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    Clinical Trial Results:
    A phase Ib, open-label study of oral BGJ398 in combination with oral BYL719 in adult patients with select advanced solid tumors

    Summary
    EudraCT number
    		 2013-001018-14
    Trial protocol
    		 DE   BE   NL  
    Global end of trial date
    23 Aug 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Sep 2017
    First version publication date
    02 Sep 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CBGJ398X2102
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01928459
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharmaceuticals AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Novartis Pharmaceuticals AG, Novartis Pharmaceuticals AG, +41 613241111,
    Scientific contact
    Novartis Pharmaceuticals AG, Novartis Pharmaceuticals AG, +41 613241111,
    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
    23 Aug 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Aug 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To study the safety and efficacy of the combination of BGJ398 with BYL719 in patients whose tumors express mutations to PIK3CA with or without alterations to FGFR 1-3.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulator requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Oct 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 4
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Singapore: 2
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    United States: 23
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Spain: 14
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Italy: 2
    Worldwide total number of subjects
    62
    EEA total number of subjects
    30
    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)
    43
    From 65 to 84 years
    19
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 At the time of the data cut-off date (23-Aug-2016), all patients had discontinued treatment. All 62 patients received at least one dose of BGJ398 or BYL719 and had at least one valid post-baseline safety assessment and were included in the FAS and Safety.

    Pre-assignment
    Screening details
    		 28 patients in the dose escalation part met the minimum exposure criterion and safety evaluation requirements and were included in the dose determining set (DDS). 58 were included in the pharmacokinetic analysis set (PAS), with only 4 patients, across three dose levels, excluded for not have having at least one blood sample providing evaluable PK.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 BGJ398 20mg + BYL719 300mg
    Arm description
    		 All patients, in both the dose escalation and dose expansion parts, were assigned to combination treatment with BGJ398 and BYL719. The starting dose of BGJ398 was 20 mg once daily on a 3 weeks on/1 week off schedule, which is 16% of the MTD identified in the first-in-human BGJ398 study [Study BGJ398X2101], as well as the lowest dose of BGJ398 that generated plasma concentrations that were consistently above the limit of quantitation. The starting dose of BYL719 for this study was 300 mg once daily, which is 75% of the MTD for BYL719 identified in the Phase 1 clinical study [Study BYL719X2101] but still associated with clinical activity. The starting dose of BYL719 was reduced to 300 mg once daily to address the potential of increased exposure to BYL719 when combined with BGJ398.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGJ398
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard, Gel
    Routes of administration
    Oral use
    Dosage and administration details
    BGJ398 hard gelatin capsules for oral use were supplied at dosage strengths of 5 mg, 25 mg, 100 mg, and 120 mg. Patients received BGJ398 once daily for the first 21 days of the 28-day cycle followed by a 7-day (1-week) break.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 film-coated tablets for oral use were supplied at dosage strengths of 10 mg, 50 mg, and 200 mg. Patients received BYL719 once daily continuously on a 28-day cycle.

    Arm title
    		 BGJ398 20mg + BYL719 400mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGJ398
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard, Gel
    Routes of administration
    Oral use
    Dosage and administration details
    BGJ398 hard gelatin capsules for oral use were supplied at dosage strengths of 5 mg, 25 mg, 100 mg, and 120 mg. Patients received BGJ398 once daily for the first 21 days of the 28-day cycle followed by a 7-day (1-week) break.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 film-coated tablets for oral use were supplied at dosage strengths of 10 mg, 50 mg, and 200 mg. Patients received BYL719 once daily continuously on a 28-day cycle.

    Arm title
    		 BGJ398 40mg + BYL719 300mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGJ398
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard, Gel
    Routes of administration
    Oral use
    Dosage and administration details
    BGJ398 hard gelatin capsules for oral use were supplied at dosage strengths of 5 mg, 25 mg, 100 mg, and 120 mg. Patients received BGJ398 once daily for the first 21 days of the 28-day cycle followed by a 7-day (1-week) break.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 film-coated tablets for oral use were supplied at dosage strengths of 10 mg, 50 mg, and 200 mg. Patients received BYL719 once daily continuously on a 28-day cycle.

    Arm title
    		 BGJ398 75mg + BYL719 300mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGJ398
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard, Gel
    Routes of administration
    Oral use
    Dosage and administration details
    BGJ398 hard gelatin capsules for oral use were supplied at dosage strengths of 5 mg, 25 mg, 100 mg, and 120 mg. Patients received BGJ398 once daily for the first 21 days of the 28-day cycle followed by a 7-day (1-week) break.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 film-coated tablets for oral use were supplied at dosage strengths of 10 mg, 50 mg, and 200 mg. Patients received BYL719 once daily continuously on a 28-day cycle.

    Arm title
    		 BGJ398 90mg + BYL719 300mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGJ398
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard, Gel
    Routes of administration
    Oral use
    Dosage and administration details
    BGJ398 hard gelatin capsules for oral use were supplied at dosage strengths of 5 mg, 25 mg, 100 mg, and 120 mg. Patients received BGJ398 once daily for the first 21 days of the 28-day cycle followed by a 7-day (1-week) break.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 film-coated tablets for oral use were supplied at dosage strengths of 10 mg, 50 mg, and 200 mg. Patients received BYL719 once daily continuously on a 28-day cycle.

    Arm title
    		 BGJ398 100mg + BYL719 300mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGJ398
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard, Gel
    Routes of administration
    Oral use
    Dosage and administration details
    BGJ398 hard gelatin capsules for oral use were supplied at dosage strengths of 5 mg, 25 mg, 100 mg, and 120 mg. Patients received BGJ398 once daily for the first 21 days of the 28-day cycle followed by a 7-day (1-week) break.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 film-coated tablets for oral use were supplied at dosage strengths of 10 mg, 50 mg, and 200 mg. Patients received BYL719 once daily continuously on a 28-day cycle.

    Arm title
    		 BGJ398 125mg + BYL719 300mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGJ398
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard, Gel
    Routes of administration
    Oral use
    Dosage and administration details
    BGJ398 hard gelatin capsules for oral use were supplied at dosage strengths of 5 mg, 25 mg, 100 mg, and 120 mg. Patients received BGJ398 once daily for the first 21 days of the 28-day cycle followed by a 7-day (1-week) break.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 film-coated tablets for oral use were supplied at dosage strengths of 10 mg, 50 mg, and 200 mg. Patients received BYL719 once daily continuously on a 28-day cycle.

