Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43862   clinical trials with a EudraCT protocol, of which   7285   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A phase I, multi-center, open-label study of LEE011 in patients with malignant rhabdoid tumors and neuroblastoma

    Summary
    EudraCT number
    		 2012-004228-40
    Trial protocol
    		 GB   FR  
    Global end of trial date
    29 Jun 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Dec 2017
    First version publication date
    23 Dec 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CLEE011X2102
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01747876
    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, novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma, AG, 41 613241111, novartis.email@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Jun 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jun 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective was to estimate the maximum tolerated dose (MTD) and/or the recommended expansion dose (RDE) of LEE011 when administered orally as a single agent in pediatric 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
    28 May 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    United States: 15
    Worldwide total number of subjects
    32
    EEA total number of subjects
    16
    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)
    3
    Children (2-11 years)
    19
    Adolescents (12-17 years)
    7
    Adults (18-64 years)
    3
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Approximately 64 patients were to be treated during the entire study; however, 32 patients were enrolled and treated at the time of the enrollment halt.

    Pre-assignment
    Screening details
    		 The escalation part of the study explored the 3 doses 280, 350 & 470 mg/m2) in successive cohorts. The dose expansion phase of the study was not conducted (due to enrollment halt).

    Period 1
    Period 1 title
    Overall Study (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
    		 LEE011 280 mg/m2 - Dose Escalation only
    Arm description
    		 Patients who took 280 mg/m2 of LEE011. The dose escalation part of the study explored the 3 doses (280, 350 & 470 mg/m2) in successive cohorts.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LEE011
    Investigational medicinal product code
    LEE011
    Other name
    Pharmaceutical forms
    Powder for oral suspension, Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Three formulations for oral use: Capsules (10 mg, 50 mg, and 200 mg dose strength), powder in bottle (1200 mg in 125 mL amber bottles), and liquid formulation, which was not explored due to early enrollment halt.

    Arm title
    		 LEE011 350 mg/m2 - Dose Escalation only
    Arm description
    		 Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study explored the 3 doses (280, 350 & 470 mg/m2) in successive cohorts.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LEE011
    Investigational medicinal product code
    LEE011
    Other name
    Pharmaceutical forms
    Capsule, Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Three formulations for oral use: Capsules (10 mg, 50 mg, and 200 mg dose strength), powder in bottle (1200 mg in 125 mL amber bottles), and liquid formulation, which was not explored due to early enrollment halt.

    Arm title
    		 LEE011 470 mg/m2 - Dose Escalation only
    Arm description
    		 Patients who took 470 mg/m2 of LEE011. The dose escalation part of the study explored the 3 doses (280, 350 & 470 mg/m2) in successive cohorts.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LEE011
    Investigational medicinal product code
    LEE011
    Other name
    Pharmaceutical forms
    Capsule, Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Three formulations for oral use: Capsules (10 mg, 50 mg, and 200 mg dose strength), powder in bottle (1200 mg in 125 mL amber bottles), and liquid formulation, which was not explored due to early enrollment halt.

    Number of subjects in period 1
    		LEE011 280 mg/m2 - Dose Escalation only LEE011 350 mg/m2 - Dose Escalation only LEE011 470 mg/m2 - Dose Escalation only
    Started
    5
    15
    12
    Completed
    0
    0
    0
    Not completed
    5
    15
    12
         Consent withdrawn by subject
    -
    1
    1
         Disease progression
    4
    13
    8
         Adverse event, non-fatal
    1
    -
    2
         Trtment duration compl. as per protocol
    -
    1
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    LEE011 280 mg/m2 - Dose Escalation only
    Reporting group description
    		 Patients who took 280 mg/m2 of LEE011. The dose escalation part of the study explored the 3 doses (280, 350 & 470 mg/m2) in successive cohorts.

    Reporting group title
    LEE011 350 mg/m2 - Dose Escalation only
    Reporting group description
    		 Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study explored the 3 doses (280, 350 & 470 mg/m2) in successive cohorts.

    Reporting group title
    LEE011 470 mg/m2 - Dose Escalation only
    Reporting group description
    		 Patients who took 470 mg/m2 of LEE011. The dose escalation part of the study explored the 3 doses (280, 350 & 470 mg/m2) in successive cohorts.

