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    Clinical Trial Results:
    Phase Ib dose finding study of abiraterone acetate plus BEZ235 or BKM120 in patients with castration-resistant prostate cancer 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
    2012-002250-23
    Trial protocol
    ES  
    Global end of trial date
    01 Jul 2015

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

    Trial information

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    Trial identification
    Sponsor protocol code
    CBEZ235D2101
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01634061
    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
    01 Jun 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Jul 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Dose escalation part: To determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of abiraterone acetate (AA) plus BEZ235 (twice a day) and AA plus BKM120 (once a day) in castration resistant prostate cancer (CRPC) patients with AA failure.
    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 Sep 2012
    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
    Spain: 8
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    United States: 2
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    Canada: 8
    Country: Number of subjects enrolled
    France: 12
    Worldwide total number of subjects
    43
    EEA total number of subjects
    33
    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)
    11
    From 65 to 84 years
    32
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 54 patients were screened for the study and 11 of them were screen failures out of which there were two missing screen failure patients for whom no data was entered in the database.

    Period 1
    Period 1 title
    Dose Escalation (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
    BEZ235 200mg bid + AA 1000mg qd
    Arm description
    BEZ235 200mg bid + Abiraterone Acetate (AA) 1000mg qd
    Arm type
    Experimental

    Investigational medicinal product name
    BEZ235
    Investigational medicinal product code
    BEZ235
    Other name
    dactosilib
    Pharmaceutical forms
    Dispersion, Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    BEZ235 was supplied at dose strengths of 50 mg, 100 mg, 200 mg, 300 mg and 400 mg solid dispersion sachets (SDS) for oral use twice a day for 28 days

    Investigational medicinal product name
    Abiraterone acetate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Abiraterone acetate (AA) 1000mg tablet for oral use once a day for 28 days

    Arm title
    BKM120 60mg qd + AA 1000mg qd
    Arm description
    BKM120 60mg qd + AA 1000mg qd
    Arm type
    Experimental

    Investigational medicinal product name
    BKM120
    Investigational medicinal product code
    BKM120
    Other name
    buparlisib
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    BKM120 was supplied at dose strengths of 10 mg and 50 mg hard gelatin capsules total of 60mg daily given orally for 28 days.

    Investigational medicinal product name
    Abiraterone acetate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Abiraterone acetate (AA) 1000mg tablet for oral use once a day for 28 days

    Arm title
    BKM120 100mg qd + AA 1000mg qd
    Arm description
    BKM120 100mg qd + AA 1000mg qd
    Arm type
    Experimental

    Investigational medicinal product name
    BKM120
    Investigational medicinal product code
    BKM120
    Other name
    buparlisib
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    BKM120 was supplied at dose strengths of 10 mg and 50 mg hard gelatin capsules total of 100mg daily given orally for 28 days.

    Investigational medicinal product name
    Abiraterone acetate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Abiraterone acetate (AA) 1000mg tablet for oral use once a day for 28 days

    Number of subjects in period 1
    BEZ235 200mg bid + AA 1000mg qd BKM120 60mg qd + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd
    Started
    18
    5
    20
    Completed
    0
    0
    0
    Not completed
    18
    5
    20
         subject/guardian decision
    5
    3
    3
         Adverse event, non-fatal
    9
    -
    7
         progressive disease
    4
    2
    10

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    BEZ235 200mg bid + AA 1000mg qd
    Reporting group description
    BEZ235 200mg bid + Abiraterone Acetate (AA) 1000mg qd

    Reporting group title
    BKM120 60mg qd + AA 1000mg qd
    Reporting group description
    BKM120 60mg qd + AA 1000mg qd

    Reporting group title
    BKM120 100mg qd + AA 1000mg qd
    Reporting group description
    BKM120 100mg qd + AA 1000mg qd