    Number of subjects in period 1
    		BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Started
    4
    4
    6
    6
    5
    6
    31
    Completed
    0
    0
    0
    0
    0
    0
    0
    Not completed
    4
    4
    6
    6
    5
    6
    31
         Consent withdrawn by subject
    -
    -
    -
    1
    1
    -
    3
         Adverse event, non-fatal
    1
    -
    -
    1
    1
    1
    4
         Progressive disease
    3
    4
    6
    4
    3
    5
    23
         Protocol deviation
    -
    -
    -
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    BGJ398 20mg + BYL719 300mg
    Reporting group description
    		 All patients, in both the dose escalation and dose expansion parts, were assigned to combination treatment with BGJ398 and BYL719. The starting dose of BGJ398 was 20 mg once daily on a 3 weeks on/1 week off schedule, which is 16% of the MTD identified in the first-in-human BGJ398 study [Study BGJ398X2101], as well as the lowest dose of BGJ398 that generated plasma concentrations that were consistently above the limit of quantitation. The starting dose of BYL719 for this study was 300 mg once daily, which is 75% of the MTD for BYL719 identified in the Phase 1 clinical study [Study BYL719X2101] but still associated with clinical activity. The starting dose of BYL719 was reduced to 300 mg once daily to address the potential of increased exposure to BYL719 when combined with BGJ398.

    Reporting group title
    BGJ398 20mg + BYL719 400mg
    Reporting group description
    		 -

    Reporting group title
    BGJ398 40mg + BYL719 300mg
    Reporting group description
    		 -

    Reporting group title
    BGJ398 75mg + BYL719 300mg
    Reporting group description
    		 -

    Reporting group title
    BGJ398 90mg + BYL719 300mg
    Reporting group description
    		 -

    Reporting group title
    BGJ398 100mg + BYL719 300mg
    Reporting group description
    		 -

    Reporting group title
    BGJ398 125mg + BYL719 300mg
    Reporting group description
    		 -

    Reporting group values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg Total
    Number of subjects
    		 4 4 6 6 5 6 31 62
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 3 4 3 4 1 3 25 43
        From 65-84 years
    		 1 0 3 2 4 3 6 19
        85 years and over
    		 0 0 0 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56 ± 10.42 49.8 ± 11.59 62.8 ± 8.66 63 ± 7.13 65.4 ± 3.29 63.2 ± 11.58 56.1 ± 10.81 -
    Gender categorical
    Units: Subjects
        Female
    		 4 3 3 5 2 5 17 39
        Male
    		 0 1 3 1 3 1 14 23

    End points

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    End points reporting groups
    Reporting group title
    BGJ398 20mg + BYL719 300mg
    Reporting group description
    		 All patients, in both the dose escalation and dose expansion parts, were assigned to combination treatment with BGJ398 and BYL719. The starting dose of BGJ398 was 20 mg once daily on a 3 weeks on/1 week off schedule, which is 16% of the MTD identified in the first-in-human BGJ398 study [Study BGJ398X2101], as well as the lowest dose of BGJ398 that generated plasma concentrations that were consistently above the limit of quantitation. The starting dose of BYL719 for this study was 300 mg once daily, which is 75% of the MTD for BYL719 identified in the Phase 1 clinical study [Study BYL719X2101] but still associated with clinical activity. The starting dose of BYL719 was reduced to 300 mg once daily to address the potential of increased exposure to BYL719 when combined with BGJ398.

    Reporting group title
    BGJ398 20mg + BYL719 400mg
    Reporting group description
    		 -

    Reporting group title
    BGJ398 40mg + BYL719 300mg
    Reporting group description
    		 -

    Reporting group title
    BGJ398 75mg + BYL719 300mg
    Reporting group description
    		 -

    Reporting group title
    BGJ398 90mg + BYL719 300mg
    Reporting group description
    		 -

    Reporting group title
    BGJ398 100mg + BYL719 300mg
    Reporting group description
    		 -

    Reporting group title
    BGJ398 125mg + BYL719 300mg
    Reporting group description
    		 -

    Subject analysis set title
    Escalation BGJ398 125mg + BYL719 300mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All patients treated at Recommended Dose for Expansion (RDE).

    Subject analysis set title
    Expansion Treatment Arm 1
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Breast cancer patients with PIK3CA mutation and Fibroblast Growth Factor Receptor (FGFR) alteration (amplification, mutation or translocation).

    Subject analysis set title
    Expansion Treatment Arm 2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients, regardless of primary site of cancer, with PIK3CA mutation and no FGFR alteration. Two patients with breast cancer and no FGFR alteration were included in this arm.

    Subject analysis set title
    Expansion Treatment Arm 3
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Non-breast cancer patients with PIK3CA mutation and FGFR alteration.

    Primary: Posterior distribution of DLT rates at the time of the last dose-escalation meeting

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    End point title
    		 Posterior distribution of DLT rates at the time of the last dose-escalation meeting [1]
    End point description
    The primary variable in the study was the incidence rate of Dose-Limiting Toxicity (DLTs) in the 1st cycle of study treatment for patients with histologically/cytologically confirmed advanced or metastatic solid tumors carrying a PIK3CA mutation ± any FGFR genetic alterations, who have failed standard therapy and for whom no effective standard therapy exists in the Dose-Determining Set (DDS). Declaration of the Maximum-Tolerated Dose/Recommended dose for expansion (MTD/RDE) of the BGJ398 and BYL719 combination was guided by the probability of true DLT rate in Cycle 1 for patients in the DDS. This probability was estimated by the 5-parameter Bayesian logistic regression model (BLRM) guided by the escalation with overdose control (EWOC) principle. The DDS included all patients from the Safety set, and who were enrolled in the dose escalation part of the study, who either completed a minimum exposure requirement and had sufficient safety evaluations or experienced a DLT during Cycle 1
    End point type
    Primary
    End point timeframe
    first cycle (28-days; approximately 1 year)
    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: Bayesian analyses were used for this trial. The Bayesian modeling of the dose-toxicity relationship used for dose-escalation decision making and inference for the MTD was performed using internal Novartis R library functions (OncoBayes) created by Novartis’s Methodology group and was run using R version 3-2.3 in MODESIM/GPSII environment. We were not able to show these analyses here because they were in between doses and not groups as this is a single-arm treatment trial.
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    4
    4
    6
    6
    5
    6
    31
    Units: Posterior probabilities (%)
    number (not applicable)
        [0 - 0.16)
    0.905
    0.545
    0.888
    0.766
    0.683
    0.632
    0.542
        [0.16 - 0.35)
    0.095
    0.442
    0.111
    0.233
    0.313
    0.359
    0.404
        [0.35 - 1]
    0.001
    0.013
    0
    0.001
    0.004
    0.009
    0.054
    No statistical analyses for this end point