    Reporting group values
    		 LEE011 280 mg/m2 - Dose Escalation only LEE011 350 mg/m2 - Dose Escalation only LEE011 470 mg/m2 - Dose Escalation only Total
    Number of subjects
    		 5 15 12 32
    Age Categorical
    Units: Subjects
        Infants and toddlers (28 days - 23 months)
    		 2 0 1 3
        Children (2 - 11 years)
    		 2 10 7 19
        Adolescents (12 - 17 years)
    		 1 4 2 7
        Adults (18 - 64 years)
    		 0 1 2 3
    Gender, Male/Female
    Units: Subjects
        Female
    		 1 6 4 11
        Male
    		 4 9 8 21
    Race/Ethnicity
    Units: Subjects
        Caucasian
    		 1 10 9 20
        Not available
    		 4 5 3 12

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    LEE011 280 mg/m2 - Dose Escalation only
    Reporting group description
    		 Patients who took 280 mg/m2 of LEE011. The dose escalation part of the study explored the 3 doses (280, 350 & 470 mg/m2) in successive cohorts.

    Reporting group title
    LEE011 350 mg/m2 - Dose Escalation only
    Reporting group description
    		 Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study explored the 3 doses (280, 350 & 470 mg/m2) in successive cohorts.

    Reporting group title
    LEE011 470 mg/m2 - Dose Escalation only
    Reporting group description
    		 Patients who took 470 mg/m2 of LEE011. The dose escalation part of the study explored the 3 doses (280, 350 & 470 mg/m2) in successive cohorts.

    Subject analysis set title
    MRT group
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Patients had a confirmed diagnosis of malignant rhabdoid tumors

    Subject analysis set title
    Neuroblastoma (NB)
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Patients had a confirmed diagnosis of neuroblastoma.

    Primary: Incidence rate of dose limiting toxicities (DLTs) by primary system organ class, preferred term and treatment

    		 Close Top of page
    End point title
    		 Incidence rate of dose limiting toxicities (DLTs) by primary system organ class, preferred term and treatment [1]
    End point description
    A DLT was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment with LEE011 and met any of the predefined criteria. For the purpose of dose-escalation decisions, DLTs were considered and included in the Bayesian Logistic Regression Model (BLRM). Patients who did not experience DLT during the first cycle were considered to have had sufficient safety evaluations if they were observed for ≥ 28 days following the first dose and were considered to have had enough safety data to conclude that a DLT did not occur. Patients who did not meet these minimum safety evaluation requirements were regarded as ineligible for the DDS. A patient with multiple DLTs within a primary system organ class is counted only once in the total row.
    End point type
    Primary
    End point timeframe
    cycle 1 = 28 days (from the time of first dose)
    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 comparative statistical analysis was conducted for this endpoint. The relationship between dose and the probability of DLT was modelled using adaptive Bayesian logistic regression model with overdose control principle.
    End point values
    		 LEE011 280 mg/m2 - Dose Escalation only LEE011 350 mg/m2 - Dose Escalation only LEE011 470 mg/m2 - Dose Escalation only
    Number of subjects analysed
    5
    15
    10
    Units: Participants
        Any primary system organ class total
    1
    0
    2
        Blood & lymphatic sys. disorders(Thrombocytopenia)
    0
    0
    1
        Gen. disorders & admin. site conditions (fatigue)
    1
    0
    0
        Investigations (Platelet count decreased)
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Overall Response Rate

    		 Close Top of page
    End point title
    		 Overall Response Rate
    End point description
    This analysis was not done as there were no responders.
    End point type
    Secondary
    End point timeframe
    Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days
    End point values
    		 LEE011 280 mg/m2 - Dose Escalation only LEE011 350 mg/m2 - Dose Escalation only LEE011 470 mg/m2 - Dose Escalation only
    Number of subjects analysed
    5
    15
    12
    Units: months
        median (confidence interval 95%)
    0.0 (0.0 to 0.0)
    0.0 (0.0 to 0.0)
    0.0 (0.0 to 0.0)
    No statistical analyses for this end point

    Secondary: Time to disease progression (TTP) per RECIST 1.1

    		 Close Top of page
    End point title
    		 Time to disease progression (TTP) per RECIST 1.1
    End point description
    TTP was assessed per Investigator, for the MRT & neuroblastoma patients for the pooled MTD & RDE according to RECIST 1.1 criteria using Kaplan-Meier method. Time to progression (TTP) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient has not had an event, time to progression is censored at the date of last adequate tumor assessment.
    End point type
    Secondary
    End point timeframe
    Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days
    End point values
    		 MRT group Neuroblastoma (NB)
    Number of subjects analysed
    11
    14
    Units: months
        median (confidence interval 95%)
    1.8 (1.7 to 2.0)
    1.8 (1.7 to 4.4)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

