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    Clinical Trial Results:
    A phase Ib/II, open-label study of LJM716 in combination with BYL719 compared to taxane or irinotecan in patients with previously treated esophageal squamous cell carcinoma Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.

    Summary
    EudraCT number
    		 2012-005624-15
    Trial protocol
    		 ES   BE   GB   FR  
    Global end of trial date
    03 Jun 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Jul 2018
    First version publication date
    11 Jul 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CLJM716X2103
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01822613
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma 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
    03 Jun 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Jun 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To study the safety and efficacy of the combination of LJM716 and BYL719 against currently available treatments of physician’s choice in previously treated ESCC patients
    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 regulatory 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
    26 Jul 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
    Canada: 1
    Country: Number of subjects enrolled
    Hong Kong: 1
    Country: Number of subjects enrolled
    Korea, Republic of: 11
    Country: Number of subjects enrolled
    Singapore: 4
    Country: Number of subjects enrolled
    Taiwan: 19
    Country: Number of subjects enrolled
    United States: 3
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Belgium: 3
    Worldwide total number of subjects
    48
    EEA total number of subjects
    9
    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)
    30
    From 65 to 84 years
    18
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study design included a Phase 1b dose escalation portion to define the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) for the combination of LJM716 and alpelisib, followed by an open-label, randomized Phase 2 part to compare anti-tumor activity of LJM716-alpelisib combination versus physician's choice of second-line therapy.

    Pre-assignment
    Screening details
    		 The phase 2 part was not conducted as the study was terminated early due to limited anti-tumor activity with LJM716-alpelisib combination observed in phase 1b.

    Period 1
    Period 1 title
    Phase 1b (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
    		 LJM716 10/kg qw + BYL719 300 mg/day
    Arm description
    		 LJM716 10 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LJM716
    Investigational medicinal product code
    LJM716
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    LJM716 10 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    BYL719
    Other name
    Alpelisib
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Arm title
    		 LJM716 20 mg/kg qw + BYL719 300 mg/day
    Arm description
    		 LJM716 20 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LJM716
    Investigational medicinal product code
    LJM716
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    LJM716 20 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    BYL719
    Other name
    Alpelisib
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Arm title
    		 LJM716 30 mg/kg qw + BYL719 250 mg/day
    Arm description
    		 LJM716 30 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 250 mg was administered orally on a once daily schedule starting cycle 1 day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LJM716
    Investigational medicinal product code
    LJM716
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    LJM716 30 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    BYL719
    Other name
    Alpelisib
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 250 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Arm title
    		 LJM716 30 mg/kg + BYL719 300 mg/day
    Arm description
    		 LJM716 30 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LJM716
    Investigational medicinal product code
    LJM716
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    LJM716 30 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1.

    Investigational medicinal product name
    BYL719
    Investigational medicinal product code
    BYL719
    Other name
    Alpelisib
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Number of subjects in period 1
    		LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Started
    14
    15
    11
    8
    Dose determining analysis set
    10
    10
    9
    6
    Full analysis set
    14
    15
    11
    8
    Safety set
    14
    15
    11
    8
    Completed
    0
    0
    0
    0
    Not completed
    14
    15
    11
    8
         Physician decision
    2
    1
    -
    2
         Consent withdrawn by subject
    2
    1
    1
    -
         Adverse event, non-fatal
    1
    4
    2
    1
         Technical problems
    1
    -
    -
    -
         Death
    -
    2
    -
    -
         Progressive disease
    8
    7
    8
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    LJM716 10/kg qw + BYL719 300 mg/day
    Reporting group description
    		 LJM716 10 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Reporting group title
    LJM716 20 mg/kg qw + BYL719 300 mg/day
    Reporting group description
    		 LJM716 20 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Reporting group title
    LJM716 30 mg/kg qw + BYL719 250 mg/day
    Reporting group description
    		 LJM716 30 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 250 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Reporting group title
    LJM716 30 mg/kg + BYL719 300 mg/day
    Reporting group description
    		 LJM716 30 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Reporting group values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day Total
    Number of subjects
    		 14 15 11 8 48
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 8 12 6 4 30
        From 65-84 years
    		 6 3 5 4 18
        85 years and over
    		 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.6 ± 8.12 55.5 ± 11.41 61.5 ± 6.47 61.8 ± 6.88 -
    Gender categorical
    Units: Subjects
        Female
    		 4 0 2 2 8
        Male
    		 10 15 9 6 40