    Primary: Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 in dose escalation Phase

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    End point title
    		 Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 in dose escalation Phase [2]
    End point description
    Analyses for DLTs done in the DDS across all dose levels by primary system order class (SOC) and preferred terms.
    End point type
    Primary
    End point timeframe
    Cycle 1 (28-day cycle; approximately 1 year)
    Notes
    [2] - 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: Bayesian analyses were used for this trial. The Bayesian modeling of the dose-toxicity relationship used for dose-escalation decision making and inference for the MTD was performed using internal Novartis R library functions (OncoBayes) created by Novartis’s Methodology group and was run using R version 3-2.3 in MODESIM/GPSII environment. We were not able to show these analyses here because they were in between doses and not groups as this is a single-arm treatment trial.
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    3
    2
    5
    5
    3
    4
    6
    Units: Number of participants
        Any primary system organ class
    0
    0
    1
    1
    0
    1
    0
        GASTROINTESTINAL DISORDERS (SOC)
    0
    0
    0
    1
    0
    1
    0
        Stomatitis (Preferred term)
    0
    0
    0
    1
    0
    1
    0
        METABOLISM AND NUTRITION DISORDERS (SOC)
    0
    0
    1
    0
    0
    0
    0
        Hyperglycaemia (Preferred term)
    0
    0
    1
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Best Overall Response by Treatment as per RECIST 1.1

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    End point title
    		 Best Overall Response by Treatment as per RECIST 1.1
    End point description
    Clinical anti-tumor activity of BGJ398 and BYL719 combination was evaluated locally by the Investigator according to the Novartis guideline (Version 3.0) based on RECIST version 1.1 based on overall response rate (ORR: CR (Complete Response) + PR (Partial Response)) corresponding to disease control rate (DCR) i.e. best overall response of Stable Disease (SD). Analysis was done in the Full Analysis Set (FAS). FAS included all patients who received at least one dose of BGJ398 or BYL719. Patients were classified according to the planned treatment combination. The FAS was used for all listings of raw data. Unless otherwise specified, the FAS was the default analysis set used for all analyses.
    End point type
    Secondary
    End point timeframe
    Throughout the duration of the trial (approximately 3 years)
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    4
    4
    6
    6
    5
    6
    31
    Units: Number of Subjects
        Overall response rate (ORR) (CR or PR)
    0
    0
    0
    1
    1
    0
    4
        Disease control rate (DCR) (CR or PR or SD)
    2
    3
    3
    3
    4
    0
    19
    No statistical analyses for this end point

    Secondary: Best Overall Response by Treatment as per RECIST 1.1 - patients treated at MTD/RDE

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    End point title
    		 Best Overall Response by Treatment as per RECIST 1.1 - patients treated at MTD/RDE
    End point description
    Tumor response was evaluated locally by the Investigator according to the Novartis guideline (Version 3.0) based on RECIST version 1.1. Analysis was done in the FAS. MTD/RDE = Maximum tolerated dose/Recommended dose for expansion The BOR was summarized by treatment group for all patients and by treatment arms for patients treated at the MTD/RDE (1 cohort of patients in escalation part and 3 expansion arms).
    End point type
    Secondary
    End point timeframe
    Throughout the duration of the trial ((approximately 3 years)
    End point values
    		 Escalation BGJ398 125mg + BYL719 300mg Expansion Treatment Arm 1 Expansion Treatment Arm 2 Expansion Treatment Arm 3
    Number of subjects analysed
    7
    5
    12
    6
    Units: Number of subjects
        Overall response rate (ORR) (CR or PR)
    0
    0
    2
    2
        Disease control rate (DCR) (CR or PR or SD)
    4
    2
    8
    4
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS) per RECIST 1.1 for patients treated at MTD/RDE

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    End point title
    		 Progression-Free Survival (PFS) per RECIST 1.1 for patients treated at MTD/RDE
    End point description
    Analysis was done the FAS. PFS is defined as the time from the start date of study treatment to the date of the first documented disease progression or death due to any cause. PFS was provided for patients at MTD/RDE for each treatment arm.
    End point type
    Secondary
    End point timeframe
    Until disease progression or intolerable toxicity (approximately 3 years)
    End point values
    		 Escalation BGJ398 125mg + BYL719 300mg Expansion Treatment Arm 1 Expansion Treatment Arm 2 Expansion Treatment Arm 3
    Number of subjects analysed
    7
    5
    12
    6
    Units: Number of PFS Events
        Progression
    4
    2
    10
    4
        Death
    0
    1
    0
    0
        No. of censored
    3
    2
    2
    2
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve from Time Zero to 24 hour Post Dose for BGJ398 by Treatment

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    End point title
    		 Area Under the Concentration-Time Curve from Time Zero to 24 hour Post Dose for BGJ398 by Treatment
    End point description
    Pharmacokinetic paramter for BGJ398. AUC(0-24hr) = [mass x time x volume-1]. Analysis done in the pharmacokinetic analysis set (PAS). PAS consisted of all patients in FAS who had at least one blood sample providing evaluable pharmacokinetic data.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    4 [3]
    4 [4]
    4 [5]
    5 [6]
    3 [7]
    4 [8]
    29 [9]
    Units: hr*ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1
    23.4 ± 13.4
    48.8 ± 26.8
    248 ± 253
    217 ± 227
    432 ± 260
    786 ± 702
    836 ± 770
        Cycle 1 Day 15
    86 ± 83.7
    60.7 ± 53.2
    439 ± 687
    953 ± 1060
    2690 ± 1960
    1200 ± 960
    2890 ± 1870
        Cycle 2 Day 1
    58.5 ± 50.7
    48.9 ± 23.8
    550 ± 435
    328 ± 473
    1030 ± 551
    730 ± 815
    1050 ± 504
    Notes
    [3] - N = 4, 4, 3
    [4] - N = 4, 2, 3
    [5] - N = 4, 4, 3
    [6] - N = 5, 4, 4
    [7] - N = 3, 4, 3
    [8] - N = 4, 3, 2
    [9] - N = 29, 19, 17
    No statistical analyses for this end point

    Secondary: Maximum Observed Concentration after Drug Administration for BGJ398 by Treatment