    		 Close Top of page
    End point title
    		 Duration of Response (DOR)
    End point description
    Assess the anti-tumor activity of LEE011 by RECIST 1.1. DOR was not assessed.
    End point type
    Secondary
    End point timeframe
    Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days
    End point values
    		 LEE011 280 mg/m2 - Dose Escalation only LEE011 350 mg/m2 - Dose Escalation only LEE011 470 mg/m2 - Dose Escalation only
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    Units: weeks
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [2] - Due to halted enrollment &/lack of CR & PR, analysis wasn’t performed for DOR during dose-escalation
    [3] - Due to halted enrollment &/lack of CR & PR, analysis wasn’t performed for DOR during dose-escalation
    [4] - Due to halted enrollment &/lack of CR & PR, analysis wasn’t performed for DOR during dose-escalation
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK) parameter: AUC0-24

    		 Close Top of page
    End point title
    		 Pharmacokinetics (PK) parameter: AUC0-24
    End point description
    The AUC calculated to the end of a dosing interval (tau) following single dose or at steady-state (amount x time x volume-1). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (C1D1), Cycle 1 Day 15 (C1D15)
    End point values
    		 LEE011 280 mg/m2 - Dose Escalation only LEE011 350 mg/m2 - Dose Escalation only LEE011 470 mg/m2 - Dose Escalation only
    Number of subjects analysed
    5
    12
    7
    Units: h*ng/ml
    median (full range (min-max))
        C1D1 (n = 5, 12, 7)
    9250 (4580 to 22000)
    10000 (5320 to 43600)
    17600 (8010 to 28500)
        C1D15 (n = 3, 7, 5)
    13800 (8910 to 60100)
    24500 (15100 to 60100)
    29100 (13300 to 50500)
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK) parameter: Cmax

    		 Close Top of page
    End point title
    		 Pharmacokinetics (PK) parameter: Cmax
    End point description
    Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration or at steady-state (mass x volume-1). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin
    End point type
    Secondary
    End point timeframe
    C1D1, C1D15
    End point values
    		 LEE011 280 mg/m2 - Dose Escalation only LEE011 350 mg/m2 - Dose Escalation only LEE011 470 mg/m2 - Dose Escalation only
    Number of subjects analysed
    5
    12
    10
    Units: ng/ml
    median (full range (min-max))
        C1D1 (n = 5, 12, 7)
    937 (542 to 1910)
    1130 (514 to 4140)
    1960 (796 to 4360)
        C1D1 (n = 4, 12,10)
    1110 (860 to 5210)
    2010 (633 to 4270)
    2500 (562 to 5050)
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK) parameter: Tmax

    		 Close Top of page
    End point title
    		 Pharmacokinetics (PK) parameter: Tmax
    End point description
    Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration or at steady-state (time). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin.
    End point type
    Secondary
    End point timeframe
    C1D1, C1D15
    End point values
    		 LEE011 280 mg/m2 - Dose Escalation only LEE011 350 mg/m2 - Dose Escalation only LEE011 470 mg/m2 - Dose Escalation only
    Number of subjects analysed
    5
    12
    10
    Units: hour
    median (full range (min-max))
        C1D1 (n = 5, 12, 7)
    2.03 (1.1 to 4.08)
    2.02 (1 to 4.05)
    4 (2 to 4.07)
        C1D15 (n = 4, 12, 10)
    2.08 (1.13 to 3.83)
    2.13 (1.08 to 23.8)
    3.92 (1.98 to 23.6)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Timeframe for AE
    Adverse event reporting additional description
    AE additional description
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    LEE011@280 mg/m2
    Reporting group description
    		 LEE011@280 mg/m2

    Reporting group title
    LEE011@350 mg/m2
    Reporting group description
    		 LEE011@350 mg/m2

    Reporting group title
    LEE011@470 mg/m2
    Reporting group description
    		 LEE011@470 mg/m2

