected / exposed
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    4 / 76 (5.26%)
         occurrences all number
    1
    2
    4
    Injection site erythema
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    4 / 76 (5.26%)
         occurrences all number
    1
    0
    4
    Malaise
         subjects affected / exposed
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    1 / 76 (1.32%)
         occurrences all number
    1
    2
    1
    Injection site reaction
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Chest pain
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    1 / 76 (1.32%)
         occurrences all number
    0
    1
    1
    Feeling abnormal
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Local swelling
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Oedema peripheral
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Temperature intolerance
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    1
    0
    1
    Early satiety
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    General physical health deterioration
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Injection site discolouration
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Injection site irritation
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Injection site pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Injection site pruritus
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Sluggishness
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    14 / 76 (18.42%)
         occurrences all number
    1
    2
    15
    Depression
         subjects affected / exposed
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    4 / 76 (5.26%)
         occurrences all number
    2
    2
    4
    Anxiety
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    4 / 76 (5.26%)
         occurrences all number
    1
    1
    4
    Depressed mood
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    5 / 76 (6.58%)
         occurrences all number
    0
    1
    5
    Sleep disorder
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Anger
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Mood altered
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Abnormal dreams
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Agitation
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    2
    Frustration
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Impatience
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Initial insomnia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Libido decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Loss of libido
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Mood swings
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Nervousness
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Genital rash
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Genital tract inflammation
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Injury, poisoning and procedural complications
    Laceration
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    0 / 76 (0.00%)
         occurrences all number
    1
    1
    0
    Contusion
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Excoriation
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Fall
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Lip injury
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Procedural site reaction
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Tooth fracture
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Investigations
    Blood glucose increased
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    3 / 76 (3.95%)
         occurrences all number
    1
    1
    4
    Weight decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    3 / 76 (3.95%)
         occurrences all number
    0
    1
    3
    Blood uric acid increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Haemoglobin decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    5
    Liver palpable subcostal
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Blood bilirubin increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Neutrophil count decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    1 / 76 (1.32%)
         occurrences all number
    0
    1
    1
    Weight increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Blood albumin decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Blood pressure systolic increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Blood urea increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Chest X-ray abnormal
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Heart rate decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    International normalised ratio increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Pancreatic enzymes increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Platelet count decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Protein total increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Transaminases increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Tachycardia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 9 (44.44%)
    3 / 7 (42.86%)
    26 / 76 (34.21%)
         occurrences all number
    5
    3
    29
    Neutropenia
         subjects affected / exposed
    3 / 9 (33.33%)
    0 / 7 (0.00%)
    14 / 76 (18.42%)
         occurrences all number
    5
    0
    21
    Thrombocytopenia
         subjects affected / exposed
    4 / 9 (44.44%)
    0 / 7 (0.00%)
    11 / 76 (14.47%)
         occurrences all number
    4
    0
    15
    Leukopenia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    1
    0
    3
    Lymphadenopathy
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 9 (33.33%)
    2 / 7 (28.57%)
    17 / 76 (22.37%)
         occurrences all number
    3
    2
    17
    Dyspnoea
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    12 / 76 (15.79%)
         occurrences all number
    0
    3
    13
    Dyspnoea exertional
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 7 (28.57%)
    12 / 76 (15.79%)
         occurrences all number
    0
    2
    12
    Epistaxis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    5 / 76 (6.58%)
         occurrences all number
    0
    0
    5
    Oropharyngeal pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    5 / 76 (6.58%)
         occurrences all number
    0
    0
    5
    Nasal congestion
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Nasal dryness
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    1 / 76 (1.32%)
         occurrences all number
    0
    1
    1
    Dry throat
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Haemoptysis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Increased upper airway secretion