    End points

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    End points reporting groups
    Reporting group title
    LJM716 10/kg qw + BYL719 300 mg/day
    Reporting group description
    		 LJM716 10 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Reporting group title
    LJM716 20 mg/kg qw + BYL719 300 mg/day
    Reporting group description
    		 LJM716 20 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Reporting group title
    LJM716 30 mg/kg qw + BYL719 250 mg/day
    Reporting group description
    		 LJM716 30 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 250 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Reporting group title
    LJM716 30 mg/kg + BYL719 300 mg/day
    Reporting group description
    		 LJM716 30 mg/kg was given as a once weekly infusion beginning on cycle 1 day 1. BYL719 300 mg was administered orally on a once daily schedule starting cycle 1 day 1.

    Primary: Number of participants with dose limiting toxicities (DLTs)

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    End point title
    		 Number of participants with dose limiting toxicities (DLTs) [1]
    End point description
    The incidence of DLTs was assessed. The dose determining set (DDS) was analyzed. The DDS included all participants from the safety set who either completed a minimum exposure requirement and had sufficient safety evaluations or discontinued prematurely due to a DLT during the DLT assessment period. The DLT assessment period was defined as the 28-day period beginning with the first dose of study drug. The safety set included all participants who received at least one dose of alpelisib or LJM716, and had at least one valid post-baseline safety assessment.
    End point type
    Primary
    End point timeframe
    8 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive summary statistics only apply to this end point.
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    10
    10
    9
    6
    Units: Participants
        Participants with at least one event
    3
    3
    2
    2
        Decreased appetite
    0
    1
    0
    0
        Fatigue
    1
    0
    0
    0
        Hyperbilirubinaemia
    0
    1
    0
    0
        Hyperglycaemia
    2
    1
    2
    1
        Vomiting
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of participants with best overall response (BOR)

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    End point title
    		 Number of participants with best overall response (BOR)
    End point description
    The number of participants with complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) or unknown status was assessed. BOR was based on Investigator's assessment of disease status using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
    End point type
    Secondary
    End point timeframe
    about 4 months
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    14
    15
    11
    8
    Units: Participants
        CR
    0
    0
    0
    0
        PR
    0
    4
    1
    1
        SD
    4
    2
    3
    1
        PD
    6
    7
    6
    4
        Unknown
    4
    2
    1
    2
    No statistical analyses for this end point

    Secondary: Overall response rate (ORR)

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    End point title
    		 Overall response rate (ORR)
    End point description
    End point type
    Secondary
    End point timeframe
    The number of participants with CR or PR was assessed.
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    14
    15
    11
    8
    Units: Participants
    0
    4
    1
    1
    No statistical analyses for this end point

    Secondary: Disease control rate (DCR)

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    End point title
    		 Disease control rate (DCR)
    End point description
    End point type
    Secondary
    End point timeframe
    The number of participants with CR, PR or SD was assessed.
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    14
    15
    11
    8
    Units: Participants
    4
    6
    4
    2
    No statistical analyses for this end point

    Secondary: Progression free survival (PFS)

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    End point title
    		 Progression free survival (PFS)
    End point description
    PFS was defined as the time from the date of randomization to the date of first radiologically documented progression or death due to any cause.
    End point type
    Secondary
    End point timeframe
    about 5 months
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    14
    15
    11
    8
    Units: months
        median (confidence interval 95%)
    2.3 (1.31 to 4.96)
    1.86 (1.08 to 4.14)
    2.56 (1.22 to 4.07)
    1.94 (1.18 to 3.06)
    No statistical analyses for this end point

    Secondary: PK parameter for LJM716: AUClast

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    End point title
    		 PK parameter for LJM716: AUClast
    End point description
    AUClast = the area under the concentration-time curve from time zero to the last measurable concentration time sampling. Participants with non-missing values were analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1, day and cycle 3, day 1
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    14
    15
    11
    8
    Units: hr*ng/mL
    arithmetic mean (standard deviation)
        Cycle 1, day 1 (n=10,11,9,6)
    18569 ± 5373
    32679 ± 7010
    56503 ± 8979
    51053 ± 5663
        Cycle 3, day 1 (n=4,4,3,1)
    49069 ± 12677
    71939 ± 29197
    131967 ± 20983
    172205 ± 9999
    No statistical analyses for this end point