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

    Serious adverse events
    		 LEE011@280 mg/m2 LEE011@350 mg/m2 LEE011@470 mg/m2 All@patients
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 5 (60.00%)
    7 / 15 (46.67%)
    4 / 12 (33.33%)
    14 / 32 (43.75%)
         number of deaths (all causes)
    2
    2
    1
    5
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Central nervous system neuroblastoma
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Face oedema
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Apnoea
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extrapyramidal disorder
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile convulsion
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    2 / 12 (16.67%)
    2 / 32 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial pressure increased
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Seizure
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Orbital oedema
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Polyuria
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Device related infection
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal bacteraemia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal infection
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polydipsia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 LEE011@280 mg/m2 LEE011@350 mg/m2 LEE011@470 mg/m2 All@patients
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 5 (100.00%)
    15 / 15 (100.00%)
    12 / 12 (100.00%)
    32 / 32 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to meninges
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    0
    0
    1
    Tumour pain
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    Hypotension
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    1 / 12 (8.33%)
    3 / 32 (9.38%)
         occurrences all number
    0
    2
    2
    4
    Raynaud's phenomenon
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    0
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 5 (0.00%)
    5 / 15 (33.33%)
    1 / 12 (8.33%)
    6 / 32 (18.75%)
         occurrences all number
    0
    5
    1
    6
    Catheter site pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Chills
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Complication associated with device
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Drug intolerance
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Face oedema
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Fatigue
         subjects affected / exposed
    1 / 5 (20.00%)
    5 / 15 (33.33%)
    6 / 12 (50.00%)
    12 / 32 (37.50%)
         occurrences all number
    1
    6
    7
    14
    Gait disturbance
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    3 / 32 (9.38%)
         occurrences all number
    1
    1
    1
    3
    Malaise
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    Pain
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 15 (6.67%)
    2 / 12 (16.67%)
    4 / 32 (12.50%)
         occurrences all number
    1
    1
    2
    4
    Pyrexia
         subjects affected / exposed
    1 / 5 (20.00%)
    5 / 15 (33.33%)
    2 / 12 (16.67%)
    8 / 32 (25.00%)
         occurrences all number
    2
    6
    3
    11
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Reproductive system and breast disorders
    Menstruation irregular
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Oedema genital
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Apnoea
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    2
    0
    2
    Bradypnoea
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    Cough
         subjects affected / exposed
    0 / 5 (0.00%)
    6 / 15 (40.00%)
    3 / 12 (25.00%)
    9 / 32 (28.13%)
         occurrences all number
    0
    9
    3
    12
    Dysphonia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Dyspnoea
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    2
    0
    2
    Epistaxis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    3 / 12 (25.00%)
    3 / 32 (9.38%)
         occurrences all number
    0
    0
    3
    3
    Hypoxia
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    1
    2
    0
    3
    Nasal congestion
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    3
    0
    3
    Oropharyngeal pain
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    1 / 12 (8.33%)
    3 / 32 (9.38%)
         occurrences all number
    0
    7
    1
    8
    Respiratory distress
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    2
    0
    2
    Rhinorrhoea
         subjects affected / exposed
    0 / 5 (0.00%)
    3 / 15 (20.00%)
    3 / 12 (25.00%)
    6 / 32 (18.75%)
         occurrences all number
    0
    7
    3
    10
    Sneezing
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    2
    0
    2
    Tachypnoea
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    3
    0
    3
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    2
    0
    2
    Agitation
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 15 (13.33%)
    2 / 12 (16.67%)
    5 / 32 (15.63%)
         occurrences all number
    1
    2
    2
    5
    Anxiety
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    2
    0
    2
    Depressed mood
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Insomnia
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 15 (6.67%)
    2 / 12 (16.67%)
    4 / 32 (12.50%)
         occurrences all number
    1
    1
    2
    4
    Irritability
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Mood altered
         subjects affected / exposed
    2 / 5 (40.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    2
    0
    0
    2
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 5 (0.00%)
    3 / 15 (20.00%)
    2 / 12 (16.67%)
    5 / 32 (15.63%)
         occurrences all number
    0
    7
    2
    9
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 5 (0.00%)
    5 / 15 (33.33%)
    4 / 12 (33.33%)
    9 / 32 (28.13%)
         occurrences all number
    0
    7
    6
    13
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    Blood bilirubin increased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    2
    2
    4