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Nasal discomfort
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Pleuritic pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Productive cough
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 76 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory tract congestion
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Sinus congestion
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Tachypnoea
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    4 / 9 (44.44%)
    1 / 7 (14.29%)
    23 / 76 (30.26%)
         occurrences all number
    4
    1
    26
    Dizziness
         subjects affected / exposed
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    6 / 76 (7.89%)
         occurrences all number
    2
    4
    7
    Dysgeusia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    8 / 76 (10.53%)
         occurrences all number
    1
    0
    10
    Memory impairment
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    2 / 76 (2.63%)
         occurrences all number
    1
    1
    2
    Disturbance in attention
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Migraine
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Sinus headache
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    1
    0
    1
    Ageusia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Burning sensation
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Hyperaesthesia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Hypoaesthesia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 76 (0.00%)
         occurrences all number
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Resting tremor
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    2
    Restless legs syndrome
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Tremor
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 76 (0.00%)
         occurrences all number
    0
    1
    0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    4 / 76 (5.26%)
         occurrences all number
    1
    0
    5
    Dry eye
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    4
    Chalazion
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Eye inflammation
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Keratitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Lenticular opacities
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Uveitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Vitreous degeneration
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Tinnitus
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Vertigo
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    5 / 9 (55.56%)
    4 / 7 (57.14%)
    36 / 76 (47.37%)
         occurrences all number
    6
    6
    42
    Nausea
         subjects affected / exposed
    4 / 9 (44.44%)
    4 / 7 (57.14%)
    31 / 76 (40.79%)
         occurrences all number
    5
    5
    31
    Vomiting
         subjects affected / exposed
    1 / 9 (11.11%)
    3 / 7 (42.86%)
    19 / 76 (25.00%)
         occurrences all number
    1
    4
    23
    Anorectal discomfort
         subjects affected / exposed
    4 / 9 (44.44%)
    1 / 7 (14.29%)
    13 / 76 (17.11%)
         occurrences all number
    4
    1
    14
    Anal pruritus
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    16 / 76 (21.05%)
         occurrences all number
    1
    0
    18
    Abdominal pain upper
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    6 / 76 (7.89%)
         occurrences all number
    0
    0
    7
    Dry mouth
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    4 / 76 (5.26%)
         occurrences all number
    1
    0
    5
    Flatulence
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    4 / 76 (5.26%)
         occurrences all number
    0
    1
    4
    Frequent bowel movements
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    4 / 76 (5.26%)
         occurrences all number
    1
    0
    4
    Haemorrhoids
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    5 / 76 (6.58%)
         occurrences all number
    0
    0
    5
    Abdominal pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    4 / 76 (5.26%)
         occurrences all number
    0
    0
    4
    Constipation
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    2
    0
    3
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    4 / 76 (5.26%)
         occurrences all number
    0
    0
    4
    Proctalgia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    3 / 76 (3.95%)
         occurrences all number
    0
    1
    3
    Abdominal discomfort
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    1 / 76 (1.32%)
         occurrences all number
    1
    1
    1
    Cheilitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Dyspepsia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Toothache
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    1
    0
    2
    Gingival bleeding
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Rectal haemorrhage
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Abdominal distension
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    2
    Abdominal pain lower
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Abdominal rigidity
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Aphthous stomatitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Defaecation urgency
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Dysphagia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Faeces pale
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Gastric ulcer
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Gastrointestinal sounds abnormal
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Gingival inflammation
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Mouth ulceration
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Oral discomfort
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Oral mucosal erythema
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Oral pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Stomatitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Tongue coated
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    3
    0
    1
    Leukocyturia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Pollakiuria
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Urinary retention
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    4 / 76 (5.26%)
         occurrences all number
    0
    0
    5
    Jaundice
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Cholelithiasis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    3 / 9 (33.33%)
    3 / 7 (42.86%)
    25 / 76 (32.89%)
         occurrences all number
    5
    4
    32
    Pruritus
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    23 / 76 (30.26%)
         occurrences all number
    1
    2
    24
    Dry skin
         subjects affected / exposed
    3 / 9 (33.33%)
    0 / 7 (0.00%)
    12 / 76 (15.79%)
         occurrences all number
    3
    0
    12
    Alopecia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    9 / 76 (11.84%)
         occurrences all number
    0
    0
    10
    Pruritus generalised
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    1
    0
    4
    Skin lesion
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    2
    0
    3
    Eczema
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    5
    Rash pruritic
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    2 / 76 (2.63%)
         occurrences all number
    0
    2
    2
    Acne
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Dermatitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Petechiae
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Photosensitivity reaction
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    1
    0
    1
    Erythema
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    2
    Hyperhidrosis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 76 (0.00%)
         occurrences all number
    0
    1
    0
    Ingrowing nail
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Nail disorder
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Neurodermatitis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Papule
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Rash erythematous
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Skin exfoliation
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Skin fissures
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    2 / 9 (22.22%)
    1 / 7 (14.29%)
    14 / 76 (18.42%)
         occurrences all number
    2
    1
    15
    Arthralgia
         subjects affected / exposed
    1 / 9 (11.11%)
    2 / 7 (28.57%)
    13 / 76 (17.11%)
         occurrences all number
    2
    2
    14
    Pain in extremity
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    5 / 76 (6.58%)
         occurrences all number
    0
    0
    5
    Joint swelling
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Back pain
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    1 / 76 (1.32%)
         occurrences all number
    0
    1
    1
    Muscle spasms
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    1
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Neck pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Joint warmth
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    1
    0
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 9 (11.11%)
    3 / 7 (42.86%)
    15 / 76 (19.74%)
         occurrences all number
    1
    3
    15
    Hyperuricaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    5 / 76 (6.58%)
         occurrences all number
    0
    0
    6
    Hyperglycaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    4 / 76 (5.26%)
         occurrences all number
    0
    0
    4
    Hypokalaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    4 / 76 (5.26%)
         occurrences all number
    0
    0
    4
    Fluid retention
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Hypercalcaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Hyperlipidaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    4 / 76 (5.26%)
         occurrences all number
    1
    0
    4
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 7 (14.29%)
    3 / 76 (3.95%)
         occurrences all number
    2
    1
    3
    Bronchitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    3 / 76 (3.95%)
         occurrences all number
    0
    0
    3
    Urinary tract infection
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    1
    0
    3
    Otitis externa
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    2 / 76 (2.63%)
         occurrences all number
    0
    0
    2
    Abdominal abscess
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Anal abscess
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Candida infection
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 76 (0.00%)
         occurrences all number
    0
    1
    0
    Ear infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Eczema infected
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 7 (0.00%)
    0 / 76 (0.00%)
         occurrences all number
    1
    0
    0
    Fungal skin infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Gingival abscess
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Gingival infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Hordeolum
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Influenza
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Injection site infection
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 7 (14.29%)
    0 / 76 (0.00%)
         occurrences all number
    0
    1
    0
    Localised infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Pulpitis dental
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Sinusitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Subcutaneous abscess
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Tooth infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Vaginitis bacterial
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 7 (0.00%)
    1 / 76 (1.32%)
         occurrences all number
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Mar 2012
    Updated inclusion exclusion criteria.
    10 Apr 2012
    Updated inclusion exclusion criteria.
    05 Jun 2012
    This amendment involved modifying the study design, such that all subjects newly-enrolled under this version of the protocol received VX-222 combined with telaprevir, Peg-IFN, and RBV, for a total treatment duration of 24 weeks (all active drug). In addition, the response-guided treatment requirements were removed from the quadruple regimen, as current thought has shifted to making regimens as simple as possible for ease of compliance, and a quadruple regimen of 24 weeks is predicted to be as effective as a 48-week regimen. No further enrollment to be made into the VX-222-placebo, telaprevir, Peg-IFN, and RBV regimen, as this arm was no longer considered to be required for this Phase 2b pilot study, and its removal allowed all newly-enrolled subjects to receive a simplified, shortened duration regimen of active VX-222 combined with telaprevir, Peg-IFN and RBV for 24 weeks in this difficult-to-treat population. Title was modified to reflect the new study design for ongoing enrollment. Because the aforementioned changes result in this study now being an open-label study, safety monitoring by an independent data monitoring committee (DMC) is no longer necessary. Vertex personnel monitored for safety.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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