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    End point title
    		 Maximum Observed Concentration after Drug Administration for BGJ398 by Treatment
    End point description
    Pharmacokinetic parameter for BCG398. Maximum observed concentration (Cmax ) after drug administration: [mass x volume-1]. Analysis done in PAS.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    4 [10]
    4 [11]
    6 [12]
    5 [13]
    4 [14]
    6 [15]
    28 [16]
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1
    5.75 ± 2.16
    10.5 ± 6.92
    40.1 ± 38.9
    40.6 ± 33
    71.3 ± 45.4
    59.2 ± 50.1
    128 ± 123
        Cycle 1 Day 15
    13.7 ± 11.1
    9.2 ± 6.39
    77.9 ± 90
    104 ± 88.1
    202 ± 136
    89.4 ± 63.2
    218 ± 126
        Cycle 2 Day 1
    12.7 ± 9.38
    9.06 ± 7.72
    43.8 ± 34.4
    37.5 ± 48.9
    93.5 ± 73.1
    111 ± 86
    116 ± 69.2
    Notes
    [10] - N = 4, 4, 3
    [11] - N = 4, 3, 4
    [12] - N = 6, 5, 4
    [13] - N = 5, 5, 4
    [14] - N = 4, 4, 4
    [15] - N = 6, 4, 3
    [16] - N = 28, 19, 22
    No statistical analyses for this end point

    Secondary: Pharmacokinetic Parameters for BGJ398 by Treatment

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    End point title
    		 Pharmacokinetic Parameters for BGJ398 by Treatment
    End point description
    Tmax=Time to reach Cmax [time]. T1/2 = Elimination half-life associated with the terminal slope (z) of a semi logarithmic concentration-time curve [time] Analysis done in the PAS.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    4 [17]
    4 [18]
    6 [19]
    5 [20]
    4 [21]
    6 [22]
    28 [23]
    Units: hour
    median (full range (min-max))
        Cycle 1 Day 1 (Tmax)
    2.5 (2 to 3.03)
    2.54 (1.92 to 4.08)
    2.05 (1.93 to 3)
    2.08 (2 to 3.08)
    2.57 (2 to 8)
    2.54 (2.02 to 7.97)
    2.93 (1 to 23.9)
        Cycle 1 Day 15 (Tmax)
    2.04 (1.97 to 3)
    4 (3 to 26.9)
    3 (2.03 to 4.25)
    3 (2 to 6)
    3.07 (1 to 3.83)
    3.42 (2 to 7)
    2.98 (1.77 to 4.33)
        Cycle 2 Day 1 (Tmax)
    2.08 (1.93 to 3)
    3.07 (2.08 to 4)
    2 (2 to 2.05)
    2.08 (2.08 to 4)
    2.5 (2 to 3.78)
    4.08 (4 to 6)
    4.02 (1.92 to 23.5)
        Cycle 1 Day 1 (T1/2)
    2.51 (1.9 to 3.1)
    3.08 (2.75 to 3.42)
    6.77 (5.9 to 7.65)
    3.22 (1.7 to 6.38)
    4.69 (2.55 to 5.22)
    7.95 (3.86 to 11.7)
    5.39 (3 to 9.59)
        Cycle 1 Day 15 (T1/2)
    3.1 (2.76 to 6.95)
    3.92 (3.92 to 3.92)
    5.24 (3.38 to 11.2)
    7.46 (6.4 to 33.6)
    20.5 (6.93 to 20.8)
    6.75 (5.66 to 9.45)
    12.8 (6.03 to 77.5)
        Cycle 2 Day 1 (T1/2)
    2.49 (2.32 to 3.1)
    3.43 (3.43 to 3.43)
    6.25 (5.24 to 8.59)
    4.93 (2.5 to 8.74)
    6.17 (4.65 to 10)
    7.73 (5.89 to 9.58)
    6.64 (2.16 to 10.4)
    Notes
    [17] - N = 4, 4, 4, 4, 3, 3
    [18] - N = 4, 2, 3, 1, 4, 1
    [19] - N= 6, 2, 5, 4, 4, 3
    [20] - N = 5, 5, 5, 4, 4, 3
    [21] - N = 4, 3, 4, 3, 4, 3
    [22] - N = 6, 4, 4, 3, 3, 2
    [23] - N = 28, 24, 19, 17, 22, 14
    No statistical analyses for this end point

    Secondary: Accumulation ratio (Racc) for BGJ398 by Treatment

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    End point title
    		 Accumulation ratio (Racc) for BGJ398 by Treatment
    End point description
    Racc = Accumulation ratio calculated as AUCtau,ss/AUCtau,dose1 where tau is the dosing interval where AUCtau, ss is defined as the area under the concentration-time curve following multiple dosing or at steady state. Analysis done in the PAS.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 15, Cycle 2 Day 1
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    4 [24]
    2 [25]
    2 [26]
    4 [27]
    3 [28]
    2 [29]
    17 [30]
    Units: accumulation ratio
    median (full range (min-max))
        Cycle 1 Day 15
    3.49 (1.68 to 4.98)
    2.02 (1.56 to 2.47)
    4.16 (2.74 to 5.68)
    5.5 (2.61 to 16.9)
    5.26 (4.97 to 12.2)
    3.18 (1.24 to 5.12)
    3.79 (0.394 to 343)
        Cycle 2 Day 1
    2.65 (0.483 to 4.2)
    1.21 (0.563 to 4.25)
    1.72 (0.768 to 2.67)
    1.02 (0.534 to 1.67)
    2.26 (1.77 to 4.16)
    10.1 (10.1 to 10.1)
    1.59 (0.744 to 34.8)
    Notes
    [24] - Cycle 2 Day 1 = 3
    [25] - Cycle 2 Day 1 = 3
    [26] - Cycle 2 Day 1 = 2
    [27] - Cycle 2 Day 1 = 4
    [28] - Cycle 2 Day 1 = 3
    [29] - Cycle 2 Day 1 = 1
    [30] - Cycle 2 Day 1 = 16
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve from Time Zero to 24 hour Post Dose for BYL719 by Treatment

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    End point title
    		 Area Under the Concentration-Time Curve from Time Zero to 24 hour Post Dose for BYL719 by Treatment
    End point description
    Pharmacokinetic parameter for BYL719. AUC(0-24hr) = [mass x time x volume-1]. Analysis done in the PAS.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    4 [31]
    4 [32]
    6 [33]
    5 [34]
    4 [35]
    3 [36]
    26 [37]
    Units: hr*ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1
    22400 ± 1820
    31600 ± 20800
    17900 ± 6810
    18200 ± 9820
    12700 ± 7450
    19300 ± 7580
    18500 ± 7810
        Cycle 1 Day 15
    34400 ± 10700
    16800 ± 3520
    21600 ± 7180
    19300 ± 5840
    23800 ± 8320
    25200 ± 12100
    25900 ± 9800
        Cycle 2 Day 1
    33300 ± 10500
    30800 ± 14100
    22300 ± 16000
    23700 ± 12000
    25000 ± 2070
    28600 ± 8440
    25200 ± 9370
    Notes
    [31] - Cycle 1 Day 1: N=4, Cycle 1 Day 15: N=4: Cycle 2 Day 1: N=3
    [32] - Cycle 1 Day 1: N=4, Cycle 1 Day 15: N=2: Cycle 2 Day 1: N=4
    [33] - Cycle 1 Day 1: N=6, Cycle 1 Day 15: N=3, Cycle 2 Day 1: N=5
    [34] - Cycle 1 Day 1: N=5,Cycle 1 Day 15: N=4, Cycle 2 Day 1: N=4
    [35] - Cycle 1 Day 1: N=3, Cycle 1 Day 15: N=4, Cycle 1 Day 15: N=4
    [36] - Cycle 1 Day 1: N=6, Cycle 1 Day 15: N=2, Cycle 2 Day 1: N=3
    [37] - Cycle 1 Day 1: N=26, Cycle 1 Day 15: N=18, Cycle 2 Day 1: N=20
    No statistical analyses for this end point

    Secondary: Maximum Observed Concentration after Drug Administration for BYL719 by Treatment

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    End point title
    		 Maximum Observed Concentration after Drug Administration for BYL719 by Treatment
    End point description
    Pharmacokinetic parameter for BYL719. Maximum observed concentration (Cmax ) after drug administration: [mass x volume-1]. Analysis done in PAS.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    4 [38]
    4 [39]
    6 [40]
    5 [41]
    4 [42]
    6 [43]
    28 [44]
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1
    2320 ± 914
    2770 ± 1480
    2100 ± 838
    1600 ± 806
    1440 ± 798
    1840 ± 1000
    1880 ± 948
        Cycle 1 Day 15
    2940 ± 1130
    1320 ± 551
    2350 ± 830
    1790 ± 686
    2100 ± 533
    1490 ± 666
    2130 ± 786
        Cycle 2 Day 1
    3600 ± 1830
    2240 ± 694
    1770 ± 898
    1730 ± 948
    2240 ± 614
    2340 ± 396
    2320 ± 841
    Notes
    [38] - Cycle 1 Day 1: N=4 Cycle 1 Day 15: N=4 Cycle 2 Day 1: N=3
    [39] - Cycle 1 Day 1: N=4 Cycle 1 Day 15: N=2 Cycle 2 Day 1: N=4
    [40] - Cycle 1 Day 1: N=6 Cycle 1 Day 15: N=4 Cycle 2 Day 1: N=5
    [41] - Cycle 1 Day 1: N=5 Cycle 1 Day 15: N=5 Cycle 2 Day 1: N=4
    [42] - Cycle 1 Day 1: N=4 Cycle 1 Day 15: N=4 Cycle 2 Day 1: N=4
    [43] - Cycle 1 Day 1: N=6 Cycle 1 Day 15: N=4 Cycle 2 Day 1: N=3
    [44] - Cycle 1 Day 1: N=28 Cycle 1 Day 15: N=14 Cycle 2 Day 1: N=22
    No statistical analyses for this end point

    Secondary: Pharmacokinetic Parameters for BYL719 by Treatment

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    End point title
    		 Pharmacokinetic Parameters for BYL719 by Treatment
    End point description
    Tmax=Time to reach Cmax [time]. T1/2 = Elimination half-life associated with the terminal slope (z) of a semi logarithmic concentration-time curve [time] Analysis done in the PAS.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    4 [45]
    4 [46]
    6 [47]
    5 [48]
    4 [49]
    6 [50]
    28 [51]
    Units: hour
    median (full range (min-max))
        Cycle 1 Day 1 (Tmax)
    3.08 (1.08 to 6)
    2.5 (1 to 6)
    2.08 (1 to 3.47)
    2 (1 to 2.08)
    1.61 (1 to 6)
    2.98 (1.08 to 3.08)
    2.08 (0.933 to 6.17)
        Cycle 1 Day 15 (Tmax)
    2.5 (1.97 to 3)
    3.79 (3 to 4.58)
    1.08 (1 to 4.25)
    4 (2 to 6)
    3.46 (1 to 24.5)
    3.87 (1.97 to 6)
    3 (0.967 to 6.28)
        Cycle 2 Day 1 (Tmax)
    3 (1.93 to 3.33)
    4.04 (2.08 to 4.13)
    2 (1.08 to 6)
    3.55 (2.08 to 4.15)
    2.38 (2 to 4)
    4 (3 to 4.08)
    2.99 (0.983 to 6.08)
        Cycle 1 Day 1 (T1/2)
    7.73 (7.58 to 9.32)
    5.72 (5.12 to 6.6)
    8.76 (6.6 to 17.4)
    7.46 (6.76 to 16.7)
    6.38 (6.29 to 6.51)
    7.05 (5.05 to 21.7)
    7.45 (4.56 to 14.4)
        Cycle 1 Day 15 (T1/2)
    7.82 (7.35 to 14.4)
    6.71 (6.71 to 6.71)
    9.86 (7.88 to 17.5)
    8.31 (8.21 to 10.5)
    6.96 (6.23 to 12.7)
    8.42 (5.69 to 11.2)
    8.24 (5.12 to 27)
        Cycle 2 Day 1 (T1/2)
    8.82 (6.37 to 12.6)
    7.36 (6.18 to 9.28)
    7.71 (6.17 to 13.8)
    8.9 (6.2 to 20.9)
    5.79 (4.94 to 18.7)
    7.6 (6.76 to 8.24)
    6.84 (4.52 to 11.1)
    Notes
    [45] - N = 4, 4, 3, 3, 4, 3
    [46] - N = 4, 2, 4, 3, 1, 3
    [47] - N = 6, 4, 5, 6, 3, 3
    [48] - N = 5, 5, 4, 5, 3, 4
    [49] - N = 4, 4, 4, 3, 3, 4
    [50] - N = 6, 4, 3, 6, 2, 3
    [51] - N = 28, 19, 22, 26, 18, 18
    No statistical analyses for this end point

    Secondary: Accumulation ratio (Racc) for BYL719 by Treatment

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    End point title
    		 Accumulation ratio (Racc) for BYL719 by Treatment
    End point description
    Racc = Accumulation ratio calculated as AUCtau,ss/AUCtau,dose1 where tau is the dosing interval where AUCtau, ss is defined as the area under the concentration-time curve following multiple dosing or at steady state. Analysis done in the PAS.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 15, Cycle 2 Day 1
    End point values
    		 BGJ398 20mg + BYL719 300mg BGJ398 20mg + BYL719 400mg BGJ398 40mg + BYL719 300mg BGJ398 75mg + BYL719 300mg BGJ398 90mg + BYL719 300mg BGJ398 100mg + BYL719 300mg BGJ398 125mg + BYL719 300mg
    Number of subjects analysed
    4 [52]
    4 [53]
    5 [54]
    5 [55]
    3 [56]
    3 [57]
    20 [58]
    Units: accumulation ratio
    median (full range (min-max))
        Cycle 1 Day 15
    1.66 (0.974 to 2.13)
    1.27 (0.989 to 1.55)
    1.5 (0.659 to 1.74)
    1.38 (0.842 to 3.39)
    2.01 (1.48 to 2.08)
    0.961 (0.854 to 1.07)
    1.33 (0.667 to 3.26)
        Cycle 2 Day 1
    1.41 (1.03 to 1.95)
    0.865 (0.662 to 5.12)
    1.25 (0.764 to 1.78)
    1.38 (1.24 to 2.22)
    2.15 (1.32 to 4.25)
    1.62 (1.23 to 2.76)
    1.44 (0.752 to 2.64)
    Notes
    [52] - Cycle 1 Day 15: N= 4 Cycle 2 Day 1: N=3
    [53] - Cycle 1 Day 15: N= 2 Cycle 2 Day 1: N=4
    [54] - Cycle 1 Day 15: N= 3 Cycle 2 Day 1: N=5
    [55] - Cycle 1 Day 15: N= 4 Cycle 2 Day 1: N=5
    [56] - Cycle 1 Day 15: N= 3 Cycle 2 Day 1: N=3
    [57] - Cycle 1 Day 15: N= 2 Cycle 2 Day 1: N=3
    [58] - Cycle 1 Day 15: N= 15 Cycle 2 Day 1: N=20
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious Adverse Events field "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    BGJ398 20mg@+ BYL719 300mg
    Reporting group description
    		 BGJ398 20mg@+ BYL719 300mg

    Reporting group title
    BGJ398 20mg@+ BYL719 400mg
    Reporting group description
    		 BGJ398 20mg@+ BYL719 400mg

    Reporting group title
    BGJ398 40mg@+ BYL719 300mg
    Reporting group description
    		 BGJ398 40mg@+ BYL719 300mg

    Reporting group title
    BGJ398 75mg@+ BYL719 300mg
    Reporting group description
    		 BGJ398 75mg@+ BYL719 300mg

    Reporting group title
    BGJ398 90mg@+ BYL719 300mg
    Reporting group description
    		 BGJ398 90mg@+ BYL719 300mg

    Reporting group title
    BGJ398 100mg@+ BYL719 300mg
    Reporting group description
    		 BGJ398 100mg@+ BYL719 300mg

    Reporting group title
    BGJ398 125mg@+ BYL719 300mg
    Reporting group description
    		 BGJ398 125mg@+ BYL719 300mg

    Reporting group title
    All@subjects
    Reporting group description
    		 All@subjects