    Reporting group values
    BEZ235 200mg bid + AA 1000mg qd BKM120 60mg qd + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd Total
    Number of subjects
    18 5 20 43
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    4 0 7 11
        From 65-84 years
    14 5 13 32
        85 years and over
    0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    69.3 ( 7.58 ) 71.4 ( 7.86 ) 66.8 ( 7.38 ) -
    Gender categorical
    Units: Subjects
        Female
    0 0 0 0
        Male
    18 5 20 43

    End points

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    End points reporting groups
    Reporting group title
    BEZ235 200mg bid + AA 1000mg qd
    Reporting group description
    BEZ235 200mg bid + Abiraterone Acetate (AA) 1000mg qd

    Reporting group title
    BKM120 60mg qd + AA 1000mg qd
    Reporting group description
    BKM120 60mg qd + AA 1000mg qd

    Reporting group title
    BKM120 100mg qd + AA 1000mg qd
    Reporting group description
    BKM120 100mg qd + AA 1000mg qd

    Primary: Maximum Therapeutic Dose (MTD) of Abiraterone acetate (AA) plus BEZ235 (twice a day) and AA plus

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    End point title
    Maximum Therapeutic Dose (MTD) of Abiraterone acetate (AA) plus BEZ235 (twice a day) and AA plus [1]
    End point description
    The MTD was not reached for all three arms. The dose escalation was stopped after cohort 3 at 200 mg twice a day due to challenging safety and tolerability profile of BEZ235. The dose escalation was stopped after cohort 4 at 100 mg once a day as the combination was considered not feasible due to substantially lower exposure of BKM120 in this combination compared to the single agent exposure. The Full Analysis Set (FAS) comprised of all patients who received at least one dose of study treatment. Patients were analyzed according to the starting dose (BEZ235 or BKM120) they received. For efficacy analyses, the FAS was used.
    End point type
    Primary
    End point timeframe
    12 weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No planned statistical analyses were done for this outcome measure.
    End point values
    BEZ235 200mg bid + AA 1000mg qd BKM120 60mg qd + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd
    Number of subjects analysed
    18 [2]
    5 [3]
    20 [4]
    Units: mg
        number (not applicable)
    999
    999
    999
    Notes
    [2] - MTD not determined
    [3] - MTD was not determined
    [4] - MTD was not determined
    No statistical analyses for this end point

    Secondary: Change in Prostate-Specific Antigen (PSA) from baseline at 12 weeks, by dose level, BKM120

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    End point title
    Change in Prostate-Specific Antigen (PSA) from baseline at 12 weeks, by dose level, BKM120 [5]
    End point description
    PSA change is defined as the change from baseline to the lowest PSA value at any time from the start of treatment. The Full Analysis Set (FAS) comprised of all patients who received at least one dose of study treatment. Patients were analyzed according to the starting dose BKM120 they received. For efficacy analyses, the FAS was used.
    End point type
    Secondary
    End point timeframe
    12 weeks
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No planned statistical analyses were done for this outcome measure.
    End point values
    BKM120 60mg qd + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd
    Number of subjects analysed
    5
    20
    Units: ng/mL
        arithmetic mean (standard deviation)
    350.91 ( 227.548 )
    369.62 ( 462.931 )
    No statistical analyses for this end point

    Secondary: Soft tissue best overall response, by dose level, BKM120 combination arm

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    End point title
    Soft tissue best overall response, by dose level, BKM120 combination arm [6]
    End point description
    Overall response rate: Complete response (CR) + Partial response (PR) The Full Analysis Set (FAS) comprised of all patients who received at least one dose of study treatment. Patients were analyzed according to the starting dose BKM120 they received. For efficacy analyses, the FAS was used.
    End point type
    Secondary
    End point timeframe
    12 weeks
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No planned statistical analyses were done for this outcome measure.
    End point values
    BKM120 60mg qd + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd
    Number of subjects analysed
    5
    20
    Units: participants
        number (confidence interval 95%)
    0 (0 to 52.2)
    0 (0 to 16.8)
    No statistical analyses for this end point

    Secondary: Progression based on Bone Lesion (Radiological), by dose level,

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    End point title
    Progression based on Bone Lesion (Radiological), by dose level, [7]
    End point description
    Progressive evaluation in bone per Investigator assessment and derived assessments based on PCWG2 guidelines were listed. The derived assessment categories were summarized (“progressive disease”, “no progression”, “unknown” and “not assessed”). The Full Analysis Set (FAS) comprised of all patients who received at least one dose of study treatment. Patients were analyzed according to the starting dose BKM120 they received. For efficacy analyses, the FAS was used.
    End point type
    Secondary
    End point timeframe
    12 weeks
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No planned statistical analyses were done for this outcome measure.
    End point values
    BKM120 60mg qd + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd
    Number of subjects analysed
    5
    20
    Units: participants
    number (not applicable)
        Progressive Disease (PD)
    1
    0
        Not progressed
    2
    9
        Not Assessed
    0
    0
        Unknown (UNK)
    2
    11
    No statistical analyses for this end point

    Secondary: Pharmacokinetic PK parameters Area Under Curve (AUCtau) at Cycle 1 Day 22, BKM120 combination arm

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    End point title
    Pharmacokinetic PK parameters Area Under Curve (AUCtau) at Cycle 1 Day 22, BKM120 combination arm [8]
    End point description
    AUCtau,ss Drug exposure over a dosing period, i.e. 12 hours for a BID regimen, 24 hours for QD, regimen. The pharmacokinetics of BKM120 were analyzed on Cycle 1 Day 22, based on the full PK profiles collected during the dose escalation part using the PAS set. Pharmacokinetic analysis set (PAS) consisted of patients who receive at least one dose of BKM120/BEZ235 or AA and have at least one non-missing and non-zero concentration measurement of BKM120/BEZ235 or AA.
    End point type
    Secondary
    End point timeframe
    Day 22
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No planned statistical analyses were done for this outcome measure.
    End point values
    BKM120 60mg qd + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd
    Number of subjects analysed
    5
    20
    Units: (h*ng/mL)
        arithmetic mean (standard deviation)
    6830 ( 1030 )
    15100 ( 3230 )
    No statistical analyses for this end point

    Secondary: Pharmacokinetic PK parameters Cmax at Cycle 1 Day 22, BKM120 combination arm

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    End point title
    Pharmacokinetic PK parameters Cmax at Cycle 1 Day 22, BKM120 combination arm [9]
    End point description
    Cmax,ss The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration at steady state (mass x volume-1) The pharmacokinetics of BKM120 were analyzed on Cycle 1 Day 22, based on the full PK profiles collected during the dose escalation part using the PAS set. Pharmacokinetic analysis set (PAS) consisted of patients who receive at least one dose of BKM120/BEZ235 or AA and have at least one non-missing and non-zero concentration measurement of BKM120/BEZ235 or AA.
    End point type
    Secondary
    End point timeframe
    Day 22
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No planned statistical analyses were done for this outcome measure.
    End point values
    BKM120 60mg qd + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd
    Number of subjects analysed
    5
    20
    Units: ng/mL
        arithmetic mean (standard deviation)
    599 ( 140 )
    1180 ( 423 )
    No statistical analyses for this end point

    Secondary: BKM120 PK parameters Tmax atCycle 1 Day 22, BKM120 combination arm

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    End point title
    BKM120 PK parameters Tmax atCycle 1 Day 22, BKM120 combination arm [10]
    End point description
    Tmax,ss The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration at steady state. The pharmacokinetics of BKM120 were analyzed on Cycle 1 Day 22, based on the full PK profiles collected during the dose escalation part using the PAS set. Pharmacokinetic analysis set (PAS) consisted of patients who receive at least one dose of BKM120/BEZ235 or AA and have at least one non-missing and non-zero concentration measurement of BKM120/BEZ235 or AA.
    End point type
    Secondary
    End point timeframe
    Day 22
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: MTD was not determined. No planned statistical analyses were done for this outcome measure.
    End point values
    BKM120 60mg qd + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd
    Number of subjects analysed
    5
    20
    Units: hours
        median (full range (min-max))
    2 (1.5 to 2.97)
    2.51 (0 to 6.08)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious Adverse Events are monitored from date of First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All other adverse events are monitored from First Patient First Treatment until Last Patient Last Visit
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    BEZ235 200mg bid + AA 1000mg qd
    Reporting group description
    BEZ235 200mg bid + AA 1000mg qd

    Reporting group title
    BKM120 100mg qd + AA 1000mg qd
    Reporting group description
    BKM120 100mg qd + AA 1000mg qd

    Reporting group title
    BKM120 60mg qd + AA 1000mg qd
    Reporting group description
    BKM120 60mg qd + AA 1000mg qd

    Serious adverse events
    BEZ235 200mg bid + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd BKM120 60mg qd + AA 1000mg qd
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 18 (55.56%)
    7 / 20 (35.00%)
    1 / 5 (20.00%)
         number of deaths (all causes)
    1
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    METASTASES TO CENTRAL NERVOUS SYSTEM
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    METASTASES TO SPINE
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    VENOUS THROMBOSIS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    HAEMORRHAGIC TRANSFORMATION STROKE
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    SPINAL CORD COMPRESSION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BONE MARROW FAILURE
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    DIARRHOEA
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    HEPATIC PAIN
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    RENAL FAILURE
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL IMPAIRMENT
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BONE PAIN
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PATHOLOGICAL FRACTURE
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMOCYSTIS JIROVECII PNEUMONIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    BEZ235 200mg bid + AA 1000mg qd BKM120 100mg qd + AA 1000mg qd BKM120 60mg qd + AA 1000mg qd
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 18 (100.00%)
    19 / 20 (95.00%)
    5 / 5 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    SEBORRHOEIC KERATOSIS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    Vascular disorders
    HOT FLUSH
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    2
    0
    1
    ORTHOSTATIC HYPERTENSION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    HYPERTENSION
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    0
    HYPOTENSION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    3 / 18 (16.67%)
    7 / 20 (35.00%)
    2 / 5 (40.00%)
         occurrences all number
    4
    9
    2
    CHILLS
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    0
    0
    FATIGUE
         subjects affected / exposed
    6 / 18 (33.33%)
    7 / 20 (35.00%)
    3 / 5 (60.00%)
         occurrences all number
    7
    8
    4
    FACE OEDEMA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    0
    1
    FEELING COLD
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    HYPERTHERMIA
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    0
    MALAISE
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    MUCOSAL DRYNESS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    PYREXIA
         subjects affected / exposed
    3 / 18 (16.67%)
    2 / 20 (10.00%)
    0 / 5 (0.00%)
         occurrences all number
    5
    2
    0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    Reproductive system and breast disorders
    TESTICULAR PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    PELVIC PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    ERECTILE DYSFUNCTION
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    2
    1
    EPISTAXIS
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    2 / 5 (40.00%)
         occurrences all number
    0
    0
    2
    DYSPNOEA
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 20 (10.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    2
    0
    DYSPHONIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    PHARYNGEAL ULCERATION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    HICCUPS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    PHARYNGEAL ERYTHEMA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    SINUS CONGESTION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    PNEUMONITIS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    Psychiatric disorders
    AGITATION
         subjects affected / exposed
    2 / 18 (11.11%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    1
    0
    CONFUSIONAL STATE
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    INSOMNIA
         subjects affected / exposed
    2 / 18 (11.11%)
    1 / 20 (5.00%)
    2 / 5 (40.00%)
         occurrences all number
    2
    1
    2
    DEPRESSED MOOD
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 20 (10.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    2
    0
    DEPRESSION
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    1
    1
    IRRITABILITY
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    1
    MOOD ALTERED
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 20 (10.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    2
    0
    SLEEP DISORDER
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    Investigations
    AMYLASE INCREASED
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    1
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    1
    0
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    0
    0
    GLYCOSYLATED HAEMOGLOBIN INCREASED
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    INSULIN C-PEPTIDE INCREASED
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    LIPASE INCREASED
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    2
    0
    LYMPHOCYTE COUNT DECREASED
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    1
    0
    PLATELET COUNT DECREASED
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    WEIGHT DECREASED
         subjects affected / exposed
    5 / 18 (27.78%)
    5 / 20 (25.00%)
    0 / 5 (0.00%)
         occurrences all number
    6
    5
    0
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    Injury, poisoning and procedural complications
    CONTUSION
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    FALL
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    INJURY
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    Cardiac disorders
    PALPITATIONS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    BRADYCARDIA
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    0
    VENTRICULAR EXTRASYSTOLES
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    Nervous system disorders
    DYSGEUSIA
         subjects affected / exposed
    3 / 18 (16.67%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    3
    1
    0
    DIZZINESS
         subjects affected / exposed
    2 / 18 (11.11%)
    3 / 20 (15.00%)
    1 / 5 (20.00%)
         occurrences all number
    2
    4
    1
    DYSKINESIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    PRESYNCOPE
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    1
    PARAESTHESIA
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 20 (10.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    2
    0
    EXTRAPYRAMIDAL DISORDER
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    0
    1
    HEADACHE
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 20 (10.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    3
    1
    SOMNOLENCE
         subjects affected / exposed
    1 / 18 (5.56%)
    3 / 20 (15.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    4
    0
    RESTLESS LEGS SYNDROME
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    TREMOR
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    VITH NERVE PARALYSIS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    3 / 18 (16.67%)
    6 / 20 (30.00%)
    0 / 5 (0.00%)
         occurrences all number
    5
    6
    0
    LYMPHOPENIA
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    0
    0
    THROMBOCYTOPENIA
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    3
    0
    0
    Ear and labyrinth disorders
    TINNITUS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    1
    VERTIGO
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    0
    1
    Eye disorders
    LACRIMATION INCREASED
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    1
    PHOTOPHOBIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    2
    0
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 20 (10.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    3
    0
    ABDOMINAL PAIN
         subjects affected / exposed
    3 / 18 (16.67%)
    4 / 20 (20.00%)
    0 / 5 (0.00%)
         occurrences all number
    5
    4
    0
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    0
    CHRONIC GASTRITIS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    CONSTIPATION
         subjects affected / exposed
    4 / 18 (22.22%)
    2 / 20 (10.00%)
    0 / 5 (0.00%)
         occurrences all number
    4
    2
    0
    DIARRHOEA
         subjects affected / exposed
    14 / 18 (77.78%)
    6 / 20 (30.00%)
    1 / 5 (20.00%)
         occurrences all number
    23
    12
    2
    DYSPEPSIA
         subjects affected / exposed
    2 / 18 (11.11%)
    3 / 20 (15.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    3
    0
    DRY MOUTH
         subjects affected / exposed
    3 / 18 (16.67%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    3
    1
    0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    1
    1
    FLATULENCE
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    HAEMATOCHEZIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    HAEMORRHOIDS
         subjects affected / exposed
    2 / 18 (11.11%)
    2 / 20 (10.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    2
    0
    NAUSEA
         subjects affected / exposed
    10 / 18 (55.56%)
    11 / 20 (55.00%)
    3 / 5 (60.00%)
         occurrences all number
    17
    16
    4
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    0
    1
    RECTAL TENESMUS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    REGURGITATION
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    STOMATITIS
         subjects affected / exposed
    7 / 18 (38.89%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    8
    0
    0
    TOOTHACHE
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    VOMITING
         subjects affected / exposed
    5 / 18 (27.78%)
    6 / 20 (30.00%)
    2 / 5 (40.00%)
         occurrences all number
    6
    7
    3
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    DRY SKIN
         subjects affected / exposed
    0 / 18 (0.00%)
    3 / 20 (15.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    3
    0
    BLISTER
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    DERMATITIS ACNEIFORM
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    HYPERHIDROSIS
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    0
    1
    ERYTHEMA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    2
    0
    NIGHT SWEATS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    RASH
         subjects affected / exposed
    1 / 18 (5.56%)
    4 / 20 (20.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    5
    0
    PHOTOSENSITIVITY REACTION
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    PRURITUS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    0
    1
    RASH ERYTHEMATOUS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    RASH PAPULAR
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    0
    SKIN DISORDER
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    URTICARIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    Renal and urinary disorders
    HAEMATURIA
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    0
    NOCTURIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    URINARY INCONTINENCE
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 18 (5.56%)
    3 / 20 (15.00%)
    2 / 5 (40.00%)
         occurrences all number
    1
    3
    2
    BACK PAIN
         subjects affected / exposed
    2 / 18 (11.11%)
    4 / 20 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    3
    7
    2
    BONE PAIN
         subjects affected / exposed
    3 / 18 (16.67%)
    3 / 20 (15.00%)
    0 / 5 (0.00%)
         occurrences all number
    4
    3
    0
    INTERVERTEBRAL DISC COMPRESSION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    FLANK PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    2
    0
    MUSCLE SPASMS
         subjects affected / exposed
    2 / 18 (11.11%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    2
    0
    MUSCULAR WEAKNESS
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    2
    0
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    2 / 18 (11.11%)
    1 / 20 (5.00%)
    2 / 5 (40.00%)
         occurrences all number
    2
    1
    2
    MUSCULOSKELETAL DISCOMFORT
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    MYALGIA
         subjects affected / exposed
    4 / 18 (22.22%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    4
    1
    0
    PAIN IN EXTREMITY
         subjects affected / exposed
    4 / 18 (22.22%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    5
    2
    0
    MYOPATHY
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    NECK PAIN
         subjects affected / exposed
    2 / 18 (11.11%)
    3 / 20 (15.00%)
    1 / 5 (20.00%)
         occurrences all number
    2
    3
    1
    PAIN IN JAW
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    SPINAL PAIN
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    ABSCESS LIMB
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    CYSTITIS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    CONJUNCTIVITIS
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    0
    0
    OSTEOMYELITIS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    ESCHERICHIA URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    GASTROENTERITIS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    NASOPHARYNGITIS
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    RHINITIS
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    URINARY TRACT INFECTION
         subjects affected / exposed
    2 / 18 (11.11%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    1
    0
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    5 / 18 (27.78%)
    9 / 20 (45.00%)
    1 / 5 (20.00%)
         occurrences all number
    5
    10
    1
    DEHYDRATION
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    FLUID OVERLOAD
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    HYPERGLYCAEMIA
         subjects affected / exposed
    4 / 18 (22.22%)
    9 / 20 (45.00%)
    2 / 5 (40.00%)
         occurrences all number
    6
    17
    3
    HYPERKALAEMIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    HYPERTRIGLYCERIDAEMIA
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    0
    HYPOCALCAEMIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    HYPOALBUMINAEMIA
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    0
    HYPOKALAEMIA
         subjects affected / exposed
    3 / 18 (16.67%)
    4 / 20 (20.00%)
    2 / 5 (40.00%)
         occurrences all number
    3
    5
    2
    IRON DEFICIENCY
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    HYPOMAGNESAEMIA
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 20 (10.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    2
    0
    METABOLIC ACIDOSIS
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Apr 2013
    Amendment 1: The main purpose of this amendment is to provide clarification and guidance to the investigators on the management of BKM120 and BEZ235 related toxicities. These include modifications to the management of psychiatric disorders, hyperglycemia, stomatitis, and rash. The changes also include the time of meals and dosing relative to pharmacokinetic sampling.

    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.
    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.
    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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