    Blood creatinine decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    0 / 5 (0.00%)
    5 / 15 (33.33%)
    2 / 12 (16.67%)
    7 / 32 (21.88%)
         occurrences all number
    0
    7
    3
    10
    Blood lactate dehydrogenase decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    2
    0
    2
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    2
    0
    2
    Blood potassium decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    2
    0
    2
    Blood sodium decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Blood urea increased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 5 (0.00%)
    4 / 15 (26.67%)
    3 / 12 (25.00%)
    7 / 32 (21.88%)
         occurrences all number
    0
    9
    4
    13
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    3
    0
    3
    Heart rate increased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    5 / 15 (33.33%)
    5 / 12 (41.67%)
    10 / 32 (31.25%)
         occurrences all number
    0
    8
    11
    19
    Neutrophil count decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    10 / 15 (66.67%)
    5 / 12 (41.67%)
    15 / 32 (46.88%)
         occurrences all number
    0
    35
    10
    45
    Platelet count decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    7 / 15 (46.67%)
    5 / 12 (41.67%)
    12 / 32 (37.50%)
         occurrences all number
    0
    11
    7
    18
    Weight decreased
         subjects affected / exposed
    1 / 5 (20.00%)
    4 / 15 (26.67%)
    1 / 12 (8.33%)
    6 / 32 (18.75%)
         occurrences all number
    1
    4
    1
    6
    Weight increased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    White blood cell count decreased
         subjects affected / exposed
    1 / 5 (20.00%)
    11 / 15 (73.33%)
    9 / 12 (75.00%)
    21 / 32 (65.63%)
         occurrences all number
    2
    21
    12
    35
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    0
    0
    1
    Contusion
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    4 / 12 (33.33%)
    6 / 32 (18.75%)
         occurrences all number
    0
    2
    4
    6
    Fall
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    2
    0
    2
    Laceration
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    2
    0
    2
    Ligament sprain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Procedural pain
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    Radiation skin injury
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Scratch
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    3 / 32 (9.38%)
         occurrences all number
    1
    2
    0
    3
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Sinus tachycardia
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    3 / 32 (9.38%)
         occurrences all number
    1
    2
    1
    4
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Brain oedema
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    0
    0
    1
    Dizziness
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    3 / 32 (9.38%)
         occurrences all number
    2
    2
    0
    4
    Dysgeusia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    0
    0
    1
    Extrapyramidal disorder
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Headache
         subjects affected / exposed
    3 / 5 (60.00%)
    7 / 15 (46.67%)
    5 / 12 (41.67%)
    15 / 32 (46.88%)
         occurrences all number
    3
    8
    6
    17
    Hydrocephalus
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    IIIrd nerve disorder
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Lethargy
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Monoplegia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    0
    0
    1
    Somnolence
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    1
    1
    0
    2
    Syncope
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Tremor
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    3
    0
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 5 (20.00%)
    8 / 15 (53.33%)
    6 / 12 (50.00%)
    15 / 32 (46.88%)
         occurrences all number
    1
    12
    11
    24
    Haemolysis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Leukopenia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Lymphopenia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    2
    3
    Neutropenia
         subjects affected / exposed
    2 / 5 (40.00%)
    3 / 15 (20.00%)
    3 / 12 (25.00%)
    8 / 32 (25.00%)
         occurrences all number
    2
    4
    15
    21
    Thrombocytopenia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    3 / 12 (25.00%)
    4 / 32 (12.50%)
         occurrences all number
    0
    1
    4
    5
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Ear pain
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    External ear inflammation
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    External ear pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Hypoacusis
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    2
    0
    2
    Middle ear inflammation
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Eye discharge
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    3
    0
    3
    Eyelid haematoma
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Heterophoria
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Optic atrophy
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Photophobia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Photopsia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Retinal haemorrhage
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Strabismus
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Abdominal pain
         subjects affected / exposed
    1 / 5 (20.00%)
    5 / 15 (33.33%)
    2 / 12 (16.67%)
    8 / 32 (25.00%)
         occurrences all number
    1
    15
    3
    19
    Abdominal pain upper
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    Anorectal disorder
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Constipation
         subjects affected / exposed
    0 / 5 (0.00%)
    6 / 15 (40.00%)
    1 / 12 (8.33%)
    7 / 32 (21.88%)
         occurrences all number
    0
    8
    1
    9
    Diarrhoea
         subjects affected / exposed
    3 / 5 (60.00%)
    8 / 15 (53.33%)