    Serious adverse events
    		 BGJ398 20mg@+ BYL719 300mg BGJ398 20mg@+ BYL719 400mg BGJ398 40mg@+ BYL719 300mg BGJ398 75mg@+ BYL719 300mg BGJ398 90mg@+ BYL719 300mg BGJ398 100mg@+ BYL719 300mg BGJ398 125mg@+ BYL719 300mg All@subjects
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    2 / 4 (50.00%)
    3 / 6 (50.00%)
    4 / 6 (66.67%)
    0 / 5 (0.00%)
    3 / 6 (50.00%)
    11 / 31 (35.48%)
    27 / 62 (43.55%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    1
    2
    3
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    TUMOUR PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    Vascular disorders
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMATOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ILIAC VEIN OCCLUSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL SWELLING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    4 / 62 (6.45%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    HYPERSENSITIVITY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    DISORIENTATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Injury, poisoning and procedural complications
    FRACTURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    WOUND DECOMPOSITION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERONEAL NERVE PALSY
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN LOWER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CONSTIPATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPHAGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    NAUSEA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    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
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    STOMATITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    RASH MACULO-PAPULAR
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    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
    Renal and urinary disorders
    RENAL FAILURE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URETERIC OBSTRUCTION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MUSCULAR WEAKNESS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    Infections and infestations
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SKIN INFECTION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    HYPERGLYCAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 BGJ398 20mg@+ BYL719 300mg BGJ398 20mg@+ BYL719 400mg BGJ398 40mg@+ BYL719 300mg BGJ398 75mg@+ BYL719 300mg BGJ398 90mg@+ BYL719 300mg BGJ398 100mg@+ BYL719 300mg BGJ398 125mg@+ BYL719 300mg All@subjects
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    4 / 4 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    5 / 5 (100.00%)
    6 / 6 (100.00%)
    31 / 31 (100.00%)
    62 / 62 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    TUMOUR PAIN
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    Vascular disorders
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    HYPERTENSION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    2 / 62 (3.23%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    2
    HYPOTENSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    3 / 62 (4.84%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    3
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    7 / 31 (22.58%)
    11 / 62 (17.74%)
         occurrences all number
    1
    0
    2
    1
    0
    1
    10
    15
    FATIGUE
         subjects affected / exposed
    3 / 4 (75.00%)
    3 / 4 (75.00%)
    4 / 6 (66.67%)
    3 / 6 (50.00%)
    4 / 5 (80.00%)
    3 / 6 (50.00%)
    14 / 31 (45.16%)
    34 / 62 (54.84%)
         occurrences all number
    3
    3
    5
    4
    5
    3
    17
    40
    CHILLS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    3 / 31 (9.68%)
    5 / 62 (8.06%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    3
    5
    GAIT DISTURBANCE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    2
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    2
    INJECTION SITE HAEMATOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    MASS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    LOCALISED OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    2
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    3 / 5 (60.00%)
    1 / 6 (16.67%)
    10 / 31 (32.26%)
    15 / 62 (24.19%)
         occurrences all number
    0
    0
    1
    0
    4
    2
    16
    23
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    OEDEMA PERIPHERAL
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 6 (33.33%)
    3 / 31 (9.68%)
    7 / 62 (11.29%)
         occurrences all number
    1
    0
    0
    2
    0
    3
    3
    9
    PERIPHERAL SWELLING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    2
    PYREXIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    4 / 31 (12.90%)
    6 / 62 (9.68%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    6
    9
    SUPRAPUBIC PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    Immune system disorders
    HYPERSENSITIVITY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    3
    Respiratory, thoracic and mediastinal disorders
    DRY THROAT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    COUGH
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    2 / 6 (33.33%)
    3 / 31 (9.68%)
    10 / 62 (16.13%)
         occurrences all number
    0
    0
    5
    1
    1
    2
    3
    12
    DYSPHONIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    DYSPNOEA
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    5 / 31 (16.13%)
    9 / 62 (14.52%)
         occurrences all number
    2
    1
    0
    0
    1
    0
    5
    9
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    EPISTAXIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    4 / 31 (12.90%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    5
    5
    HAEMOPTYSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    HICCUPS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    2 / 31 (6.45%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    3
    5
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    1
    3
    PLEURITIC PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    WHEEZING
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    PRODUCTIVE COUGH
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    3 / 62 (4.84%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    3
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    3 / 62 (4.84%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    3
    DEPRESSION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    2 / 31 (6.45%)
    5 / 62 (8.06%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    2
    5
    INSOMNIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    1 / 6 (16.67%)
    3 / 31 (9.68%)
    8 / 62 (12.90%)
         occurrences all number
    1
    0
    0
    1
    2
    1
    3
    8
    IRRITABILITY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 6 (16.67%)
    10 / 31 (32.26%)
    12 / 62 (19.35%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    11
    13
    AMYLASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    2
    4
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 6 (16.67%)
    8 / 31 (25.81%)
    11 / 62 (17.74%)
         occurrences all number
    0
    1
    0
    0
    2
    1
    11
    15
    BLOOD 1,25-DIHYDROXYCHOLECALCIFEROL INCREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    2
    BLOOD 25-HYDROXYCHOLECALCIFEROL DECREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 6 (16.67%)
    3 / 31 (9.68%)
    6 / 62 (9.68%)
         occurrences all number
    0
    0
    3
    0
    2
    1
    3
    9
    BLOOD CREATINE PHOSPHOKINASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    3 / 62 (4.84%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    1
    3
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    4 / 6 (66.67%)
    10 / 31 (32.26%)
    18 / 62 (29.03%)
         occurrences all number
    0
    0
    1
    1
    3
    4
    24
    33
    BLOOD LACTATE DEHYDROGENASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    ELECTROCARDIOGRAM QT PROLONGED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    6 / 31 (19.35%)
    8 / 62 (12.90%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    8
    10
    LIPASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    4 / 31 (12.90%)
    7 / 62 (11.29%)
         occurrences all number
    0
    0
    2
    0
    2
    0
    7
    11
    LYMPHOCYTE COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    3
    PLATELET COUNT DECREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    2
    3
    TRANSAMINASES INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    2
    WEIGHT DECREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    2 / 6 (33.33%)
    5 / 31 (16.13%)
    12 / 62 (19.35%)
         occurrences all number
    1
    0
    0
    2
    2
    2
    5
    12
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    3 / 31 (9.68%)
    3 / 62 (4.84%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    4
    Injury, poisoning and procedural complications
    CONTUSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    Cardiac disorders
    TACHYCARDIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    Nervous system disorders
    AMNESIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    APHASIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    BALANCE DISORDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    DYSARTHRIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    2
    DIZZINESS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    4 / 62 (6.45%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    3
    6
    DYSGEUSIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    2 / 6 (33.33%)
    11 / 31 (35.48%)
    17 / 62 (27.42%)
         occurrences all number
    0
    0
    1
    1
    2
    2
    12
    18
    HEADACHE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    5 / 31 (16.13%)
    6 / 62 (9.68%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    6
    7
    HYPERAESTHESIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    HYPOAESTHESIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    LETHARGY
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    3 / 31 (9.68%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    3
    4
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    3 / 62 (4.84%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    2
    3
    PERONEAL NERVE PALSY
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    SYNCOPE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    2 / 6 (33.33%)
    5 / 31 (16.13%)
    11 / 62 (17.74%)
         occurrences all number
    0
    1
    3
    1
    1
    2
    13
    21
    LEUKOPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    2
    LYMPHOPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    3
    THROMBOCYTOPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    4 / 31 (12.90%)
    5 / 62 (8.06%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    6
    7
    Ear and labyrinth disorders
    EAR DISCOMFORT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    VERTIGO
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    Eye disorders
    CHORIORETINOPATHY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    2
    DIPLOPIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    DRY EYE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    7 / 31 (22.58%)
    8 / 62 (12.90%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    7
    8
    KERATITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    2 / 31 (6.45%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    4
    7
    OCULAR HYPERAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    2
    PERIORBITAL OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    RETINAL DETACHMENT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    2
    VISION BLURRED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    4 / 31 (12.90%)
    5 / 62 (8.06%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    5
    6
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    2
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    3 / 62 (4.84%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    0
    3
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    5 / 31 (16.13%)
    8 / 62 (12.90%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    5
    8
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    3 / 31 (9.68%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    4
    5
    ANAL FISSURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    ASCITES
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    2
    CHEILITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    2
    CONSTIPATION
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    3 / 6 (50.00%)
    8 / 31 (25.81%)
    15 / 62 (24.19%)
         occurrences all number
    1
    2
    0
    0
    1
    3
    11
    18
    DIARRHOEA
         subjects affected / exposed
    3 / 4 (75.00%)
    2 / 4 (50.00%)
    5 / 6 (83.33%)
    4 / 6 (66.67%)
    2 / 5 (40.00%)
    3 / 6 (50.00%)
    19 / 31 (61.29%)
    38 / 62 (61.29%)
         occurrences all number
    4
    4
    7
    5
    5
    3
    35
    63
    DRY MOUTH
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    3 / 6 (50.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    11 / 31 (35.48%)
    18 / 62 (29.03%)
         occurrences all number
    1
    2
    1
    3
    0
    1
    12
    20
    DYSPEPSIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    4 / 31 (12.90%)
    5 / 62 (8.06%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    7
    9
    DYSPHAGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    2
    GASTRITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 6 (33.33%)
    0 / 31 (0.00%)
    3 / 62 (4.84%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    3
    GINGIVAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    MELAENA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    2
    NAUSEA
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 4 (25.00%)
    4 / 6 (66.67%)
    4 / 6 (66.67%)
    1 / 5 (20.00%)
    3 / 6 (50.00%)
    15 / 31 (48.39%)
    31 / 62 (50.00%)
         occurrences all number
    4
    2
    4
    4
    1
    3
    22
    40
    PROCTALGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 6 (16.67%)
    1 / 31 (3.23%)
    4 / 62 (6.45%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    1
    4
    STOMATITIS
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    2 / 6 (33.33%)
    3 / 6 (50.00%)
    3 / 5 (60.00%)
    2 / 6 (33.33%)
    15 / 31 (48.39%)
    28 / 62 (45.16%)
         occurrences all number
    1
    3
    2
    4
    3
    2
    31
    46
    VOMITING
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    3 / 6 (50.00%)
    13 / 31 (41.94%)
    21 / 62 (33.87%)
         occurrences all number
    1
    4
    2
    1
    0
    3
    17
    28
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    0 / 6 (0.00%)
    8 / 31 (25.81%)
    12 / 62 (19.35%)
         occurrences all number
    0
    0
    1
    1
    2
    0
    8
    12
    BLISTER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    DRY SKIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    1 / 6 (16.67%)
    6 / 31 (19.35%)
    10 / 62 (16.13%)
         occurrences all number
    0
    0
    1
    1
    1
    1
    7
    11
    ERYTHEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    4 / 31 (12.90%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    5
    5
    NAIL BED INFLAMMATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    NAIL DISORDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    3 / 31 (9.68%)
    3 / 62 (4.84%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    4
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    6 / 31 (19.35%)
    7 / 62 (11.29%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    9
    10
    PRURITUS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    3 / 62 (4.84%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    2
    3
    RASH
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    1 / 6 (16.67%)
    5 / 31 (16.13%)
    10 / 62 (16.13%)
         occurrences all number
    0
    2
    0
    0
    2
    1
    5
    10
    RASH ERYTHEMATOUS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    2
    RASH MACULO-PAPULAR
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    4 / 31 (12.90%)
    8 / 62 (12.90%)
         occurrences all number
    1
    1
    2
    0
    1
    0
    4
    9
    RASH PRURITIC
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    2
    SKIN FISSURES
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    2
    4
    SKIN LESION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    SKIN NECROSIS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    XERODERMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    Renal and urinary disorders
    DYSURIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    2
    3
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    2
    MICTURITION DISORDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    4
    MICTURITION URGENCY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    2
    POLLAKIURIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    3 / 62 (4.84%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    4
    5
    URINARY RETENTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    URINARY TRACT OBSTRUCTION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    URINARY TRACT PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    2
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    1 / 6 (16.67%)
    2 / 31 (6.45%)
    6 / 62 (9.68%)
         occurrences all number
    0
    0
    0
    2
    1
    1
    2
    6
    BACK PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    1
    4
    FLANK PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    2
    MUSCLE SPASMS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    5 / 62 (8.06%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    2
    5
    MYALGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    2 / 31 (6.45%)
    3 / 62 (4.84%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    3
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    3
    6
    Infections and infestations
    ANAL INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    CELLULITIS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    CONJUNCTIVITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    3 / 31 (9.68%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    4
    5
    CYSTITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    2
    INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    INFLUENZA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    MUCOSAL INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    RASH PUSTULAR
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    SKIN INFECTION
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    5 / 62 (8.06%)
         occurrences all number
    2
    0
    0
    2
    0
    0
    1
    5
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    1 / 6 (16.67%)
    2 / 31 (6.45%)
    7 / 62 (11.29%)
         occurrences all number
    1
    0
    0
    2
    1
    1
    2
    7
    VAGINAL INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    VULVOVAGINAL MYCOTIC INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    3 / 5 (60.00%)
    3 / 6 (50.00%)
    16 / 31 (51.61%)
    28 / 62 (45.16%)
         occurrences all number
    2
    1
    2
    1
    3
    3
    21
    33
    DEHYDRATION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 6 (0.00%)
    2 / 31 (6.45%)
    5 / 62 (8.06%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    2
    5
    HYPERCALCAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    3 / 31 (9.68%)
    3 / 62 (4.84%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    4
    HYPERKALAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    2
    HYPERGLYCAEMIA
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    4 / 6 (66.67%)
    4 / 6 (66.67%)
    2 / 5 (40.00%)
    2 / 6 (33.33%)
    9 / 31 (29.03%)
    24 / 62 (38.71%)
         occurrences all number
    1
    4
    4
    6
    9
    5
    12
    41
    HYPERPHOSPHATAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    3 / 6 (50.00%)
    17 / 31 (54.84%)
    24 / 62 (38.71%)
         occurrences all number
    0
    0
    0
    3
    3
    4
    35
    45
    HYPOALBUMINAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 6 (16.67%)
    2 / 31 (6.45%)
    3 / 62 (4.84%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    3
    HYPOCALCAEMIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    1 / 31 (3.23%)
    2 / 62 (3.23%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    2
    HYPOCHLORAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    HYPOKALAEMIA
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    0 / 6 (0.00%)
    3 / 31 (9.68%)
    8 / 62 (12.90%)
         occurrences all number
    2
    0
    0
    1
    2
    0
    5
    10
    HYPOMAGNESAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    2 / 6 (33.33%)
    2 / 31 (6.45%)
    5 / 62 (8.06%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    2
    5
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 6 (16.67%)
    1 / 31 (3.23%)
    4 / 62 (6.45%)
         occurrences all number
    0
    2
    0
    0
    1
    1
    2
    6
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    0 / 6 (0.00%)
    4 / 31 (12.90%)
    7 / 62 (11.29%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    12
    15
    POLYDIPSIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 6 (0.00%)
    0 / 31 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    0
    0
    1
    0
    0
    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
    27 Jan 2015
    Guidelines for the management of pneumonitis were added as a result of implementation of an Urgent Safety Measure for BYL719. In addition, a letter was sent to all sites and Investigators participating in BYL719 studies on 19-Dec-2014 to implement Urgent Safety Measures immediately to adequately protect patients.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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