    Secondary: PK parameter for LJM716: Cmax

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    End point title
    		 PK parameter for LJM716: Cmax
    End point description
    Cmax = maximum observed concentration after drug administration. Participants with non-missing values were analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1, day 1 and cycle 3, day 1
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    14
    15
    11
    8
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1, day 1 (n=13,13,10,8)
    196 ± 43
    364 ± 91.2
    597 ± 87
    561 ± 85.2
        Cycle 3, day 1 (n=7,5,5,3)
    356 ± 125
    660 ± 203
    1106 ± 189
    1143 ± 150
    No statistical analyses for this end point

    Secondary: PK parameter for for BYL719 (alpelisib): AUClast

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    End point title
    		 PK parameter for for BYL719 (alpelisib): AUClast
    End point description
    AUClast = the area under the concentration-time curve from time zero to the last measurable concentration sampling time. Participants with non-missing values were analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1, day 1 and cycle 3, day 1
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    14
    15
    11
    8
    Units: hr*ng/mL
    arithmetic mean (standard deviation)
        Cycle 1, day 1 (n=12,11,9,5)
    21860 ± 12022
    23121 ± 10830
    19944 ± 9389
    26814 ± 4462
        Cycle 3, day 1 (n=4,4,3,1)
    21344 ± 13343
    21819 ± 8394
    23164 ± 6419
    24275 ± 9999
    No statistical analyses for this end point

    Secondary: PK parameter for BYL719 (alpelisib): Cmax

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    End point title
    		 PK parameter for BYL719 (alpelisib): Cmax
    End point description
    Cmax = maximum observed concentration after drug administration. Participants with non-missing values were analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1, day 1 and cycle 3, day 1
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    14
    15
    11
    8
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1, day 1 (n=14,13,11,6)
    1873 ± 1119
    2147 ± 1046
    1478 ± 645
    2208 ± 493
        Cycle 3, day 1 (n=5,5,5,3)
    1579 ± 1051
    1444 ± 1001
    1582 ± 610
    1873 ± 1081
    No statistical analyses for this end point

    Secondary: PK parameter for BYL719 (alpelisib): Tmax

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    End point title
    		 PK parameter for BYL719 (alpelisib): Tmax
    End point description
    Tmax = the time to reach the maximum concentration after drug administration. Participants with non-missing values were analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1, day 1 and cycle 3, day 1
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    14
    15
    11
    8
    Units: hour
    median (full range (min-max))
        Cycle 1, day 1 (n=14,4,4,4)
    4 (1.97 to 7.95)
    4 (1.9 to 8.68)
    4 (2 to 7)
    4 (1.92 to 7.98)
        Cycle 3, day 1 (n=5,5,5,3)
    4 (1.98 to 23.9)
    4.17 (1.85 to 23.8)
    2 (0.5 to 7.4)
    4.15 (2 to 7.93)
    No statistical analyses for this end point

    Secondary: PK parameter for BYL719 (alpelisib): AUCinf

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    End point title
    		 PK parameter for BYL719 (alpelisib): AUCinf
    End point description
    AUCinf = the area under the concentration-time curve from time zero to infinity. Participants with non-missing values were analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1, day 1 and cycle 3, day 1
    End point values
    		 LJM716 10/kg qw + BYL719 300 mg/day LJM716 20 mg/kg qw + BYL719 300 mg/day LJM716 30 mg/kg qw + BYL719 250 mg/day LJM716 30 mg/kg + BYL719 300 mg/day
    Number of subjects analysed
    14
    15
    11
    8
    Units: hr*ng/mL
    arithmetic mean (standard deviation)
        Cycle 1, day 1 (n=6,5,5,3)
    31082 ± 8890
    28498 ± 12438
    19192 ± 7395
    28165 ± 3122
        Cycle 3, day 1(n=2,1,2,1)
    13515 ± 10898
    32305 ± 9999
    23910 ± 8299
    24961 ± 9999
    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
    LJM716 10 mg/kg QW@+ BYL719 300 mg/day
    Reporting group description
    		 LJM716 10 mg/kg QW@+ BYL719 300 mg/day

    Reporting group title
    LJM716 20 mg/kg QW@+ BYL719 300 mg/day
    Reporting group description
    		 LJM716 20 mg/kg QW@+ BYL719 300 mg/day

    Reporting group title
    LJM716 30 mg/kg QW@+ BYL719 250 mg/day
    Reporting group description
    		 LJM716 30 mg/kg QW@+ BYL719 250 mg/day

    Reporting group title
    LJM716 30 mg/kg QW@+ BYL719 300 mg/day
    Reporting group description
    		 LJM716 30 mg/kg QW@+ BYL719 300 mg/day

    Reporting group title
    All@patients
    Reporting group description
    		 All@patients

    Serious adverse events
    		 LJM716 10 mg/kg QW@+ BYL719 300 mg/day LJM716 20 mg/kg QW@+ BYL719 300 mg/day LJM716 30 mg/kg QW@+ BYL719 250 mg/day LJM716 30 mg/kg QW@+ BYL719 300 mg/day All@patients
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 14 (92.86%)
    9 / 15 (60.00%)
    4 / 11 (36.36%)
    6 / 8 (75.00%)
    32 / 48 (66.67%)
         number of deaths (all causes)
    5
    3
    1
    0
    9
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    TUMOUR NECROSIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY DISTRESS SYNDROME
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    DYSPNOEA
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    HAEMOPTYSIS
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTERSTITIAL LUNG DISEASE
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    OESOPHAGOBRONCHIAL FISTULA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PLEURAL FISTULA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMOMEDIASTINUM
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    3 / 48 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Psychiatric disorders
    COMPLETED SUICIDE
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    WEIGHT DECREASED
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    Congenital, familial and genetic disorders
    TRACHEO-OESOPHAGEAL FISTULA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    Cardiac disorders
    ARRHYTHMIA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERICARDIAL EFFUSION
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    SUPRAVENTRICULAR TACHYCARDIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    BRAIN INJURY
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    COMA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Gastrointestinal disorders
    AORTO-OESOPHAGEAL FISTULA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPHAGIA
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    4 / 48 (8.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTRIC ULCER
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    OESOPHAGEAL ACHALASIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    OESOPHAGEAL FISTULA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    OESOPHAGEAL PERFORATION
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    STOMATITIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    1 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    SUBCUTANEOUS EMPHYSEMA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    URINARY TRACT OBSTRUCTION
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    ARTHRITIS BACTERIAL
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    BACTERAEMIA
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CYSTITIS
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    LUNG INFECTION
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    PNEUMONIA
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    RESPIRATORY SYNCYTIAL VIRUS INFECTION
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    SEPSIS
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    DEHYDRATION
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERCALCAEMIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    HYPERGLYCAEMIA
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    3 / 48 (6.25%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOPHAGIA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 LJM716 10 mg/kg QW@+ BYL719 300 mg/day LJM716 20 mg/kg QW@+ BYL719 300 mg/day LJM716 30 mg/kg QW@+ BYL719 250 mg/day LJM716 30 mg/kg QW@+ BYL719 300 mg/day All@patients
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 14 (100.00%)
    15 / 15 (100.00%)
    11 / 11 (100.00%)
    8 / 8 (100.00%)
    48 / 48 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    CANCER PAIN
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    TUMOUR PAIN
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    Vascular disorders
    HAEMATOMA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    HYPERTENSION
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    1
    2
    0
    3
    HYPOTENSION
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    2
    1
    0
    0
    3
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    2 / 14 (14.29%)
    3 / 15 (20.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    5 / 48 (10.42%)
         occurrences all number
    2
    3
    0
    0
    5
    CHEST DISCOMFORT
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    CHILLS
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    2
    1
    1
    0
    4
    FATIGUE
         subjects affected / exposed
    6 / 14 (42.86%)
    5 / 15 (33.33%)
    6 / 11 (54.55%)
    4 / 8 (50.00%)
    21 / 48 (43.75%)
         occurrences all number
    8
    15
    7
    4
    34
    GENERALISED OEDEMA
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    MALAISE
         subjects affected / exposed
    3 / 14 (21.43%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    4 / 48 (8.33%)
         occurrences all number
    3
    1
    0
    0
    4
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    2 / 14 (14.29%)
    4 / 15 (26.67%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    7 / 48 (14.58%)
         occurrences all number
    2
    4
    0
    2
    8
    OEDEMA PERIPHERAL
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    4 / 48 (8.33%)
         occurrences all number
    3
    1
    1
    1
    6
    PAIN
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    0
    0
    2
    2
    PERIPHERAL SWELLING
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    PYREXIA
         subjects affected / exposed
    5 / 14 (35.71%)
    5 / 15 (33.33%)
    1 / 11 (9.09%)
    2 / 8 (25.00%)
    13 / 48 (27.08%)
         occurrences all number
    10
    6
    1
    2
    19
    Immune system disorders
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    2
    0
    0
    0
    2
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    5 / 14 (35.71%)
    3 / 15 (20.00%)
    2 / 11 (18.18%)
    6 / 8 (75.00%)
    16 / 48 (33.33%)
         occurrences all number
    5
    4
    2
    8
    19
    DYSPHONIA
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    3 / 48 (6.25%)
         occurrences all number
    0
    1
    1
    1
    3
    DYSPNOEA
         subjects affected / exposed
    5 / 14 (35.71%)
    3 / 15 (20.00%)
    1 / 11 (9.09%)
    2 / 8 (25.00%)
    11 / 48 (22.92%)
         occurrences all number
    5
    4
    1
    2
    12
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    1
    0
    1
    0
    2
    EPISTAXIS
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    2
    0
    0
    2
    HAEMOPTYSIS
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    1
    1
    0
    0
    2
    HICCUPS
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences all number
    0
    1
    0
    1
    2
    HYPOXIA
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    2
    0
    0
    0
    2
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    1
    0
    1
    0
    2
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    1
    1
    0
    0
    2
    PLEURISY
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    PNEUMONITIS
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    2
    0
    0
    0
    2
    PRODUCTIVE COUGH
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    4 / 8 (50.00%)
    5 / 48 (10.42%)
         occurrences all number
    1
    0
    0
    4
    5
    RESPIRATORY TRACT CONGESTION
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    RHINITIS ALLERGIC
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    RHINORRHOEA
         subjects affected / exposed
    0 / 14 (0.00%)
    3 / 15 (20.00%)
    0 / 11 (0.00%)
    3 / 8 (37.50%)
    6 / 48 (12.50%)
         occurrences all number
    0
    3
    0
    3
    6
    SPUTUM DISCOLOURED
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    1
    1
    0
    2
    DEPRESSED MOOD
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    DEPRESSION
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    3 / 48 (6.25%)
         occurrences all number
    1
    0
    1
    1
    3
    INSOMNIA
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    2
    0
    0
    2
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    1
    1
    0
    0
    2
    AMYLASE INCREASED
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    3 / 48 (6.25%)
         occurrences all number
    0
    1
    2
    1
    4
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 15 (13.33%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    4 / 48 (8.33%)
         occurrences all number
    1
    2
    0
    1
    4
    BILIRUBIN CONJUGATED INCREASED
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    2
    0
    0
    2
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    3
    3
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences all number
    0
    2
    0
    1
    3
    BLOOD CHOLESTEROL INCREASED
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    BLOOD CREATINE INCREASED
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    4 / 48 (8.33%)
         occurrences all number
    2
    2
    0
    1
    5
    ELECTROCARDIOGRAM QT PROLONGED
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences all number
    1
    0
    0
    1
    2
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    LIPASE INCREASED
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    LYMPHOCYTE COUNT DECREASED
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    TROPONIN I INCREASED
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    TROPONIN INCREASED
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    WEIGHT DECREASED
         subjects affected / exposed
    7 / 14 (50.00%)
    8 / 15 (53.33%)
    5 / 11 (45.45%)
    3 / 8 (37.50%)
    23 / 48 (47.92%)
         occurrences all number
    7
    10
    6
    3
    26
    Injury, poisoning and procedural complications
    INFUSION RELATED REACTION
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    SCRATCH
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    STOMA SITE HAEMORRHAGE
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    ATRIOVENTRICULAR BLOCK FIRST DEGREE
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    CARDIAC FAILURE CONGESTIVE
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    SINUS BRADYCARDIA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    1
    0
    1
    0
    2
    SINUS TACHYCARDIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    TACHYCARDIA
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    2
    0
    0
    2
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    2 / 11 (18.18%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    0
    2
    0
    2
    DYSGEUSIA
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    2 / 11 (18.18%)
    0 / 8 (0.00%)
    4 / 48 (8.33%)
         occurrences all number
    1
    1
    2
    0
    4
    HEADACHE
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    3
    0
    0
    3
    LETHARGY
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences all number
    1
    0
    0
    1
    2
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    POLYNEUROPATHY
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    SOMNOLENCE
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences all number
    1
    0
    0
    1
    2
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    4 / 14 (28.57%)
    0 / 15 (0.00%)
    2 / 11 (18.18%)
    2 / 8 (25.00%)
    8 / 48 (16.67%)
         occurrences all number
    5
    0
    2
    3
    10
    LEUKOCYTOSIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    NEUTROPENIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    PANCYTOPENIA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    Ear and labyrinth disorders
    EAR PAIN
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    Eye disorders
    DRY EYE
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    EYE DISCHARGE
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    VISION BLURRED
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    1
    1
    0
    2
    Gastrointestinal disorders
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    ABDOMINAL PAIN
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    3 / 48 (6.25%)
         occurrences all number
    1
    0
    3
    1
    5
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    3 / 48 (6.25%)
         occurrences all number
    2
    0
    0
    1
    3
    ASCITES
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    CHEILITIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    2
    0
    0
    0
    2
    CONSTIPATION
         subjects affected / exposed
    1 / 14 (7.14%)
    4 / 15 (26.67%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    6 / 48 (12.50%)
         occurrences all number
    1
    10
    0
    1
    12
    DIARRHOEA
         subjects affected / exposed
    12 / 14 (85.71%)
    12 / 15 (80.00%)
    10 / 11 (90.91%)
    8 / 8 (100.00%)
    42 / 48 (87.50%)
         occurrences all number
    21
    22
    29
    12
    84
    DRY MOUTH
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    DYSPEPSIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences all number
    0
    0
    1
    1
    2
    DYSPHAGIA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    3 / 8 (37.50%)
    4 / 48 (8.33%)
         occurrences all number
    1
    0
    0
    3
    4
    GASTRITIS EROSIVE
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    3 / 48 (6.25%)
         occurrences all number
    0
    1
    0
    2
    3
    GINGIVAL PAIN
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    GLOSSODYNIA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    HAEMORRHOIDS
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    2 / 11 (18.18%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    0
    2
    0
    2
    LIP PAIN
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    MEGACOLON
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    NAUSEA
         subjects affected / exposed
    4 / 14 (28.57%)
    3 / 15 (20.00%)
    3 / 11 (27.27%)
    4 / 8 (50.00%)
    14 / 48 (29.17%)
         occurrences all number
    4
    3
    4
    5
    16
    OESOPHAGEAL ACHALASIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    OESOPHAGEAL PAIN
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    2
    2
    PROCTALGIA
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    STOMATITIS
         subjects affected / exposed
    6 / 14 (42.86%)
    6 / 15 (40.00%)
    5 / 11 (45.45%)
    3 / 8 (37.50%)
    20 / 48 (41.67%)
         occurrences all number
    6
    6
    5
    3
    20
    TOOTHACHE
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    VOMITING
         subjects affected / exposed
    5 / 14 (35.71%)
    3 / 15 (20.00%)
    3 / 11 (27.27%)
    2 / 8 (25.00%)
    13 / 48 (27.08%)
         occurrences all number
    6
    3
    4
    2
    15
    Hepatobiliary disorders
    HYPERBILIRUBINAEMIA
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    DECUBITUS ULCER
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    DERMATITIS ACNEIFORM
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    3
    0
    0
    0
    3
    DRY SKIN
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    2 / 11 (18.18%)
    2 / 8 (25.00%)
    6 / 48 (12.50%)
         occurrences all number
    1
    1
    2
    2
    6
    ECCHYMOSIS
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    ECZEMA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    0
    0
    2
    2
    ERYTHEMA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    0
    0
    2
    2
    NAIL TOXICITY
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    PETECHIAE
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    2
    0
    2
    PRURIGO
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    PRURITUS
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    2
    0
    3
    0
    5
    RASH
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    5 / 48 (10.42%)
         occurrences all number
    3
    0
    1
    1
    5
    RASH ERYTHEMATOUS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    1
    0
    1
    0
    2
    RASH MACULAR
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    1
    0
    1
    0
    2
    RASH MACULO-PAPULAR
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    2
    0
    0
    0
    2
    RASH PAPULAR
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    SKIN HYPOPIGMENTATION
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    SKIN LESION
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    SKIN REACTION
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    SKIN ULCER
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    Renal and urinary disorders
    CHRONIC KIDNEY DISEASE
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    HAEMATURIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    POLLAKIURIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    URETHRAL PAIN
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    URINARY TRACT PAIN
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    Endocrine disorders
    HYPOTHYROIDISM
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 15 (13.33%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    1
    2
    0
    0
    3
    FLANK PAIN
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    JOINT SWELLING
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    MUSCLE SPASMS
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    2 / 11 (18.18%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    0
    2
    0
    2
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    2 / 11 (18.18%)
    0 / 8 (0.00%)
    3 / 48 (6.25%)
         occurrences all number
    0
    1
    2
    0
    3
    MYOFASCIAL PAIN SYNDROME
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    NECK PAIN
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    Infections and infestations
    ANGULAR CHEILITIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    BACTERAEMIA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    BRONCHITIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    1
    0
    1
    0
    2
    CELLULITIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    HERPES ZOSTER
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    LICE INFESTATION
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    LIVER ABSCESS
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    LUNG INFECTION
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    NASOPHARYNGITIS
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    ONYCHOMYCOSIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    ORAL CANDIDIASIS
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    4 / 48 (8.33%)
         occurrences all number
    2
    0
    0
    2
    4
    OSTEOMYELITIS
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    1
    0
    1
    PARONYCHIA
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences all number
    0
    1
    0
    1
    2
    RASH PUSTULAR
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    SINUSITIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    URETHRITIS
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    0
    1
    0
    0
    1
    URINARY TRACT INFECTION
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    3
    0
    0
    0
    3
    VULVOVAGINAL CANDIDIASIS
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    11 / 14 (78.57%)
    8 / 15 (53.33%)
    6 / 11 (54.55%)
    6 / 8 (75.00%)
    31 / 48 (64.58%)
         occurrences all number
    12
    10
    6
    6
    34
    DEHYDRATION
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    2 / 11 (18.18%)
    1 / 8 (12.50%)
    5 / 48 (10.42%)
         occurrences all number
    2
    1
    2
    2
    7
    HYPERCALCAEMIA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    1 / 11 (9.09%)
    2 / 8 (25.00%)
    4 / 48 (8.33%)
         occurrences all number
    1
    0
    1
    2
    4
    HYPERGLYCAEMIA
         subjects affected / exposed
    8 / 14 (57.14%)
    6 / 15 (40.00%)
    5 / 11 (45.45%)
    4 / 8 (50.00%)
    23 / 48 (47.92%)
         occurrences all number
    16
    14
    9
    9
    48
    HYPERTRIGLYCERIDAEMIA
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 48 (2.08%)
         occurrences all number
    0
    0
    0
    1
    1
    HYPERURICAEMIA
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    0
    0
    0
    1
    HYPOALBUMINAEMIA
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 15 (13.33%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    5 / 48 (10.42%)
         occurrences all number
    1
    2
    0
    2
    5
    HYPOCALCAEMIA
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    4 / 48 (8.33%)
         occurrences all number
    3
    1
    4
    1
    9
    HYPOKALAEMIA
         subjects affected / exposed
    3 / 14 (21.43%)
    2 / 15 (13.33%)
    1 / 11 (9.09%)
    2 / 8 (25.00%)
    8 / 48 (16.67%)
         occurrences all number
    6
    2
    4
    5
    17
    HYPOMAGNESAEMIA
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 15 (13.33%)
    1 / 11 (9.09%)
    2 / 8 (25.00%)
    7 / 48 (14.58%)
         occurrences all number
    3
    2
    3
    3
    11
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    2 / 48 (4.17%)
         occurrences all number
    0
    1
    0
    3
    4
    HYPOPHAGIA
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    2
    0
    0
    0
    2
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    2 / 11 (18.18%)
    4 / 8 (50.00%)
    8 / 48 (16.67%)
         occurrences all number
    2
    0
    6
    6
    14
    METABOLIC ACIDOSIS
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    1
    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
    03 May 2013
    This amendment clarified that LJM716 and alpelisib will not be dose escalated beyond the MTD determined in the monotherapy Phase I studies.
    27 Jan 2014
    The purpose of this amendment was to include ophthalmologic assessments (at the request of a health authority).
    17 Dec 2014
    The purpose of this amendment was to include guidelines for management of pneumonitis.

    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.
    The phase 2 part was not conducted as the study was terminated early due to limited anti-tumor activity with LJM716-alpelisib combination observed in phase 1b.
    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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