    2 / 12 (16.67%)
    13 / 32 (40.63%)
         occurrences all number
    3
    12
    2
    17
    Dyschezia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    0
    0
    1
    Eructation
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    2 / 12 (16.67%)
    2 / 32 (6.25%)
         occurrences all number
    0
    0
    3
    3
    Flatulence
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Nausea
         subjects affected / exposed
    1 / 5 (20.00%)
    6 / 15 (40.00%)
    5 / 12 (41.67%)
    12 / 32 (37.50%)
         occurrences all number
    1
    10
    6
    17
    Oral disorder
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    2
    0
    2
    Stomatitis
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    2 / 12 (16.67%)
    4 / 32 (12.50%)
         occurrences all number
    0
    2
    2
    4
    Vomiting
         subjects affected / exposed
    2 / 5 (40.00%)
    12 / 15 (80.00%)
    9 / 12 (75.00%)
    23 / 32 (71.88%)
         occurrences all number
    3
    25
    18
    46
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Dermatitis atopic
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Dermatitis contact
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Dry skin
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Erythema
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    2
    0
    2
    Nail discolouration
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Rash
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 15 (6.67%)
    2 / 12 (16.67%)
    4 / 32 (12.50%)
         occurrences all number
    1
    1
    2
    4
    Rash macular
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Rash maculo-papular
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    3
    0
    3
    Rash morbilliform
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    2
    0
    2
    Urinary retention
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Back pain
         subjects affected / exposed
    1 / 5 (20.00%)
    5 / 15 (33.33%)
    1 / 12 (8.33%)
    7 / 32 (21.88%)
         occurrences all number
    1
    11
    2
    14
    Bone pain
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Bone swelling
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Flank pain
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    2
    0
    2
    Muscle fatigue
         subjects affected / exposed
    2 / 5 (40.00%)
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    2
    0
    0
    2
    Muscle spasms
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Muscular weakness
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    2
    0
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    2 / 12 (16.67%)
    4 / 32 (12.50%)
         occurrences all number
    0
    3
    3
    6
    Musculoskeletal pain
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    1
    1
    0
    2
    Neck pain
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 5 (0.00%)
    5 / 15 (33.33%)
    2 / 12 (16.67%)
    7 / 32 (21.88%)
         occurrences all number
    0
    9
    3
    12
    Pain in jaw
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    2
    2
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 15 (13.33%)
    2 / 12 (16.67%)
    5 / 32 (15.63%)
         occurrences all number
    1
    3
    2
    6
    Device related infection
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Foot and mouth disease
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Myringitis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Oral herpes
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Otitis media
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Rash pustular
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    2 / 12 (16.67%)
    2 / 32 (6.25%)
         occurrences all number
    0
    0
    2
    2
    Skin infection
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    2 / 12 (16.67%)
    4 / 32 (12.50%)
         occurrences all number
    0
    3
    3
    6
    Urinary tract infection
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 5 (20.00%)
    5 / 15 (33.33%)
    2 / 12 (16.67%)
    8 / 32 (25.00%)
         occurrences all number
    1
    5
    3
    9
    Hyperglycaemia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    Hyperkalaemia
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    3 / 32 (9.38%)
         occurrences all number
    1
    1
    1
    3
    Hypermagnesaemia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    1
    1
    Hyperphosphataemia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    1 / 12 (8.33%)
    3 / 32 (9.38%)
         occurrences all number
    0
    4
    1
    5
    Hypocalcaemia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    2
    3
    Hypokalaemia
         subjects affected / exposed
    1 / 5 (20.00%)
    3 / 15 (20.00%)
    0 / 12 (0.00%)
    4 / 32 (12.50%)
         occurrences all number
    1
    3
    0
    4
    Hypomagnesaemia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    1
    2
    Hyponatraemia
         subjects affected / exposed
    1 / 5 (20.00%)
    6 / 15 (40.00%)
    1 / 12 (8.33%)
    8 / 32 (25.00%)
         occurrences all number
    1
    10
    1
    12
    Hypophosphataemia
         subjects affected / exposed
    2 / 5 (40.00%)
    4 / 15 (26.67%)
    0 / 12 (0.00%)
    6 / 32 (18.75%)
         occurrences all number
    2
    8
    0
    10

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jul 2013
    The primary purpose of this amendment was to add additional timepoints to the ECG monitoring to better evaluate and characterize the cardiac repolarization effects of LEE011. In addition, the eligibility criterion was modified to allow the enrollment of patients with tumors other than malignant rhabdoid tumor (MRT) and neuroblastoma who had documented aberrations in the D-cyclin-CDK4/6-INK4a-Rb pathway to the dose escalation part of the study. Information on alternate formulations was added and language around continuous dosing regimen was removed. In addition, updates to some sections, and minor revisions and corrections were made to improve the consistency and clarity of the protocol.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 26 16:26:13 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA