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    Clinical Trial Results:
    A phase I/II open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in subjects with NUT midline carcinoma (NMC) and other cancers

    Summary
    EudraCT number
    2014-004982-25
    Trial protocol
    GB   NL   ES   FR  
    Global end of trial date

    Results information
    Results version number
    v2(current)
    This version publication date
    14 Feb 2020
    First version publication date
    09 May 2019
    Other versions
    v1
    Version creation reason

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    115521
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    27 Nov 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Apr 2018
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    - To determine the safety, tolerability and maximum tolerated dose (MTD) of GSK525762 in subjects 16 years or older following QD and/or BID dosing schedules. - To evaluate the clinical activity of GSK525762 in NMC and other solid tumors. - [US Clinical sites only] To evaluate, after single dose administration, the relative bioavailability of the GSK525762 besylate tablet compared to the amorphous free-base tablet, the effect of high-fat high-calorie meal on the bioavailability of the besylate tablet and the dose proportionality of two doses of GSK525762 administered as the besylate tablets.
    Protection of trial subjects
    Not applicable
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    28 Mar 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
    Australia: 5
    Country: Number of subjects enrolled
    France: 57
    Country: Number of subjects enrolled
    Korea, Republic of: 6
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Spain: 30
    Country: Number of subjects enrolled
    United Kingdom: 13
    Country: Number of subjects enrolled
    United States: 82
    Worldwide total number of subjects
    196
    EEA total number of subjects
    103
    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)
    3
    Adults (18-64 years)
    134
    From 65 to 84 years
    58
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    A total 196 participants were enrolled and randomized in the Part 1 QD (65 participants), Part 1 BID (19 participants), Besylate Substudy (10 participants), and Part 2 (102 participants) groups.

    Pre-assignment
    Screening details
    This was a 2-Part study conducted in 8 countries-Part 1 (dose-escalation) and Part 2 (dose expansion). A besylate sub-study was conducted in 10 participants in the United States.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Part1: GSK525762 2 mg QD
    Arm description
    Participants were administered once daily (QD) oral dose of 2 milligrams (mg) GSK525762
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part1: GSK525762 4 mg QD
    Arm description
    Participants were administered once daily oral dose of 4 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 1: GSK525762 8 mg QD
    Arm description
    Participants were administered once daily oral dose of 8 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 1: GSK525762 16 mg QD
    Arm description
    Participants were administered once daily oral dose of 16 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 1: GSK525762 30 mg QD
    Arm description
    Participants were administered once daily oral dose of 30 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 1: GSK525762 60 mg QD
    Arm description
    Participants were administered once daily oral dose of 60 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 1: GSK525762 80 mg QD
    Arm description
    Participants were administered once daily oral dose of 80 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 1: GSK525762 100 mg QD
    Arm description
    Participants were administered once daily oral dose of 100 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 1: GSK525762 20 mg BID
    Arm description
    Participants were administered twice daily (BID) oral dose of 20 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 twice daily via the oral route with 240 milliliters of water.

    Arm title
    Part 1: GSK525762 30 mg BID
    Arm description
    Participants were administered twice daily oral dose of 30 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 twice daily via the oral route with 240 milliliters of water.

    Arm title
    Part 1: GSK525762 40 mg BID
    Arm description
    Participants were administered twice daily oral dose of 40 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 twice daily via the oral route with 240 milliliters of water.

    Arm title
    Part 2: Participants with NMC
    Arm description
    Participants with NUT Midline Carcinoma (NMC) were administered continuous once daily oral dose of 75 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 2: Participants with SCLC
    Arm description
    Participants with small cell lung cancer(SCLC) were administered continuous once daily oral dose of 75 mg GSK525762
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 2: Participants with CRPC
    Arm description
    Participants with Castrate-Resistant Prostate Cancer (CRPR) were administered continuous once daily oral dose of 75 mg GSK525762
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 2: Participants with TNBC
    Arm description
    Participants with Triple Negative Breast Cancer (TNBC) were administered continuous once daily oral dose of 75 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 2: Participants with ER+BC
    Arm description
    Participants with estrogen receptor positive breast cancer (ER+BC) were administered continuous once daily oral dose of 75 mg GSK525762
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    Part 2: Participants with GIST
    Arm description
    Participants with Gastrointestinal Stromal Tumor (GIST) were administered continuous once daily oral dose of 75 mg GSK525762.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Arm description
    Participants received GSK525762 80 mg amorphous (amor) freebase tablet along with 6 mg stable isotope (iso) in solution in the fasted state in Period 1 followed by administration of GSK525762 80 mg besylate (bes) tablet along with 6 mg stable iso in solution in the fasted state in Period 2. Participants were then administered GSK525762 30 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 3 and GSK525762 80 mg bes tablet was administered with Food and Drug Administration (FDA) recommended high fat breakfast in Period 4.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Arm title
    80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Arm description
    Participants received GSK525762 80 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 1 followed by administration GSK525762 80 mg amor free-base tablet along with 6 mg stable iso in solution in the fasted state in Period 2. Participants were then administered 30 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 3 and GSK525762 80 mg bes tablet was administered with FDA recommended high fat breakfast in Period 4.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK525762
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GSK525762 was available as white to slightly coloured, round, biconvex, film coated tablets. Participants were administered GSK525762 once daily via the oral route with 240 milliliters of water.

    Number of subjects in period 1
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID Part 2: Participants with NMC Part 2: Participants with SCLC Part 2: Participants with CRPC Part 2: Participants with TNBC Part 2: Participants with ER+BC Part 2: Participants with GIST 80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Started
    3
    4
    1
    3
    4
    9
    32
    9
    4
    10
    5
    12
    14
    23
    19
    21
    13
    5
    5
    Completed
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Not completed
    3
    4
    1
    3
    4
    8
    32
    9
    3
    10
    5
    12
    14
    22
    19
    21
    13
    5
    5
         Physician decision
    1
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
    -
    -
    -
    -
    -
    -
    -
         Site closed
    -
    -
    -
    -
    -
    -
    2
    -
    -
    1
    1
    2
    2
    1
    1
    3
    8
    -
    -
         Adverse event, serious fatal
    2
    4
    1
    3
    4
    7
    30
    7
    1
    9
    3
    8
    12
    21
    16
    17
    5
    5
    4
         Consent withdrawn by subject
    -
    -
    -
    -
    -
    -
    -
    -
    1
    -
    1
    -
    -
    -
    -
    1
    -
    -
    1
         Lost to follow-up
    -
    -
    -
    -
    -
    1
    -
    2
    1
    -
    -
    1
    -
    -
    2
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part1: GSK525762 2 mg QD
    Reporting group description
    Participants were administered once daily (QD) oral dose of 2 milligrams (mg) GSK525762

    Reporting group title
    Part1: GSK525762 4 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 4 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 8 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 8 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 16 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 16 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 30 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 30 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 60 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 60 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 80 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 80 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 100 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 100 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 20 mg BID
    Reporting group description
    Participants were administered twice daily (BID) oral dose of 20 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 30 mg BID
    Reporting group description
    Participants were administered twice daily oral dose of 30 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 40 mg BID
    Reporting group description
    Participants were administered twice daily oral dose of 40 mg GSK525762.

    Reporting group title
    Part 2: Participants with NMC
    Reporting group description
    Participants with NUT Midline Carcinoma (NMC) were administered continuous once daily oral dose of 75 mg GSK525762.

    Reporting group title
    Part 2: Participants with SCLC
    Reporting group description
    Participants with small cell lung cancer(SCLC) were administered continuous once daily oral dose of 75 mg GSK525762

    Reporting group title
    Part 2: Participants with CRPC
    Reporting group description
    Participants with Castrate-Resistant Prostate Cancer (CRPR) were administered continuous once daily oral dose of 75 mg GSK525762

    Reporting group title
    Part 2: Participants with TNBC
    Reporting group description
    Participants with Triple Negative Breast Cancer (TNBC) were administered continuous once daily oral dose of 75 mg GSK525762.

    Reporting group title
    Part 2: Participants with ER+BC
    Reporting group description
    Participants with estrogen receptor positive breast cancer (ER+BC) were administered continuous once daily oral dose of 75 mg GSK525762

    Reporting group title
    Part 2: Participants with GIST
    Reporting group description
    Participants with Gastrointestinal Stromal Tumor (GIST) were administered continuous once daily oral dose of 75 mg GSK525762.

    Reporting group title
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Reporting group description
    Participants received GSK525762 80 mg amorphous (amor) freebase tablet along with 6 mg stable isotope (iso) in solution in the fasted state in Period 1 followed by administration of GSK525762 80 mg besylate (bes) tablet along with 6 mg stable iso in solution in the fasted state in Period 2. Participants were then administered GSK525762 30 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 3 and GSK525762 80 mg bes tablet was administered with Food and Drug Administration (FDA) recommended high fat breakfast in Period 4.

    Reporting group title
    80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Reporting group description
    Participants received GSK525762 80 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 1 followed by administration GSK525762 80 mg amor free-base tablet along with 6 mg stable iso in solution in the fasted state in Period 2. Participants were then administered 30 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 3 and GSK525762 80 mg bes tablet was administered with FDA recommended high fat breakfast in Period 4.

    Reporting group values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID Part 2: Participants with NMC Part 2: Participants with SCLC Part 2: Participants with CRPC Part 2: Participants with TNBC Part 2: Participants with ER+BC Part 2: Participants with GIST 80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes Total
    Number of subjects
    3 4 1 3 4 9 32 9 4 10 5 12 14 23 19 21 13 5 5 196
    Age categorical
    Units: Subjects
        All study participants
    3 4 1 3 4 9 32 9 4 10 5 12 14 23 19 21 13 5 5 196
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    40.0 ± 15.77 47.0 ± 19.44 39.0 ± 99999 53.7 ± 4.19 49.3 ± 23.27 46.7 ± 17.06 51.5 ± 16.82 58.3 ± 19.92 66.5 ± 6.45 63.5 ± 8.42 60.4 ± 4.83 42.9 ± 18.05 58.3 ± 11.04 63.8 ± 6.11 50.8 ± 8.66 59.7 ± 10.34 61.0 ± 13.23 56.8 ± 12.02 53.6 ± 5.39 -
    Sex: Female, Male
    Units: Subjects
        Female
    1 3 1 3 1 6 14 2 2 4 1 7 9 0 19 21 6 3 2 105
        Male
    2 1 0 0 3 3 18 7 2 6 4 5 5 23 0 0 7 2 3 91
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1
        Central/South Asian Heritage (Her)
    1 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 3
        Japanese Her/East Asian Her/South East Asian Her
    0 1 0 0 0 0 0 0 1 0 0 2 3 0 1 0 1 0 0 9
        Black or African American
    0 0 0 1 0 1 2 1 0 0 0 0 2 0 2 1 1 1 0 12
        White
    2 3 0 2 4 7 30 8 3 10 5 6 8 23 15 18 10 4 5 163
        Missing
    0 0 0 0 0 0 0 0 0 0 0 3 1 0 1 2 1 0 0 8

    End points

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    End points reporting groups
    Reporting group title
    Part1: GSK525762 2 mg QD
    Reporting group description
    Participants were administered once daily (QD) oral dose of 2 milligrams (mg) GSK525762

    Reporting group title
    Part1: GSK525762 4 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 4 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 8 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 8 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 16 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 16 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 30 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 30 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 60 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 60 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 80 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 80 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 100 mg QD
    Reporting group description
    Participants were administered once daily oral dose of 100 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 20 mg BID
    Reporting group description
    Participants were administered twice daily (BID) oral dose of 20 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 30 mg BID
    Reporting group description
    Participants were administered twice daily oral dose of 30 mg GSK525762.

    Reporting group title
    Part 1: GSK525762 40 mg BID
    Reporting group description
    Participants were administered twice daily oral dose of 40 mg GSK525762.

    Reporting group title
    Part 2: Participants with NMC
    Reporting group description
    Participants with NUT Midline Carcinoma (NMC) were administered continuous once daily oral dose of 75 mg GSK525762.

    Reporting group title
    Part 2: Participants with SCLC
    Reporting group description
    Participants with small cell lung cancer(SCLC) were administered continuous once daily oral dose of 75 mg GSK525762

    Reporting group title
    Part 2: Participants with CRPC
    Reporting group description
    Participants with Castrate-Resistant Prostate Cancer (CRPR) were administered continuous once daily oral dose of 75 mg GSK525762

    Reporting group title
    Part 2: Participants with TNBC
    Reporting group description
    Participants with Triple Negative Breast Cancer (TNBC) were administered continuous once daily oral dose of 75 mg GSK525762.

    Reporting group title
    Part 2: Participants with ER+BC
    Reporting group description
    Participants with estrogen receptor positive breast cancer (ER+BC) were administered continuous once daily oral dose of 75 mg GSK525762

    Reporting group title
    Part 2: Participants with GIST
    Reporting group description
    Participants with Gastrointestinal Stromal Tumor (GIST) were administered continuous once daily oral dose of 75 mg GSK525762.

    Reporting group title
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Reporting group description
    Participants received GSK525762 80 mg amorphous (amor) freebase tablet along with 6 mg stable isotope (iso) in solution in the fasted state in Period 1 followed by administration of GSK525762 80 mg besylate (bes) tablet along with 6 mg stable iso in solution in the fasted state in Period 2. Participants were then administered GSK525762 30 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 3 and GSK525762 80 mg bes tablet was administered with Food and Drug Administration (FDA) recommended high fat breakfast in Period 4.

    Reporting group title
    80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Reporting group description
    Participants received GSK525762 80 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 1 followed by administration GSK525762 80 mg amor free-base tablet along with 6 mg stable iso in solution in the fasted state in Period 2. Participants were then administered 30 mg bes tablet along with 6 mg stable iso in solution in the fasted state in Period 3 and GSK525762 80 mg bes tablet was administered with FDA recommended high fat breakfast in Period 4.

    Subject analysis set title
    Participants with NMC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with NUT Midline Carcinoma (NMC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with SCLC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with small cell lung cancer(SCLC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with CRPC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with Castrate-Resistant Prostate Cancer (CRPC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with TNBC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with Triple Negative Breast Cancer (TNBC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with ER+BC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with estrogen receptor positive breast cancer (ER+BC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with GIST
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with Gastrointestinal Stromal Tumor (GIST) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    All participants in Besylate sub-study
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All participants who entered besylate sub-study and received 80 mg amor free-base tablet along with 6 mg stable iso in solution in fasted state; 80 mg bes tablet along with 6 mg stable iso in solution in fasted state, 30 mg bes tablet along with 6 mg stable iso in solution in fasted state and 80 mg bes tablet with FDA recommended high fat breakfast in one of the treatment periods were included.

    Subject analysis set title
    Participants with NMC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with NUT Midline Carcinoma (NMC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with CRPC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with Castrate-Resistant Prostate Cancer (CRPC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with ER+BC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with estrogen receptor positive breast cancer (ER+BC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with GIST
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with Gastrointestinal Stromal Tumor (GIST) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with ER+BC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with estrogen receptor positive breast cancer (ER+BC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    GSK525762 80 mg amorphous+6 mg stable isotope
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants were administered GSK525762 80 mg amorphous free-base tablet along with 6 mg stable isotope in the fasted state.

    Subject analysis set title
    GSK525762 80 mg besylate+6 mg stable isotope
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants were administered GSK525762 80 mg besylate tablet along with 6 mg stable isotope in solution in fasted state.

    Subject analysis set title
    GSK525762 30 mg besylate+6 mg stable isotope
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants were administered GSK525762 30 mg besylate tablet along with 6 mg stable isotope in solution in fasted state.

    Subject analysis set title
    GSK525762 80 mg besylate fed
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants were administered GSK525762 80 mg besylate tablet along with Food and Drug Administration (FDA) recommended high fat breakfast.

    Subject analysis set title
    Participants with NMC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with NUT Midline Carcinoma (NMC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with SCLC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with small cell lung cancer(SCLC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with CRPC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with Castrate-Resistant Prostate Cancer (CRPC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with TNBC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with Triple Negative Breast Cancer (TNBC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with ER+BC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with estrogen receptor positive breast cancer (ER+BC) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Participants with GIST
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with Gastrointestinal Stromal Tumor (GIST) were administered continuous once daily oral dose of 75 mg GSK525762

    Subject analysis set title
    Part 1: GSK525762 2 mg QD
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants were administered once daily oral dose of 2 mg GSK525762.

    Subject analysis set title
    Part 1: GSK525762 4 mg QD
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants were administered once daily oral dose of 4 mg GSK525762.

    Subject analysis set title
    Part 1: GSK525762 8 mg QD
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants were administered once daily oral dose of 8 mg GSK525762.

    Subject analysis set title
    Part 1: GSK525762 16 mg QD
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants were administered once daily oral dose of 16 mg GSK525762.

    Subject analysis set title
    Part 1: GSK525762 30 mg QD
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants were administered once daily oral dose of 30 mg GSK525762.

    Primary: Number of participants with adverse events (AEs) and serious adverse events (SAEs)-Part 1 QD

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    End point title
    Number of participants with adverse events (AEs) and serious adverse events (SAEs)-Part 1 QD [1] [2]
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the outcomes mentioned; events of possible study treatment-induced liver injury with hyperbilirubinemia; any new primary cancers; significant cardiac dysfunction; Grade 4 laboratory abnormalities; and drug related hepatobiliary event leading to permanent discontinuation of study treatment.
    End point type
    Primary
    End point timeframe
    Median of 1.38 months of drug exposure
    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 statistical analysis was performed
    [2] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [3]
    4 [4]
    1 [5]
    3 [6]
    4 [7]
    9 [8]
    32 [9]
    9 [10]
    Units: Participants
        Any AE
    3
    4
    1
    3
    3
    9
    31
    9
        Any SAE
    0
    2
    0
    0
    1
    2
    21
    3
    Notes
    [3] - All Treated Population
    [4] - All Treated Population
    [5] - All Treated Population
    [6] - All Treated Population
    [7] - All Treated Population-participants who received at least one dose of study treatment
    [8] - All Treated Population
    [9] - All Treated Population
    [10] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with AEs and SAEs-Part 1 BID

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    End point title
    Number of participants with AEs and SAEs-Part 1 BID [11] [12]
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the outcomes mentioned; events of possible study treatment-induced liver injury with hyperbilirubinemia; any new primary cancers; significant cardiac dysfunction; Grade 4 laboratory abnormalities; and drug related hepatobiliary event leading to permanent discontinuation of study treatment
    End point type
    Primary
    End point timeframe
    Median of 1.41 months of drug exposure
    Notes
    [11] - 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 statistical analysis was performed
    [12] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [13]
    10 [14]
    5 [15]
    Units: Participants
        Any AE
    4
    10
    5
        Any SAE
    0
    4
    2
    Notes
    [13] - All Treated Population
    [14] - All Treated Population
    [15] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with AEs and SAEs-Part 2

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    End point title
    Number of participants with AEs and SAEs-Part 2 [16]
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the outcomes mentioned; events of possible study treatment-induced liver injury with hyperbilirubinemia; any new primary cancers; significant cardiac dysfunction; Grade 4 laboratory abnormalities; and drug related hepatobiliary event leading to permanent discontinuation of study treatment.
    End point type
    Primary
    End point timeframe
    Median of 1.41 months of drug exposure
    Notes
    [16] - 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 statistical analysis was performed
    End point values
    Participants with NMC Participants with SCLC Participants with CRPC Participants with TNBC Participants with ER+BC Participants with GIST
    Number of subjects analysed
    12 [17]
    14 [18]
    23 [19]
    19 [20]
    21 [21]
    13 [22]
    Units: Participants
        Any AE
    11
    14
    23
    19
    21
    13
        Any SAE
    6
    9
    16
    11
    15
    8
    Notes
    [17] - All Treated Population
    [18] - All Treated Population
    [19] - All Treated Population
    [20] - All Treated Population
    [21] - All Treated Population
    [22] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with non-serious AEs and SAEs-Besylate sub-study

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    End point title
    Number of participants with non-serious AEs and SAEs-Besylate sub-study [23] [24]
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the outcomes mentioned; events of possible study treatment-induced liver injury with hyperbilirubinemia; any new primary cancers; significant cardiac dysfunction; Grade 4 laboratory abnormalities; and drug related hepatobiliary event leading to permanent discontinuation of study treatment.
    End point type
    Primary
    End point timeframe
    Median of 1.87 months of drug exposure
    Notes
    [23] - 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 statistical analysis was performed
    [24] - 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: The end point is specific for Part 1 QD dosing
    End point values
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Number of subjects analysed
    5 [25]
    5 [26]
    Units: Participants
        Any non-serious AE
    5
    5
        Any SAE
    3
    3
    Notes
    [25] - All Treated Population
    [26] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with dose reductions or delays-Part 1 QD

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    End point title
    Number of participants with dose reductions or delays-Part 1 QD [27] [28]
    End point description
    The number of participants who had any dose reductions or delays is presented.
    End point type
    Primary
    End point timeframe
    Median of 1.38 months of drug exposure
    Notes
    [27] - 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 statistical analysis was performed
    [28] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [29]
    4 [30]
    1 [31]
    3 [32]
    4 [33]
    9 [34]
    32 [35]
    9 [36]
    Units: Participants
    0
    0
    0
    0
    0
    2
    8
    7
    Notes
    [29] - All Treated Population
    [30] - All Treated Population
    [31] - All Treated Population
    [32] - All Treated Population
    [33] - All Treated Population
    [34] - All Treated Population
    [35] - All Treated Population
    [36] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with dose reductions or delays-Part 1 BID

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    End point title
    Number of participants with dose reductions or delays-Part 1 BID [37] [38]
    End point description
    The number of participants who had any dose reductions or delays is presented.
    End point type
    Primary
    End point timeframe
    Median of 1.41 months of drug exposure
    Notes
    [37] - 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 statistical analysis was performed
    [38] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [39]
    10 [40]
    5 [41]
    Units: Participants
    0
    3
    1
    Notes
    [39] - All Treated Population
    [40] - All Treated Population
    [41] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with dose reductions or delays-Part 2

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    End point title
    Number of participants with dose reductions or delays-Part 2 [42]
    End point description
    The number of participants who had any dose reductions or delays is presented.
    End point type
    Primary
    End point timeframe
    Median of 1.41 months of drug exposure
    Notes
    [42] - 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 statistical analysis was performed
    End point values
    Participants with NMC Participants with SCLC Participants with CRPC Participants with TNBC Participants with ER+BC Participants with GIST
    Number of subjects analysed
    12 [43]
    14 [44]
    23 [45]
    19 [46]
    21 [47]
    13 [48]
    Units: Participants
    7
    4
    11
    6
    6
    4
    Notes
    [43] - All Treated Population
    [44] - All Treated Population
    [45] - All Treated Population
    [46] - All Treated Population
    [47] - All Treated Population
    [48] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with dose reductions or delays-Besylate sub-study

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    End point title
    Number of participants with dose reductions or delays-Besylate sub-study [49] [50]
    End point description
    The number of participants who had any dose reductions or delays is presented.
    End point type
    Primary
    End point timeframe
    Median of 1.87 months of drug exposure
    Notes
    [49] - 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 statistical analysis was performed
    [50] - 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: The end point is specific for Part 1 QD dosing
    End point values
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Number of subjects analysed
    5 [51]
    5 [52]
    Units: Participants
    3
    1
    Notes
    [51] - All Treated Population
    [52] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants withdrawn due to toxicities-Part 1 QD

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    End point title
    Number of participants withdrawn due to toxicities-Part 1 QD [53] [54]
    End point description
    Number of participants withdrawn due to toxicities is presented.
    End point type
    Primary
    End point timeframe
    Median of 1.38 months of drug exposure
    Notes
    [53] - 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 statistical analysis was performed
    [54] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [55]
    4 [56]
    1 [57]
    3 [58]
    4 [59]
    9 [60]
    32 [61]
    9 [62]
    Units: Participants
    0
    1
    0
    0
    0
    2
    7
    2
    Notes
    [55] - All Treated Population
    [56] - All Treated Population
    [57] - All Treated Population
    [58] - All Treated Population
    [59] - All Treated Population
    [60] - All Treated Population
    [61] - All Treated Population
    [62] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants withdrawn due to toxicities-Part 1 BID

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    End point title
    Number of participants withdrawn due to toxicities-Part 1 BID [63] [64]
    End point description
    Number of participants withdrawn due to toxicities is presented.
    End point type
    Primary
    End point timeframe
    Median of 1.41 months of drug exposure
    Notes
    [63] - 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 statistical analysis was performed
    [64] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [65]
    10 [66]
    5 [67]
    Units: Participants
    0
    2
    2
    Notes
    [65] - All Treated Population
    [66] - All Treated Population
    [67] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants withdrawn due to toxicities-Part 2

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    End point title
    Number of participants withdrawn due to toxicities-Part 2 [68]
    End point description
    Number of participants withdrawn due to toxicities is presented.
    End point type
    Primary
    End point timeframe
    Median of 1.41 months of drug exposure
    Notes
    [68] - 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 statistical analysis was performed
    End point values
    Participants with NMC Participants with SCLC Participants with CRPC Participants with TNBC Participants with ER+BC Participants with GIST
    Number of subjects analysed
    12 [69]
    14 [70]
    23 [71]
    19 [72]
    21 [73]
    13 [74]
    Units: Participants
    1
    3
    6
    4
    6
    2
    Notes
    [69] - All Treated Population
    [70] - All Treated Population
    [71] - All Treated Population
    [72] - All Treated Population
    [73] - All Treated Population
    [74] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants withdrawn due to toxicities-Besylate sub-study

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    End point title
    Number of participants withdrawn due to toxicities-Besylate sub-study [75] [76]
    End point description
    Number of participants withdrawn due to toxicities is presented.
    End point type
    Primary
    End point timeframe
    Median of 1.87 months of drug exposure
    Notes
    [75] - 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 statistical analysis was performed
    [76] - 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: The end point is specific for Part 1 QD dosing
    End point values
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Number of subjects analysed
    5 [77]
    5 [78]
    Units: Participants
    0
    0
    Notes
    [77] - All Treated Population
    [78] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with grade change from Baseline in clinical chemistry data-Part 1 QD

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    End point title
    Number of participants with grade change from Baseline in clinical chemistry data-Part 1 QD [79] [80]
    End point description
    Blood samples were collected for analysis of: glucose, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), direct bilirubin (Dir bil), bilirubin, N-Terminal proB-type natriuretic peptide (NT-BNP), calcium, cholesterol, creatine kinase (CK), chloride, carbon dioxide (CO2), creatinine, gamma glutamyl transferase (GGT), high and low density lipoprotein (HDL and LDL), insulin, potassium, lactate dehydrogenase (LDH), lipase, magnesium, protein, sodium, thyroxine, testosterone, triglycerides, troponin I and T, urate and urea. Grading using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Data for worst case post-Baseline is presented. Only participants with data available at specified time points were analyzed (indicated by n=X in category titles). 99999 indicates data not available due to insufficient participants.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.38 months of drug exposure
    Notes
    [79] - 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 statistical analysis was performed
    [80] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [81]
    4 [82]
    1 [83]
    3 [84]
    4 [85]
    9 [86]
    32 [87]
    9 [88]
    Units: Participants
        Glucose; Any grade increase; n=4,9,32,9,2,4,1,3
    0
    2
    1
    3
    2
    7
    24
    8
        Glucose; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    2
    3
        Glucose; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Albumin; Any grade increase; n=4,9,32,9,2,4,1,3
    0
    2
    0
    0
    1
    3
    12
    1
        Albumin; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Albumin; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        ALP; Any grade increase; n=4,9,31,9,2,4,1,3
    0
    0
    0
    0
    1
    0
    7
    0
        ALP; Increase to Grade 3; n=4,9,31,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    1
    0
        ALP;Increase to Grade 4; n=4,9,31,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        ALT; Any grade increase; n=4,9,32,9,2,4,1,3
    0
    1
    0
    0
    1
    1
    9
    2
        ALT; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        ALT; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Amylase; Any grade increase; n=4,9,32,9,2,4,1,3
    1
    1
    0
    1
    2
    0
    10
    1
        Amylase; Increase to Grade3;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    1
    1
        Amylase;Increase to Grade4;n=4,9,32,9,2,4,1,3
    0
    1
    0
    0
    0
    0
    1
    0
        AST;Any grade increase; n=4,9,32,92,4,1,3
    2
    1
    1
    0
    2
    1
    14
    3
        AST; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    1
        AST; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Dir bil; Any grade increase;n=4,9,30,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Dir bil; Increase to Grade 3;n=4,9,30,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Dir bil; Increase to Grade 4;n=4,9,30,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Bilirubin; Any grade increase;n=4,9,30,9,2,4,1,3
    0
    0
    1
    0
    1
    1
    15
    8
        Bilirubin; Increase to Grade3;n=4,9,30,9,2,4,1,3
    0
    0
    0
    0
    1
    0
    5
    1
        Bilirubin; Increase to Grade4;n=4,9,30,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        NT-BNP; Any grade increase;n=4,9,30,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        NT-BNP; Increase to Grade 3;n=4,9,30,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        NT-BNP; Increase to Grade 4;n=4, 9, 30, 9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Calcium; Any grade increase;n=4,9,32, 9,2,4,1,3
    1
    1
    0
    1
    2
    1
    17
    3
        Calcium; Increase to Grade3;n=4,9,32,9,2,4,1,3
    1
    0
    0
    0
    0
    0
    0
    0
        Calcium; Increase to Grade 4;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Cholesterol;Any grade increase;n=4,7,29,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    11
    1
        Cholesterol;Increase to Grade3;n=4,7,29,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Cholesterol;Increase to Grade4;n=4,7,29,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        CK; Any grade increase; n=4,9,31,9,3,4,1,3
    0
    1
    0
    0
    1
    0
    11
    5
        CK; Increase to Grade 3; n=4,9,31,9,3,4,1,3
    0
    0
    0
    0
    0
    0
    2
    0
        CK; Increase to Grade 4;n=4,9,31,9,3,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Chloride; Any grade increase; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Chloride; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Chloride; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        CO2; Any grade increase;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        CO2; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        CO2; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Creatinine;Any grade increase;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    1
    0
    7
    3
        Creatinine;Increase to Grade 3;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    1
    0
        Creatinine;Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        GGT; Any grade increase; n=4,9,31,7,2,4,1,3
    0
    1
    0
    0
    1
    0
    11
    1
        GGT; Increase to Grade 3;n=4,9,31,7,2,4,1,3
    0
    0
    0
    0
    0
    0
    2
    0
        GGT; Increase to Grade 4; n=4,9,31,7,2,4,1,3
    0
    0
    0
    0
    0
    0
    1
    0
        HDL; Any grade increase; n=4,7,28,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        HDL; Increase to Grade 3;n=4,7,28,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        HDL; Increase to Grade 4; n=4,7,28,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Insulin; Any grade increase; n=4,9,31,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Insulin; Increase to Grade 3; n=4,9,31,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Insulin; Increase to Grade 4; n=4,9,31,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Potassium; Any grade increase; n=4,9,32,9,3,4,1,3
    2
    2
    0
    3
    0
    2
    13
    3
        Potassium; Increase to Grade 3; n=4,9,32,9,3,4,1,3
    0
    0
    0
    0
    0
    0
    1
    1
        Potassium; Increase to Grade 4; n=4,9,32,9,3,4,1,3
    0
    0
    0
    0
    0
    0
    1
    0
        LDH; Any grade increase;n=0, 1, 0, 0,0,0,0,0
    99999
    99999
    99999
    99999
    99999
    0
    99999
    99999
        LDH; Increase to Grade 3;n=0, 1, 0, 0,0,0,0,0
    99999
    99999
    99999
    99999
    99999
    0
    99999
    99999
        LDH; Increase to Grade 4;n=0, 1, 0, 0,0,0,0,0
    99999
    99999
    99999
    99999
    99999
    0
    99999
    99999
        LDL; Any grade increase; n=4, 7, 28,8,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        LDL; Increase to Grade 3;n=4, 7, 28,8,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        LDL; Increase to Grade 4; n=4, 7, 28,8,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Lipase; Any grade increase; n=4,9,31,9,2,4,1,3
    1
    0
    0
    0
    0
    0
    8
    2
        Lipase; Increase to Grade 3; n=4,9,31,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    3
    0
        Lipase; Increase to Grade 4; n=4,9,31,9,2,4,1,3
    1
    0
    0
    0
    0
    0
    0
    0
        Magnesium; Any grade increase; n=4,9,32,9,3,4,1,3
    0
    2
    1
    1
    1
    0
    9
    2
        Magnesium; Increase to Grade 3; n=4,9,32,9,3,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Magnesium; Increase to Grade 4;n=4,9,32,9,3,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Protein; Any grade increase; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Protein; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Protein; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Sodium; Any grade increase; n=4,9,32,9,3,4,1,3
    1
    3
    0
    1
    2
    3
    16
    4
        Sodium; Increase to Grade 3; n=4,9,32,9,3,4,1,3
    0
    0
    0
    0
    1
    0
    4
    0
        Sodium; Increase to Grade 4; n=4,9,32,9,3,4,1,3
    0
    1
    0
    0
    0
    0
    0
    0
        Thyroxine; Any grade increase; n=4,7,29,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Thyroxine; Increase to Grade 3; n=4,7,29,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Thyroxine; Increase to Grade 4; n=4,7,29,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Testosterone;Any grade increase;n=3,3,14,7,1,0,0,0
    0
    99999
    99999
    99999
    0
    0
    0
    0
        Testosterone;Increase to Grade3;n=3,3,14,7,1,0,0,0
    0
    99999
    99999
    99999
    0
    0
    0
    0
        Testosterone;Increase to Grade4;n=3,3,14,7,1,0,0,0
    0
    99999
    99999
    99999
    0
    0
    0
    0
        Triglyc; Any grade increase;n=4,7,29,9,2,4,1,3
    0
    2
    0
    0
    2
    2
    17
    6
        Triglyc; Increase to Grade 3; n=4,7,29,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Triglyc; Increase to Grade 4; n=4,7,29,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    1
        Troponin I; Any grade increase;n=2,5,24,5,0,0,0,0
    99999
    99999
    99999
    99999
    0
    0
    0
    0
        Troponin I; Increase to Grade3;n=2,5,24,5,0,0,0,0
    99999
    99999
    99999
    99999
    0
    0
    0
    0
        Troponin I;Increase to Grade4;n=2,5,24,5,0,0,0,0
    99999
    99999
    99999
    99999
    0
    0
    0
    0
        Troponin T;Any grade increase;n=4,9,31,9,3,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Troponin T; Increase to Grade3;n=4,9,31,9,3,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Troponin T;Increase to Grade4;n=4,9,31,9,3,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Urate;Any grade increase;n=4,9,32,9,2,4,1,3
    1
    0
    0
    0
    1
    0
    1
    0
        Urate;Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Urate;Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    1
    0
    1
    0
        Urea;Any grade increase; n=4,9,31,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Urea;Increase to Grade 3; n=4,9,31,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Urea;Increase to Grade 4; n=4,9,31,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
    Notes
    [81] - All Treated Population
    [82] - All Treated Population
    [83] - All Treated Population
    [84] - All Treated Population
    [85] - All Treated Population
    [86] - All Treated Population
    [87] - All Treated Population
    [88] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with grade change from Baseline in clinical chemistry data-Part 1 BID

    Close Top of page
    End point title
    Number of participants with grade change from Baseline in clinical chemistry data-Part 1 BID [89] [90]
    End point description
    Blood samples were collected for the analysis of clinical chemistry parameters: glucose, albumin, ALP, ALT, amylase, AST, Dir bil, bilirubin, NT-BNP, calcium, cholesterol, CK, chloride, CO2, creatinine, GGT, HDL and LDL cholesterol, insulin, potassium, LDH, lipase, magnesium, protein, sodium, thyroxine, testosterone, triglycerides, troponin I and T, urate and urea. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life–threatening consequences; Grade 5: death. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post-Baseline is presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.41 months of drug exposure
    Notes
    [89] - 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 statistical analysis was performed
    [90] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [91]
    10 [92]
    5 [93]
    Units: Participants
        Glucose; Any grade increase; n=4, 10, 5
    1
    9
    5
        Glucose; Increase to Grade 3; n=4, 10, 5
    1
    3
    1
        Glucose; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Albumin; Any grade increase; n=4, 10, 5
    0
    4
    1
        Albumin; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Albumin; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        ALP; Any grade increase; n=4, 10, 5
    0
    4
    2
        ALP; Increase to Grade 3; n=4, 10, 5
    0
    2
    0
        ALP; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        ALT; Any grade increase; n=4, 10, 5
    0
    5
    1
        ALT; Increase to Grade 3; n=4, 10, 5
    0
    1
    0
        ALT; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Amylase; Any grade increase; n=4, 10, 5
    0
    2
    2
        Amylase; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Amylase; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        AST; Any grade increase; n=4, 10, 5
    2
    6
    1
        AST; Increase to Grade 3; n=4, 10, 5
    0
    2
    0
        AST; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Dir bil; Any grade increase; n=4, 9, 4
    0
    0
    0
        Dir bil; Increase to Grade 3; n=4, 9, 4
    0
    0
    0
        Dir bil; Increase to Grade 4; n=4, 9, 4
    0
    0
    0
        Bilirubin; Any grade increase; n=4, 10, 5
    1
    7
    2
        Bilirubin; Increase to Grade 3; n=4, 10, 5
    1
    1
    1
        Bilirubin; Increase to Grade 4; n=4, 10, 5
    0
    1
    0
        NT-BNP; Any grade increase; n=4, 10, 5
    0
    0
    0
        NT-BNP; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        NT-BNP; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Calcium; Any grade increase; n=4, 10, 5
    1
    2
    1
        Calcium; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Calcium; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Cholesterol; Any grade increase; n=2, 9, 5
    0
    2
    0
        Cholesterol; Increase to Grade 3; n=2, 9, 5
    0
    0
    0
        Cholesterol; Increase to Grade 4; n=2, 9, 5
    0
    0
    0
        CK; Any grade increase; n=4, 10, 5
    0
    3
    2
        CK; Increase to Grade 3; n=n=4, 10, 5
    0
    0
    0
        CK; Increase to Grade 4; n=n=4, 10, 5
    0
    0
    0
        Chloride; Any grade increase; n=4, 10, 5
    0
    0
    0
        Chloride; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Chloride; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        CO2; Any grade increase; n=4, 10, 5
    0
    0
    0
        CO2; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        CO2; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Creatinine; Any grade increase; n=4, 10, 5
    0
    2
    2
        Creatinine; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Creatinine; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        GGT; Any grade increase; n=4, 10, 5
    0
    4
    1
        GGT; Increase to Grade 3; n=4, 10, 5
    0
    1
    0
        GGT; Increase to Grade 4; n=4, 10, 5
    0
    1
    0
        HDL; Any grade increase; n=2, 9, 5
    0
    0
    0
        HDL; Increase to Grade 3; n=2, 9, 5
    0
    0
    0
        HDL; Increase to Grade 4; n=2, 9, 5
    0
    0
    0
        Insulin; Any grade increase; n=4, 10, 5
    0
    0
    0
        Insulin; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Insulin; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Potassium; Any grade increase; n=4, 10, 5
    1
    5
    2
        Potassium; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Potassium; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        LDL; Any grade increase; n=2, 9, 5
    0
    0
    0
        LDL; Increase to Grade 3; n=2, 9, 5
    0
    0
    0
        LDL; Increase to Grade 4; n=2, 9, 5
    0
    0
    0
        Lipase; Any grade increase; n=4, 10, 5
    0
    2
    3
        Lipase; Increase to Grade 3; n=4, 10, 5
    0
    1
    0
        Lipase; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Magnesium; Any grade increase; n=4, 10, 5
    0
    2
    2
        Magnesium; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Magnesium; Increase to Grade 4; n=4, 10, 5
    0
    1
    0
        Protein; Any grade increase; n=4, 10, 5
    0
    0
    0
        Protein; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Protein; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Sodium; Any grade increase; n=4, 10, 5
    0
    7
    2
        Sodium; Increase to Grade 3; n=4, 10, 5
    0
    2
    0
        Sodium; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Thyroxine; Any grade increase; n=3, 9, 5
    0
    0
    0
        Thyroxine; Increase to Grade 3; n=3, 9, 5
    0
    0
    0
        Thyroxine; Increase to Grade 4; n=3, 9, 5
    0
    0
    0
        Testosterone; Any grade increase; n=1, 4, 4
    0
    0
    0
        Testosterone; Increase to Grade 3; n=1, 4, 4
    0
    0
    0
        Testosterone; Increase to Grade 4; n=1, 4, 4
    0
    0
    0
        Triglycerides; Any grade increase; n=2, 9, 5
    0
    4
    4
        Triglycerides; Increase to Grade 3; n=2, 9, 5
    0
    0
    0
        Triglycerides; Increase to Grade 4; n=2, 9, 5
    0
    0
    0
        Troponin I; Any grade increase; n=3, 10, 5
    0
    0
    0
        Troponin I; Increase to Grade 3; n=3, 10, 5
    0
    0
    0
        Troponin I; Increase to Grade 4; n=3, 10, 5
    0
    0
    0
        Troponin T; Any grade increase; n=4, 10, 5
    0
    0
    0
        Troponin T; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Troponin T; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Urate; Any grade increase; n=4, 10, 5
    0
    0
    0
        Urate; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Urate; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
        Urea; Any grade increase; n=4, 10, 5
    0
    0
    0
        Urea; Increase to Grade 3; n=4, 10, 5
    0
    0
    0
        Urea; Increase to Grade 4; n=4, 10, 5
    0
    0
    0
    Notes
    [91] - All Treated Population
    [92] - All Treated Population
    [93] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with grade change from Baseline in clinical chemistry data-Part 2

    Close Top of page
    End point title
    Number of participants with grade change from Baseline in clinical chemistry data-Part 2 [94] [95]
    End point description
    Blood samples were collected for the analysis of clinical chemistry parameters: glucose, albumin, ALP, ALT, amylase, AST, Dir bil, bilirubin, NT-BNP, calcium, cholesterol, CK, chloride, CO2, creatinine, GGT, HDL and LDL cholesterol, insulin, potassium, LDH, lipase, magnesium, protein, sodium, thyroxine, testosterone, triglycerides (triglyc), troponin I and T, urate and urea. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life–threatening consequences; Grade 5: death. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post-Baseline is presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.41 months of drug exposure
    Notes
    [94] - 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 statistical analysis was performed
    [95] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 2: Participants with NMC Part 2: Participants with SCLC Part 2: Participants with CRPC Part 2: Participants with TNBC Part 2: Participants with ER+BC Part 2: Participants with GIST
    Number of subjects analysed
    12 [96]
    14 [97]
    23 [98]
    19 [99]
    21 [100]
    13 [101]
    Units: Participants
        Glucose; Any grade increase; n=11,13,23,19,21,12
    10
    10
    20
    16
    18
    9
        Glucose; Increase to Grade 3; n=11,13,23,19,21,12
    0
    0
    0
    0
    1
    2
        Glucose; Increase to Grade 4; n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        Albumin; Any grade increase; n=11,13,23,19,21,12
    5
    6
    9
    8
    7
    5
        Albumin; Increase to Grade 3; n=11,13,23,19,21,12
    0
    0
    0
    0
    1
    0
        Albumin; Increase to Grade 4; n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        ALP; Any grade increase; n=11,13,23,19,21,12
    3
    1
    6
    3
    4
    4
        ALP; Increase to Grade 3; n=11,13,23,19,21,12
    0
    0
    2
    0
    0
    0
        ALP; Increase to Grade 4; n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        ALT; Any grade increase; n=11,14,23,19,21,12
    3
    6
    6
    5
    12
    3
        ALT; Increase to Grade 3; n=11,14,23,19,21,12
    0
    1
    0
    0
    0
    0
        ALT; Increase to Grade 4; n=11,14,23,19,21,12
    0
    0
    0
    0
    0
    0
        Amylase; Any grade increase; n=11,12,22,19,20,12
    5
    5
    9
    5
    6
    1
        Amylase; Increase to Grade 3; n=11,12,22,19,20,12
    1
    2
    2
    2
    2
    0
        Amylase; Increase to Grade 4; n=11,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        AST; Any grade increase; n=11,13,23,19,21,12
    3
    5
    10
    8
    14
    6
        AST; Increase to Grade 3; n=11,13,23,19,21,12
    0
    0
    1
    1
    3
    0
        AST; Increase to Grade 4; n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        Dir bil; Any grade increase; n=11,13,23,19,20,12
    0
    0
    0
    0
    0
    0
        Dir bil; Increase to Grade 3; n=11,13,23,19,20,12
    0
    0
    0
    0
    0
    0
        Dir bil; Increase to Grade 4; n=11,13,23,19,20,12
    0
    0
    0
    0
    0
    0
        Bilirubin;Any grade increase;n=11,14,23,19,21,12
    8
    10
    13
    6
    13
    4
        Bilirubin;Increase to Grade 3; n=11,14,23,19,21,12
    1
    1
    2
    0
    3
    0
        Bilirubin;Increase to Grade 4; n=11,14,23,19,21,12
    0
    0
    0
    0
    0
    0
        NT-BNP; Any grade increase; n=11,12,22,17,15,12
    0
    0
    0
    0
    0
    0
        NT-BNP; Increase to Grade 3; n=11,12,22,17,15,12
    0
    0
    0
    0
    0
    0
        NT-BNP; Increase to Grade 4; n=11,12,22,17,15,12
    0
    0
    0
    0
    0
    0
        Calcium; Any grade increase; n=11,13,23,19,21,12
    6
    3
    8
    4
    3
    3
        Calcium; Increase to Grade 3; n=11,13,23,19,21,12
    1
    0
    2
    0
    1
    0
        Calcium; Increase to Grade 4; n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        Cholesterol;Any grade increase;n=10,12,22,19,20,12
    5
    2
    2
    2
    9
    5
        Cholesterol;Increase to Grade3;n=10,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        Cholesterol;Increase to Grade4;n=10,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        CK; Any grade increase; n=9,9,21,17,18,11
    3
    2
    4
    0
    7
    5
        CK; Increase to Grade 3; n=9,9,21,17,18,11
    0
    0
    0
    0
    0
    0
        CK; Increase to Grade 4; n=9,9,21,17,18,11
    0
    0
    0
    0
    0
    0
        Chloride; Any grade increase; n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        Chloride; Increase to Grade 3; n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        Chloride; Increase to Grade 4; n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        CO2; Any grade increase; n=11,12,23,19,21,12
    0
    0
    0
    0
    0
    0
        CO2; Increase to Grade 3; n=11,12,23,19,21,12
    0
    0
    0
    0
    0
    0
        CO2; Increase to Grade 4; n=11,12,23,19,21,12
    0
    0
    0
    0
    0
    0
        Creatinine;Any grade increase;n=11,14,23,19,21,12
    3
    4
    9
    2
    6
    3
        Creatinine;Increase to Grade3;n=11,14,23,19,21,12
    0
    0
    2
    0
    0
    0
        Creatinine;Increase to Grade4;n=11,14,23,19,21,12
    0
    0
    1
    0
    0
    0
        GGT; Any grade increase; n=11,13,22,19,20,12
    0
    3
    7
    5
    6
    1
        GGT; Increase to Grade 3; n=11,13,22,19,20,12
    0
    0
    2
    2
    3
    0
        GGT; Increase to Grade 4; n=11,13,22,19,20,12
    0
    0
    0
    0
    1
    0
        HDL; Any grade increase; n=10,10,22,19,19,12
    0
    0
    0
    0
    0
    0
        HDL; Increase to Grade 3; n=10,10,22,19,19,12
    0
    0
    0
    0
    0
    0
        HDL; Increase to Grade 4;n=10,10,22,19,19,12
    0
    0
    0
    0
    0
    0
        Insulin; Any grade increase; n=11,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        Insulin; Increase to Grade 3; n=11,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        Insulin; Increase to Grade 4; n=11,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        Potassium; Any grade increase; n=11,14,23,19,21,12
    6
    4
    10
    5
    7
    7
        Potassium;Increase to Grade3;n=11,14,23,19,21,12
    0
    0
    1
    0
    0
    1
        Potassium;Increase to Grade4;n=11,14,23,19,21,12
    0
    0
    0
    0
    0
    0
        LDL; Any grade increase; n=10,10,22,19,19,12
    0
    0
    0
    0
    0
    0
        LDL; Increase to Grade 3; n=10,10,22,19,19,12
    0
    0
    0
    0
    0
    0
        LDL; Increase to Grade 4;n=10,10,22,19,19,12
    0
    0
    0
    0
    0
    0
        Lipase; Any grade increase; n=11,12,22,19,20,12
    3
    5
    7
    5
    4
    2
        Lipase; Increase to Grade 3;n=11,12,22,19,20,12
    2
    3
    0
    1
    0
    0
        Lipase; Increase to Grade 4;n=11,12,22,19,20,12
    0
    0
    0
    1
    1
    0
        Magnesium; Any grade increase; n=11,12,22,19,21,12
    2
    2
    5
    1
    4
    1
        Magnesium; Increase to Grade 3;n=11,12,22,19,21,12
    0
    0
    0
    0
    0
    0
        Magnesium; Increase to Grade4;n=11,12,22,19,21,12
    0
    0
    0
    0
    0
    0
        Protein; Any grade increase; n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        Protein; Increase to Grade 3;n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        Protein; Increase to Grade 4;n=11,13,23,19,21,12
    0
    0
    0
    0
    0
    0
        Sodium; Any grade increase; n=11, 14,23,19,21,12
    5
    5
    8
    5
    4
    5
        Sodium; Increase to Grade 3; n=11, 14,23,19,21,12
    0
    1
    1
    2
    0
    2
        Sodium; Increase to Grade 4; n=11, 14,23,19,21,12
    1
    0
    0
    0
    0
    0
        Thyroxine; Any grade increase;n=7,7,20,15,18,8
    0
    0
    0
    0
    0
    0
        Thyroxine; Increase to Grade3;n=7,7,20,15,18,8
    0
    0
    0
    0
    0
    0
        Thyroxine; Increase to Grade4;n=7,7,20,15,18,8
    0
    0
    0
    0
    0
    0
        Testosterone; Any grade increase; n=4,3,18,0,1,5
    0
    0
    0
    0
    0
    0
        Testosterone; Increase to Grade3; n=4,3,18,0,1,5
    0
    0
    0
    0
    0
    0
        Testosterone; Increase to Grade4; n=4,3,18,0,1,5
    0
    0
    0
    0
    0
    0
        Triglyc;Any grade increase;n=10,12,22,19,20,12
    7
    7
    15
    10
    11
    8
        Triglyc;Increase to Grade3;n=10,12,22,19,20,12
    1
    0
    4
    0
    1
    0
        Triglyc;Increase to Grade4;n=10,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        Troponin I; Any grade increase; n=7,6,15,15,14,7
    0
    0
    0
    0
    0
    0
        Troponin I; Increase to Grade 3; n=7,6,15,15,14,7
    0
    0
    0
    0
    0
    0
        Troponin I; Increase to Grade 4; n=7,6,15,15,14,7
    0
    0
    0
    0
    0
    0
        Troponin T;Any grade increase;n=11,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        Troponin T;Increase to Grade3;n=11,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        Troponin T;Increase to Grade4;n=11,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        Urate; Any grade increase; n=11,12,22,19,20,12
    0
    0
    2
    0
    0
    2
        Urate; Increase to Grade 3; n=11,12,22,19,20,12
    0
    0
    0
    0
    0
    0
        Urate; Increase to Grade 4; n=11,12,22,19,20,12
    0
    0
    2
    0
    0
    2
        Urea; Any grade increase; n=11,14,23,17,17,11
    0
    0
    0
    0
    0
    0
        Urea; Increase to Grade 3; n=11,14,23,17,17,11
    0
    0
    0
    0
    0
    0
        Urea; Increase to Grade 4;n=11,14,23,17,17,11
    0
    0
    0
    0
    0
    0
    Notes
    [96] - All Treated Population
    [97] - All Treated Population
    [98] - All Treated Population
    [99] - All Treated Population
    [100] - All Treated Population
    [101] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with grade change from Baseline in clinical chemistry data-Besylate sub-study

    Close Top of page
    End point title
    Number of participants with grade change from Baseline in clinical chemistry data-Besylate sub-study [102] [103]
    End point description
    Blood samples were collected for the analysis of clinical chemistry parameters: glucose, albumin, ALP, ALT, amylase, AST, Dir bil, bilirubin, NT-BNP, calcium, cholesterol, CK, chloride, CO2, creatinine, GGT, HDL and LDL cholesterol, insulin, potassium, LDH, lipase, magnesium, protein, sodium, thyroxine, testosterone, triglycerides, troponin I and T, urate and urea. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life–threatening consequences; Grade 5: death. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.87 months of drug exposure
    Notes
    [102] - 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 statistical analysis was performed
    [103] - 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: The end point is specific for Part 1 QD dosing
    End point values
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Number of subjects analysed
    5 [104]
    5 [105]
    Units: Participants
        Glucose; Any grade increase; n=5,5
    4
    5
        Glucose; Increase to Grade 3; n=5,5
    0
    0
        Glucose; Increase to Grade 4; n=5,5
    0
    0
        Albumin; Any grade increase; n=5,5
    3
    3
        Albumin; Increase to Grade 3; n=5,5
    1
    0
        Albumin; Increase to Grade 4; n=5,5
    0
    0
        ALP; Any grade increase;n=5,5
    1
    0
        ALP; Increase to Grade 3;n=5,5
    0
    0
        ALP; Increase to Grade 4;n=5,5
    0
    0
        ALT; Any grade increase;n=5,5
    1
    1
        ALT; Increase to Grade 3;n=5,5
    0
    0
        ALT; Increase to Grade 4; n=5,5
    0
    0
        Amylase; Any grade increase; n=5,5
    0
    0
        Amylase; Increase to Grade 3; n=5,5
    0
    0
        Amylase; Increase to Grade 4; n=5,5
    0
    0
        AST; Any grade increase; n=5,5
    2
    1
        AST; Increase to Grade 3;n=5,5
    0
    0
        AST; Increase to Grade 4; n=5,5
    0
    0
        Dir bil; Any grade increase; n=5,5
    0
    0
        Dir bil; Increase to Grade 3; n=5,5
    0
    0
        Dir bil; Increase to Grade 4; n=5,5
    0
    0
        Bilirubin; Any grade increase; n=5,5
    3
    4
        Bilirubin; Increase to Grade 3; n=5,5
    1
    2
        Bilirubin; Increase to Grade 4; n=5,5
    0
    0
        NT-BNP; Any grade increase; n=5,5
    0
    0
        NT-BNP; Increase to Grade 3; n=5,5
    0
    0
        NT-BNP; Increase to Grade 4; n=5,5
    0
    0
        Calcium; Any grade increase; n=5,5
    1
    2
        Calcium; Increase to Grade 3; n=5,5
    0
    0
        Calcium; Increase to Grade 4; n=5,5
    0
    0
        Cholesterol; Any grade increase; n=5,3
    1
    0
        Cholesterol; Increase to Grade 3; n=5,3
    0
    0
        Cholesterol; Increase to Grade 4; n=5,3
    0
    0
        CK; Any grade increase; n=5,5
    2
    0
        CK; Increase to Grade 3; n=5,5
    0
    0
        CK; Increase to Grade 4; n=5,5
    0
    0
        Chloride; Any grade increase; n=5,5
    0
    0
        Chloride; Increase to Grade 3; n=5,5
    0
    0
        Chloride; Increase to Grade 4; n=5,5
    0
    0
        CO2; Any grade increase; n=5,5
    0
    0
        CO2; Increase to Grade 3;n=5,5
    0
    0
        CO2; Increase to Grade 4;n=5,5
    0
    0
        Creatinine; Any grade increase; n=5,5
    1
    1
        Creatinine; Increase to Grade 3; n=5,5
    0
    0
        Creatinine; Increase to Grade 4; n=5,5
    0
    0
        GGT; Any grade increase; n=5,5
    0
    0
        GGT; Increase to Grade 3;n=5,5
    0
    0
        GGT; Increase to Grade 4;n=5,5
    0
    0
        HDL; Any grade increase;n=5,3
    0
    0
        HDL; Increase to Grade 3; n=5,3
    0
    0
        HDL; Increase to Grade 4; n=5,3
    0
    0
        Insulin; Any grade increase; n=5,5
    0
    0
        Insulin; Increase to Grade 3; n=5,5
    0
    0
        Insulin; Increase to Grade 4; n=5,5
    0
    0
        Potassium; Any grade increase; n=5,5
    3
    3
        Potassium; Increase to Grade 3; n=5,5
    0
    0
        Potassium; Increase to Grade 4; n=5,5
    0
    0
        LDL; Any grade increase; n=5,3
    0
    0
        LDL; Increase to Grade 3; n=5,3
    0
    0
        LDL; Increase to Grade 4; n=5,3
    0
    0
        Lipase; Any grade increase; n=5,4
    0
    0
        Lipase; Increase to Grade 3; n=5,4
    0
    0
        Lipase; Increase to Grade 4;n=5,4
    0
    0
        Magnesium; Any grade increase;n=5,5
    2
    1
        Magnesium; Increase to Grade 3; n=5,5
    0
    1
        Magnesium; Increase to Grade 4;n=5,5
    0
    0
        Protein; Any grade increase; n=5,5
    0
    0
        Protein; Increase to Grade 3; n=5,5
    0
    0
        Protein; Increase to Grade 4; n=5,5
    0
    0
        Sodium; Any grade increase; n=5,5
    2
    3
        Sodium; Increase to Grade 3; n=5,5
    0
    1
        Sodium; Increase to Grade 4; n=5,5
    0
    0
        Thyroxine; Any grade increase; n=5,3
    0
    0
        Thyroxine; Increase to Grade 3; n=5,3
    0
    0
        Thyroxine; Increase to Grade 4; n=5,3
    0
    0
        Testosterone; Any grade increase; n=2,1
    0
    0
        Testosterone; Increase to Grade 3; n=2,1
    0
    0
        Testosterone; Increase to Grade 4; n=2,1
    0
    0
        Triglycerides; Any grade increase; n=5,3
    1
    2
        Triglycerides; Increase to Grade 3; n=5,3
    0
    0
        Triglycerides; Increase to Grade 4; n=5,3
    0
    0
        Troponin I; Any grade increase; n=1,0
    0
    99999
        Troponin I; Increase to Grade 3; n=1,0
    0
    99999
        Troponin I; Increase to Grade 4; n=1,0
    0
    99999
        Troponin T; Any grade increase; n=5,5
    0
    0
        Troponin T; Increase to Grade 3; n=5,5
    0
    0
        Troponin T; Increase to Grade 4; n=5,5
    0
    0
        Urate; Any grade increase; n=5,5
    0
    0
        Urate; Increase to Grade 3; n=5,5
    0
    0
        Urate; Increase to Grade 4; n=5,5
    0
    0
        Urea; Any grade increase;n=5,5
    0
    0
        Urea; Increase to Grade 3;n=5,5
    0
    0
        Urea; Increase to Grade 4;n=5,5
    0
    0
    Notes
    [104] - All treated Population
    [105] - All treated Population
    No statistical analyses for this end point

    Primary: Number of participants with grade change from Baseline in hematology data-Part 1 QD

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    End point title
    Number of participants with grade change from Baseline in hematology data-Part 1 QD [106] [107]
    End point description
    Blood samples were collected for the analysis of hematology parameters: activated partial thromboplastin time (aPTT), platelet count, red blood cell count (RBC), white blood cell count (WBC), prothrombin international normalized ratio (INR), prothrombin time (PT), fibrinogen (Fib), hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life–threatening consequences; Grade 5: death. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.38 months of drug exposure
    Notes
    [106] - 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 statistical analysis was performed
    [107] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [108]
    4 [109]
    1 [110]
    3 [111]
    4 [112]
    9 [113]
    32 [114]
    9 [115]
    Units: Participants
        Basophils; Any grade increase; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Basophils; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Basophils; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Eosinophils; Any grade increase;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Eosinophils; Increase to Grade3;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Eosinophils; Increase to Grade4;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Hemoglobin;Any grade increase;n=4,9,32,9,2,4,1,3
    1
    1
    0
    2
    2
    2
    21
    7
        Hemoglobin;Increase to Grade3;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    1
    1
    9
    1
        Hemoglobin;Increase to Grade4;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        INR;Any grade increase;n=4,9,32,9,2,4,1,3
    2
    2
    1
    0
    0
    1
    21
    2
        INR;Increase to Grade 3;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        INR;Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Lymphocytes;Any grade increase;n=4,9,32,9,2,4,1,3
    1
    2
    1
    0
    2
    5
    19
    4
        Lymphocytes; Increase to Grade3;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    2
    8
    1
        Lymphocytes; Increase to Grade4;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    1
    1
        Monocytes; Any grade increase;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Monocytes;Increase to Grade3;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Monocytes; Increase to Grade4;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Neutrophils; Any grade increase;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    7
    3
        Neutrophils; Increase to Grade3;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    1
        Neutrophils; Increase to Grade4;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    1
    0
        Platelets; Any grade increase;n=4,9,32,9,2,4,1,3
    0
    1
    0
    0
    2
    5
    26
    8
        Platelets; Increase to Grade3;n=4,9,32,9,2,4,1,3
    0
    1
    0
    0
    0
    0
    11
    5
        Platelets; Increase to Grade4;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    1
    5
    2
        PT; Any grade increase;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        PT; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        PT; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        RBC; Any grade increase; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        RBC; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        RBC; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        WBC; Any grade increase; n=4,9,32,9,2,4,1,3
    0
    1
    0
    0
    0
    3
    11
    5
        WBC; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    1
        WBC; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    1
    0
        Fib; Any grade increase;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    4
    0
        Fib; Increase to Grade 3;n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        Fib; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
        aPTT; Any grade increase; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    14
    2
        aPTT; Increase to Grade 3; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    1
    0
        aPTT; Increase to Grade 4; n=4,9,32,9,2,4,1,3
    0
    0
    0
    0
    0
    0
    0
    0
    Notes
    [108] - All Treated Population
    [109] - All Treated Population
    [110] - All Treated Population
    [111] - All Treated Population
    [112] - All Treated Population
    [113] - All Treated Population
    [114] - All Treated Population
    [115] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with grade change from Baseline in hematology data-Part 1 BID

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    End point title
    Number of participants with grade change from Baseline in hematology data-Part 1 BID [116] [117]
    End point description
    Blood samples were collected for the analysis of hematology parameters: aPTT, platelet count, RBC, WBC, INR, PT, Fib, hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life–threatening consequences; Grade 5: death. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.41 months of drug exposure
    Notes
    [116] - 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 statistical analysis was performed
    [117] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [118]
    10 [119]
    5 [120]
    Units: Participants
        Basophils; Any grade increase; n=4,10,5
    0
    0
    0
        Basophils; Increase to Grade 3; n=4,10,5
    0
    0
    0
        Basophils; Increase to Grade 4; n=4,10,5
    0
    0
    0
        Eosinophils; Any grade increase; n=4,10,5
    0
    0
    0
        Eosinophils; Increase to Grade3; n=4,10,5
    0
    0
    0
        Eosinophils; Increase to Grade4; n=4,10,5
    0
    0
    0
        Hemoglobin; Any grade increase; n=4,10,5
    4
    8
    4
        Hemoglobin; Increase to Grade 3; n=4,10,5
    0
    3
    2
        Hemoglobin; Increase to Grade 4; n=4,10,5
    0
    0
    0
        INR; Any grade increase; n=4,10,5
    0
    6
    3
        INR; Increase to Grade 3; n=4,10,5
    0
    0
    0
        INR; Increase to Grade 4; n=4,10,5
    0
    0
    0
        Lymphocytes; Any grade increase; n=4,10,5
    2
    8
    2
        Lymphocytes; Increase to Grade3; n=4,10,5
    0
    4
    0
        Lymphocytes; Increase to Grade4; n=4,10,5
    0
    0
    0
        Monocytes; Any grade increase; n=4,10,5
    0
    0
    0
        Monocytes;Increase to Grade3; n=4,10,5
    0
    0
    0
        Monocytes; Increase to Grade 4; n=4,10,5
    0
    0
    0
        Neutrophils; Any grade increase; n=4,10,5
    0
    0
    1
        Neutrophils; Increase to Grade 3; n=4,10,5
    0
    0
    0
        Neutrophils; Increase to Grade 4; n=4,10,5
    0
    0
    0
        Platelets; Any grade increase; n=4,10,5
    1
    10
    5
        Platelets; Increase to Grade 3; n=4,10,5
    0
    2
    2
        Platelets; Increase to Grade 4; n=4,10,5
    0
    0
    1
        PT; Any grade increase;n=4,10,5
    0
    0
    0
        PT; Increase to Grade 3; n=4,10,5
    0
    0
    0
        PT; Increase to Grade 4; n=4,10,5
    0
    0
    0
        RBC; Any grade increase; n=4,10,5
    0
    0
    0
        RBC; Increase to Grade 3; n=4,10,5
    0
    0
    0
        RBC; Increase to Grade 4; n=4,10,5
    0
    0
    0
        WBC; Any grade increase; n=4,10,5
    1
    0
    1
        WBC; Increase to Grade 3; n=4,10,5
    0
    0
    0
        WBC; Increase to Grade 4; n=4,10,5
    0
    0
    0
        Fib; Any grade increase; n=4,10,5
    0
    0
    0
        Fib; Increase to Grade 3; n=4,10,5
    0
    0
    0
        Fib; Increase to Grade 4; n=4,10,5
    0
    0
    0
        aPTT; Any grade increase; n=4,10,5
    0
    5
    2
        aPTT; Increase to Grade 3; n=4,10,5
    0
    0
    0
        aPTT; Increase to Grade 4; n=4,10,5
    0
    0
    0
    Notes
    [118] - All Treated Population
    [119] - All Treated Population
    [120] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with grade change from Baseline in hematology data-Part 2

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    End point title
    Number of participants with grade change from Baseline in hematology data-Part 2 [121]
    End point description
    Blood samples were collected for the analysis of hematology parameters: aPTT, platelet count, RBC, WBC, INR, PT, Fib, hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life–threatening consequences; Grade 5: death. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.41 months of drug exposure
    Notes
    [121] - 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 statistical analysis was performed
    End point values
    Participants with NMC Participants with SCLC Participants with CRPC Participants with TNBC Participants with ER+BC Participants with GIST
    Number of subjects analysed
    12 [122]
    14 [123]
    23 [124]
    19 [125]
    21 [126]
    13 [127]
    Units: Participants
        Basophils; Any grade increase; n=11,13,23,19,21,13
    0
    0
    0
    0
    0
    0
        Basophils; Increase to Grade3; n=11,13,23,19,21,13
    0
    0
    0
    0
    0
    0
        Basophils; Increase to Grade4; n=11,13,23,19,21,13
    0
    0
    0
    0
    0
    0
        Eosinophils;Any grade increase;n=11,13,23,19,21,13
    0
    0
    0
    0
    0
    0
        Eosinophils;Increase to Grade3;n=11,13,23,19,21,13
    0
    0
    0
    0
    0
    0
        Eosinophils;Increase to Grade4;n=11,13,23,19,21,13
    0
    0
    0
    0
    0
    0
        Hemoglobin;Any grade increase;n=11,14,23,19,21,13
    6
    10
    18
    10
    18
    6
        Hemoglobin;Increase to Grade3;n=11,14,23,19,21,13
    3
    2
    9
    4
    5
    3
        Hemoglobin;Increase to Grade4;n=11,14, 23,19,21,13
    0
    0
    0
    0
    0
    0
        INR; Any grade increase; n=11,12,21,17,18,12
    8
    6
    13
    8
    11
    7
        INR; Increase to Grade3; n=11,12,21,17,18,12
    0
    0
    0
    0
    0
    0
        INR; Increase to Grade4; n=11,12,21,17,18,12
    0
    0
    0
    0
    0
    0
        Lymphocytes;Any grade increase;n=11,13,23,19,21,13
    8
    7
    14
    9
    13
    6
        Lymphocytes;Increase to Grade3;n=11,13,23,19,21,13
    2
    2
    6
    2
    1
    0
        Lymphocytes;Increase to Grade4;n=11,13,23,19,21,13
    0
    1
    0
    0
    0
    0
        Monocytes; Any grade increase; n=11,13,23,19,21,13
    0
    0
    0
    0
    0
    0
        Monocytes;Increase to Grade3; n=11,13,23,19,21,13
    0
    0
    0
    0
    0
    0
        Monocytes; Increase to Grade4; n=11,13,23,19,21,13
    0
    0
    0
    0
    0
    0
        Neutrophils;Any grade increase;n=11,14,23,19,21,13
    4
    4
    8
    3
    6
    1
        Neutrophils;Increase to Grade3;n=11,14,23,19,21,13
    1
    1
    0
    2
    1
    0
        Neutrophils;Increase to Grade4;n=11,14,23,19,21,13
    0
    0
    0
    0
    0
    0
        Platelets; Any grade increase; n=11,14,23,19,21,13
    7
    12
    20
    17
    18
    7
        Platelets; Increase to Grade3; n=11,14,23,19,21,13
    4
    4
    5
    6
    6
    0
        Platelets; Increase to Grade4; n=11,14,23,19,21,13
    2
    3
    8
    4
    2
    0
        PT; Any grade increase;n=10,10, 18, 17, 18, 12
    0
    0
    0
    0
    0
    0
        PT; Increase to Grade 3; n=10,10, 18, 17, 18, 12
    0
    0
    0
    0
    0
    0
        PT; Increase to Grade 4; n=10,10, 18, 17, 18, 12
    0
    0
    0
    0
    0
    0
        RBC; Any grade increase; n=11, 13, 23, 19, 21, 13
    0
    0
    0
    0
    0
    0
        RBC; Increase to Grade 3; n=11, 13, 23, 19, 21, 13
    0
    0
    0
    0
    0
    0
        RBC; Increase to Grade 4; n=11, 13, 23, 19, 21, 13
    0
    0
    0
    0
    0
    0
        WBC; Any grade increase; n=11, 14, 23, 19, 21, 13
    7
    5
    9
    5
    6
    3
        WBC; Increase to Grade 3; n=11, 14, 23, 19, 21, 13
    1
    0
    1
    1
    0
    0
        WBC; Increase to Grade 4; n=11, 14, 23, 19, 21, 13
    0
    0
    0
    0
    0
    0
        Fib; Any grade increase; n=11, 11, 21, 17, 18, 12
    2
    0
    1
    0
    0
    1
        Fib; Increase to Grade 3; n=11, 11, 21, 17, 18, 12
    1
    0
    0
    0
    0
    0
        Fib; Increase to Grade 4; n=11, 11, 21, 17, 18, 12
    0
    0
    0
    0
    0
    0
        aPTT; Any grade increase; n=11,12,21,17,18,12
    4
    4
    1
    3
    5
    4
        aPTT; Increase to Grade3; n=11,12,21, 17, 18, 12
    0
    0
    0
    1
    0
    0
        aPTT; Increase to Grade4; n=11,12,21,17,18,12
    0
    0
    0
    0
    0
    0
    Notes
    [122] - All Treated Population
    [123] - All Treated Population
    [124] - All Treated Population
    [125] - All Treated Population
    [126] - All Treated Population
    [127] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with grade change from Baseline in hematology data-Besylate sub-study

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    End point title
    Number of participants with grade change from Baseline in hematology data-Besylate sub-study [128] [129]
    End point description
    Blood samples were collected for the analysis of hematology parameters: aPTT, platelet count, RBC, WBC, INR, PT, Fib, hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life–threatening consequences; Grade 5: death. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.87 months of drug exposure
    Notes
    [128] - 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 statistical analysis was performed
    [129] - 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: The end point is specific for Part 1 QD dosing
    End point values
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Number of subjects analysed
    5 [130]
    5 [131]
    Units: Participants
        Basophils; Any grade increase
    0
    0
        Basophils; Increase to Grade 3
    0
    0
        Basophils; Increase to Grade 4
    0
    0
        Eosinophils; Any grade increase
    0
    0
        Eosinophils; Increase to Grade 3
    0
    0
        Eosinophils; Increase to Grade 4
    0
    0
        Hemoglobin; Any grade increase
    4
    3
        Hemoglobin; Increase to Grade 3
    2
    2
        Hemoglobin; Increase to Grade 4
    0
    0
        INR; Any grade increase
    1
    1
        INR; Increase to Grade 3
    0
    0
        INR; Increase to Grade 4
    0
    0
        Lymphocytes; Any grade increase
    3
    4
        Lymphocytes; Increase to Grade 3
    1
    0
        Lymphocytes; Increase to Grade 4
    2
    0
        Monocytes; Any grade increase
    0
    0
        Monocytes; Increase to Grade 3
    0
    0
        Monocytes; Increase to Grade 4
    0
    0
        Neutrophils; Any grade increase
    1
    1
        Neutrophils; Increase to Grade 3
    0
    0
        Neutrophils; Increase to Grade 4
    0
    0
        Platelets; Any grade increase
    5
    5
        Platelets; Increase to Grade 3
    0
    2
        Platelets; Increase to Grade 4
    3
    1
        PT; Any grade increase
    0
    0
        PT; Increase to Grade 3
    0
    0
        PT; Increase to Grade 4
    0
    0
        RBC; Any grade increase
    0
    0
        RBC; Increase to Grade 3
    0
    0
        RBC; Increase to Grade 4
    0
    0
        WBC; Any grade increase
    3
    1
        WBC; Increase to Grade 3
    0
    0
        WBC; Increase to Grade 4
    0
    0
        Fib; Any grade increase
    0
    0
        Fib; Increase to Grade 3
    0
    0
        Fib; Increase to Grade 4
    0
    0
        aPTT; Any grade increase
    4
    2
        aPTT; Increase to Grade 3
    0
    0
        aPTT; Increase to Grade 4
    0
    0
    Notes
    [130] - All treated Population
    [131] - All treated Population
    No statistical analyses for this end point

    Primary: Number of participants with maximum urinalysis change from Baseline-Part 1 QD

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    End point title
    Number of participants with maximum urinalysis change from Baseline-Part 1 QD [132] [133]
    End point description
    Urine samples were collected for the analysis of following urine parameters: potential of hydrogen (pH), glucose, protein, occult blood, ketones, specific gravity, erythrocytes and leukocytes. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Only parameters and time points with non-zero values for any increase have been presented. 99999 indicates data was not available due to insufficient participants. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and Weeks 5, 9, 17, 25, 33, 41, 49 and discharge/progression (disc/prog)
    Notes
    [132] - 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 statistical analysis was performed
    [133] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [134]
    4 [135]
    1 [136]
    3 [137]
    4 [138]
    9 [139]
    32 [140]
    9 [141]
    Units: Participants
        Cellular casts; Week 9; n=0,1,4,1,0,0,0,0
    99999
    99999
    99999
    99999
    99999
    0
    1
    1
        Cellular casts; Week 17; n=0,0,1,0,0,0,0,0
    99999
    99999
    99999
    99999
    99999
    99999
    1
    99999
        Cellular casts; Disc/Prog; n=0,1,5,1,0,0,0,0
    99999
    99999
    99999
    99999
    99999
    0
    1
    0
        Hyaline casts;Week 5; n=1,2,5,3,0,1,0,0
    99999
    0
    99999
    99999
    0
    0
    2
    1
        Hyaline casts;Week 9; n=0,1,5,3,0,1,0,0
    99999
    0
    99999
    99999
    99999
    0
    0
    1
        Glucose;Week 5; n=2,7,20,7,1,2,1,3
    0
    0
    0
    0
    0
    0
    4
    2
        Glucose;Week 9; n=1,3,12,5,1,1,0,1
    0
    0
    99999
    0
    0
    0
    1
    1
        Glucose;Week 25; n=0,0,3,1,0,1,0,0
    99999
    0
    99999
    99999
    99999
    99999
    0
    1
        Glucose;Disc/Prog; n=0,3,17,2,0,1,0,1
    99999
    0
    99999
    1
    99999
    0
    1
    0
        Ketones;Week 5; n=2,7,20,7,1,2,1,3
    0
    0
    0
    0
    0
    0
    2
    1
        Ketones;Week 9; n=1,3,12,5,1,1,0,1
    0
    0
    99999
    0
    0
    0
    2
    0
        Occult blood;Week 5; n=2,7,17,7,1,2,1,3
    0
    0
    0
    1
    2
    0
    2
    0
        Occult blood;Week 9; n=1,3,11,5,1,1,0,1
    0
    0
    99999
    0
    0
    0
    3
    0
        Occult blood;Week 17; n=0,0,5,3,0,1,0,0
    99999
    0
    99999
    99999
    99999
    99999
    1
    0
        Occult blood;Week 25; n=0,0,3,1,0,1,0,0
    99999
    0
    99999
    99999
    99999
    99999
    1
    0
        Occult blood;Week 33; n=0,0,2,0,0,1,0,0
    99999
    0
    99999
    99999
    99999
    99999
    1
    99999
        Occult blood;Disc/Prog; n=0,3,17,2,0,1,0,1
    99999
    0
    99999
    0
    99999
    0
    2
    0
        pH;Week 5; n=2,7,20,7,1,2,1,3
    0
    0
    0
    1
    0
    5
    6
    3
        pH;Week 9; n=1,3,12,5,1,1,0,1
    0
    1
    99999
    1
    0
    2
    8
    2
        pH;Week 25; n=0,0,3,1,0,1,0,0
    99999
    1
    99999
    99999
    99999
    99999
    1
    1
        pH;Week 33; n=0,0,2,0,0,1,0,0
    99999
    1
    99999
    99999
    99999
    99999
    0
    99999
        pH;Disc/Prog; n=0,3,17,2,0,1,0,1
    99999
    1
    99999
    0
    99999
    1
    9
    1
        Protein;Week 5; n=2,7,20,7,1,2,1,3
    0
    0
    0
    0
    0
    3
    9
    4
        Protein;Week 9; n=1,3,12,5,1,1,0,1
    0
    1
    99999
    0
    0
    1
    7
    3
        Protein;Week 17; n=0,0,5,3,0,1,0,0
    99999
    0
    99999
    99999
    99999
    99999
    1
    0
        Protein;Week 25; n=0,0,3,1,0,1,0,0
    99999
    0
    99999
    99999
    99999
    99999
    1
    0
        Protein;Disc/Prog; n=0,3,17,2,0,1,0,1
    99999
    0
    99999
    0
    99999
    0
    5
    1
        Specific gravity;Week 5; n=2,7,20,7,1,2,1,3
    1
    1
    0
    2
    2
    5
    7
    5
        Specific gravity;Week 9; n=1,3,12,5,1,1,0,1
    1
    0
    99999
    0
    0
    2
    6
    4
        Specific gravity;Week 17; n=0,0,5,3,0,1,0,0
    99999
    1
    99999
    99999
    99999
    99999
    4
    2
        Specific gravity;Week 25; n=0,0,3,1,0,1,0,0
    99999
    1
    99999
    99999
    99999
    99999
    1
    0
        Specific gravity;Week 33; n=0,0,2,0,0,1,0,0
    99999
    1
    99999
    99999
    99999
    99999
    1
    99999
        Specific gravity;Disc/Prog; n=0,3,16,2,0,1,0,1
    99999
    1
    99999
    1
    99999
    1
    6
    1
        Specific gravity;Week 41; n=0,0,1,0,0,0,0,0
    99999
    99999
    99999
    99999
    99999
    99999
    1
    99999
        Specific gravity;Week 49; n=0,0,1,0,0,0,0,0
    99999
    99999
    99999
    99999
    99999
    99999
    1
    99999
        Leukocytes;Week 5; n=2,6,11,6,1,2,1,2
    0
    0
    0
    0
    1
    2
    4
    2
        Leukocytes;Week 9; n=1,1,6,4,1,1,0,1
    0
    0
    99999
    0
    1
    0
    3
    1
        Leukocytes;Week 17; n=0,0,1,2,0,1,0,0
    99999
    0
    99999
    99999
    99999
    99999
    1
    0
        Leukocytes;Disc/Prog; n=0,2,6,1,0,1,0,1
    99999
    0
    99999
    0
    99999
    0
    4
    1
    Notes
    [134] - All Treated Population
    [135] - All Treated Population
    [136] - All Treated Population
    [137] - All Treated Population
    [138] - All Treated Population
    [139] - All Treated Population
    [140] - All Treated Population
    [141] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with maximum urinalysis change from Baseline data-Part 1 BID

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    End point title
    Number of participants with maximum urinalysis change from Baseline data-Part 1 BID [142] [143]
    End point description
    Urine samples were collected for the analysis of following urine parameters: pH, glucose, protein, occult blood, ketones, specific gravity, erythrocytes and leukocytes. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Only parameters and time points with non-zero values for any increase have been presented. 99999 indicates data was not available due to insufficient participants. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and Weeks 5,9,17 and discharge/progression
    Notes
    [142] - 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 statistical analysis was performed
    [143] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [144]
    10 [145]
    5 [146]
    Units: Participants
        Glucose; Week 5;n=2,7,3
    0
    0
    1
        Glucose; Week 9;n=0,4,2
    99999
    1
    0
        Glucose; Week 17;n=0,2,0
    99999
    1
    99999
        Glucose; disc/prog;n=0,6,1
    99999
    1
    0
        Ketones; Week 5;n=2,7,3
    0
    1
    0
        Ketones; Week 17;n=0,2,0
    99999
    1
    99999
        Occult blood; Week 5;n=2,7,3
    0
    2
    0
        Occult blood; Week 9;n=0,4,2
    99999
    1
    0
        Occult blood; disc/prog;n=0,6,1
    99999
    2
    0
        pH; Week 5;n=2,7,3
    2
    4
    2
        pH; Week 9;n=0,4,2
    99999
    4
    1
        pH; Week 17;n=0,2,0
    99999
    1
    99999
        pH; disc/prog;n=0,7,1
    99999
    4
    1
        Protein; Week 5;n=2,7,3
    0
    3
    1
        Protein; Week 9;n=0,4,2
    99999
    2
    0
        Protein; Week 17;n=0,2,0
    99999
    2
    99999
        Protein; disc/prog;n=0,7,1
    99999
    1
    1
        Erythrocytes; Week 5;n=1,5,1
    1
    4
    1
        Erythrocytes; Week 9;n=0,1,1
    99999
    0
    1
        Erythrocytes; Week 17;n=0,1,0
    99999
    1
    99999
        Specific gravity; Week 5;n=2,7,3
    2
    1
    2
        Specific gravity; Week 9;n=0,4,2
    99999
    1
    1
        Specific gravity; Week 17;n=0,2,0
    99999
    1
    99999
        Specific gravity; disc/prog;n=0,7,1
    99999
    2
    0
        Leukocytes; Week 5;n=1,5,1
    0
    4
    1
        Leukocytes; Week 9;n=0,1,1
    99999
    0
    1
        Leukocytes; Week 17;n=0,1,0
    99999
    1
    99999
    Notes
    [144] - All Treated Population
    [145] - All Treated Population
    [146] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with maximum urinalysis change from Baseline-Part 2

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    End point title
    Number of participants with maximum urinalysis change from Baseline-Part 2 [147] [148]
    End point description
    Urine samples were collected for the analysis of following urine parameters: pH, glucose, protein, blood, ketones, specific gravity, erythrocytes and leukocytes. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Only parameters and time points with non-zero values for any increase have been presented. 99999 indicates data was not available due to insufficient participants. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1), Weeks 5,9,13,25,37, 49, 73, 85 and discharge/progression
    Notes
    [147] - 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 statistical analysis was performed
    [148] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 2: Participants with NMC Part 2: Participants with SCLC Part 2: Participants with CRPC Part 2: Participants with TNBC Part 2: Participants with ER+BC Part 2: Participants with GIST
    Number of subjects analysed
    12 [149]
    14 [150]
    23 [151]
    19 [152]
    21 [153]
    13 [154]
    Units: Participants
        Granular cast;Week5;n=0,2,2,1,3,0
    99999
    0
    0
    0
    1
    99999
        Granular cast;disc/prog;n=1,2,6,3,4,0
    0
    0
    2
    0
    0
    0
        Hyaline cast;Week5;n=1,2,2,2,4,0
    1
    0
    0
    1
    1
    99999
        Hyaline cast;Week9;n=0,0,1,2,1,1
    99999
    99999
    0
    0
    0
    1
        Hyaline cast;Week13;n=1,1,0,0,0,0
    0
    1
    99999
    99999
    99999
    99999
        Hyaline cast;disc/prog;n=1,2,6,3,4,0
    0
    0
    2
    0
    0
    99999
        Glucose;Week 5;n=8,7,18,12,14,8
    1
    2
    2
    0
    0
    1
        Glucose;Week9;n=8,3,12,3,6,5
    2
    1
    0
    0
    0
    0
        Glucose;Week13;n=7,2,6,1,2,2
    2
    1
    1
    0
    0
    0
        Glucose;Week37;n=3,0,1,0,0,0
    1
    99999
    0
    99999
    99999
    99999
        Glucose;Week49;n=1,0,1,0,0,0
    1
    99999
    0
    99999
    99999
    99999
        Glucose;Week73;n=1,0,0,0,0,0
    1
    99999
    99999
    99999
    99999
    99999
        Glucose;Week85;n=1,0,0,0,0,0
    1
    99999
    99999
    99999
    99999
    99999
        Glucose;disc/prog;n=3,6,16,12,12,5
    0
    0
    0
    0
    1
    0
        Ketones;Week5;n=8,7,18,12,14,8
    0
    1
    0
    0
    1
    0
        Ketones;Week9;n=8,3,12,3,6,5
    0
    1
    0
    0
    0
    0
        Ketones;disc/prog;n=3,6,16,12,12,5
    0
    1
    2
    0
    1
    0
        Occult blood;Week5;n=8,7,18,12,14,8
    1
    0
    5
    0
    0
    0
        Occult blood;Week9;n=8,3,12,3,6,5
    0
    1
    5
    0
    0
    0
        Occult blood;Week13;n=7,2,6,1,2,2
    1
    0
    0
    0
    0
    0
        Occult blood;Week25;n=2,0,3,0,0,0
    0
    99999
    1
    99999
    99999
    99999
        Occult blood;Week37;n=3,0,1,0,0,0
    1
    99999
    0
    99999
    99999
    99999
        Occult blood;disc/prog;n=3,6,16,12,12,5
    0
    0
    8
    0
    0
    0
        pH;Week5;n=8,7,18,12,14,8
    6
    3
    8
    3
    6
    3
        pH;Week9;n=8,3,12,3,6,5
    5
    1
    7
    2
    4
    2
        pH;Week13;n=7,2,6,1,2,2
    2
    1
    3
    1
    0
    1
        pH;Week25;n=2,0,3,0,0,0
    1
    99999
    1
    99999
    99999
    99999
        pH;Week37;n=3,0,1,0,0,0
    3
    99999
    0
    99999
    99999
    99999
        pH;Week49;n=1,0,1,0,0,0
    1
    99999
    0
    99999
    99999
    99999
        pH;Week73;n=1,0,0,0,0,0
    1
    99999
    99999
    99999
    99999
    99999
        pH;Week85;n=1,0,0,0,0,0
    1
    99999
    99999
    99999
    99999
    99999
        pH;disc/prog;n=3,6,16,12,12,5
    1
    2
    6
    6
    5
    2
        Protein;Week5;n=8,7,18,12,14,8
    1
    1
    9
    3
    5
    6
        Protein;Week9;n=8,3,12,3,6,5
    3
    2
    4
    0
    0
    3
        Protein;Week13;n=7,2,6,1,2,2
    3
    1
    2
    0
    0
    0
        Protein;Week37;n=1,0,1,0,0,0
    1
    99999
    0
    99999
    99999
    99999
        Protein;disc/prog;n=3,6,16,12,12,5
    1
    1
    6
    2
    3
    2
        Erythrocytes;Week5;n=3,3,8,4,4,4
    2
    0
    5
    2
    3
    2
        Erythrocytes;Week9;n=4,0,2,2,1,2
    2
    99999
    1
    1
    1
    1
        Erythrocytes;Week13;n=3,1,0,0,0,1
    3
    1
    99999
    99999
    99999
    0
        Erythrocytes;disc/prog;n=1,2,6,3,4,2
    0
    0
    5
    1
    2
    0
        Specific gravity;Week5;n=8,7,18,12,14,8
    4
    4
    2
    5
    7
    2
        Specific gravity;Week9;n=8,3,12,3,6,5
    2
    1
    2
    2
    5
    3
        Specific gravity;Week13;n=7,2,6,1,2,2
    2
    1
    1
    0
    0
    1
        Specific gravity;disc/prog;n=3,6,16,12,12,5
    0
    2
    3
    3
    5
    1
        Leukocytes;Week5;n=3,3,8,4,4,4
    1
    1
    5
    3
    4
    4
        Leukocytes;Week9;n=4,0,2,2,1,3
    0
    99999
    2
    1
    0
    3
        Leukocytes;Week13;n=3,1,0,0,0,1
    1
    0
    99999
    99999
    99999
    0
        Leukocytes;Week25;n=2,0,1,0,0,0
    0
    99999
    1
    99999
    99999
    99999
        Leukocytes;disc/prog;n=1,2,7,3,4,1
    0
    1
    2
    3
    3
    1
    Notes
    [149] - All Treated Population
    [150] - All Treated Population
    [151] - All Treated Population
    [152] - All Treated Population
    [153] - All Treated Population
    [154] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with maximum urinalysis change from Baseline-Besylate sub-study

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    End point title
    Number of participants with maximum urinalysis change from Baseline-Besylate sub-study [155] [156]
    End point description
    Urine samples were collected for the analysis of following urine parameters: pH, glucose, protein, occult blood, ketones, specific gravity, erythrocytes and leukocytes. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Only parameters and time points with non-zero values for any increase have been presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1), Weeks 5,9,17,25 and disc/prog
    Notes
    [155] - 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 statistical analysis was performed
    [156] - 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: The end point is specific for Part 1 QD dosing
    End point values
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Number of subjects analysed
    5 [157]
    5 [158]
    Units: Participants
        Hyaline casts; Week5;n=1,1
    1
    1
        Hyaline casts; Week9;n=2,1
    1
    0
        Hyaline casts; Week17;n=1,0
    1
    99999
        Hyaline casts; Week25;n=1,0
    1
    99999
        Glucose; Week9;n=4,1
    1
    0
        Glucose; Week17;n=2,0
    1
    99999
        Ketones; Week9;n=4,1
    1
    0
        pH;Week5;n=3,2
    3
    1
        pH;Week9;n=4,1
    3
    0
        pH;Week17;n=2,0
    2
    99999
        pH;Week25;n=1,0
    1
    99999
        pH;disc/prog;n=2,2
    2
    1
        Protein; Week5; n=3,2
    3
    1
        Protein; Week9; n=4,1
    3
    1
        Protein; Week17; n=2,0
    2
    99999
        Protein; Week25; n=1,0
    1
    99999
        Erythrocytes; Week9; n=4,1
    2
    1
        Erythrocytes; Week17; n=2,0
    1
    99999
        Erythrocytes; Week25; n=1,0
    1
    99999
        Erythrocytes; disc/prog; n=1,0
    1
    99999
        Specific gravity; Week5; n=3,2
    1
    1
        Specific gravity; Week9; n=4,1
    2
    0
        Specific gravity; Week17; n=2,0
    1
    99999
        Specific gravity; Week25; n=1,0
    1
    99999
        Specific gravity; disc/prog; n=2,2
    0
    1
        Leukocytes; Week5; n=3,1
    3
    1
        Leukocytes; Week9; n=4,1
    4
    1
        Leukocytes; Week17; n=2,0
    1
    99999
        Leukocytes; Week25; n=1,0
    1
    99999
        Leukocytes; disc/prog; n=1,0
    1
    99999
        Glucose; Week 5; n=3,2
    1
    1
    Notes
    [157] - All treated Population
    [158] - All treated Population
    No statistical analyses for this end point

    Primary: Number of participants with changes in pulse rate from Baseline-Part 1 QD

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    End point title
    Number of participants with changes in pulse rate from Baseline-Part 1 QD [159] [160]
    End point description
    Pulse rate was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for pulse rate is <60 beats per minute and >100 beats per minute. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Only those participants with data available at Baseline and the specified time point were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.38 months of drug exposure
    Notes
    [159] - 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 statistical analysis was performed
    [160] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [161]
    4 [162]
    1 [163]
    3 [164]
    4 [165]
    8 [166]
    31 [167]
    9 [168]
    Units: Participants
        Pulse rate; decrease to <60
    0
    1
    0
    1
    0
    1
    1
    1
        Pulse rate; Change to normal/no change
    2
    1
    0
    1
    1
    5
    12
    4
        Pulse rate; increase to >100
    1
    2
    1
    1
    3
    2
    18
    5
    Notes
    [161] - All Treated Population
    [162] - All Treated Population
    [163] - All Treated Population
    [164] - All Treated Population
    [165] - All Treated Population
    [166] - All Treated Population
    [167] - All Treated Population
    [168] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with changes in pulse rate from Baseline-Part 1 BID

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    End point title
    Number of participants with changes in pulse rate from Baseline-Part 1 BID [169] [170]
    End point description
    Pulse rate was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.41 months of drug exposure
    Notes
    [169] - 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 statistical analysis was performed
    [170] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [171]
    10 [172]
    5 [173]
    Units: Participants
        Pulse rate; decrease to <60
    0
    0
    0
        Pulse rate; Change to normal/no change
    3
    4
    2
        Pulse rate; increase to >100
    1
    6
    3
    Notes
    [171] - All Treated Population
    [172] - All Treated Population
    [173] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with changes in pulse rate from Baseline-Part 2

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    End point title
    Number of participants with changes in pulse rate from Baseline-Part 2 [174]
    End point description
    Pulse rate was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for pulse rate is <60 beats per minute and >100 beats per minute. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Participants were counted twice if the participant "Decreased to <60" and "Increased to >100" post-baseline. Only those participants with data available at Baseline and the specified time point were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.41 months of drug exposure
    Notes
    [174] - 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 statistical analysis was performed
    End point values
    Participants with SCLC Participants with TNBC Participants with NMC Participants with CRPC Participants with ER+BC Participants with GIST
    Number of subjects analysed
    14 [175]
    19 [176]
    11 [177]
    22 [178]
    20 [179]
    12 [180]
    Units: Participants
        Pulse rate; decrease to <60
    1
    0
    0
    0
    1
    1
        Pulse rate; Change to normal/no change
    10
    11
    7
    13
    9
    8
        Pulse rate; increase to >100
    4
    9
    5
    9
    10
    3
    Notes
    [175] - All Treated Population
    [176] - All Treated Population
    [177] - All Treated Population
    [178] - All Treated Population
    [179] - All Treated Population
    [180] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with changes in pulse rate from Baseline-Besylate sub-study

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    End point title
    Number of participants with changes in pulse rate from Baseline-Besylate sub-study [181] [182]
    End point description
    Pulse rate was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for pulse rate is <60 beats per minute and >100 beats per minute. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.87 months of drug exposure
    Notes
    [181] - 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 statistical analysis was performed
    [182] - 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: The end point is specific for Part 1 QD dosing
    End point values
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Number of subjects analysed
    5 [183]
    5 [184]
    Units: Participants
        Pulse rate; decrease to <60
    0
    0
        Pulse rate; Change to normal/no change
    3
    1
        Pulse rate; increase to >100
    2
    4
    Notes
    [183] - All treated Population
    [184] - All treated Population
    No statistical analyses for this end point

    Primary: Number of participants with increase in blood pressure from Baseline-Part 1 QD

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    End point title
    Number of participants with increase in blood pressure from Baseline-Part 1 QD [185] [186]
    End point description
    Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. Grading of SBP and DBP were done using NCI-CTCAE version 4.0 where, SBP (millimeters of mercury): Grade 0 (<120), Grade 1 (120-139), Grade 2 (140-159), Grade 3/4 (>=160) and DBP: Grade 0 (<80), Grade 1 (80-89), Grade 2 (90-99), Grade 3/4 (>=100). An increase is defined as an increase in CTCAE grade relative to baseline grade. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.38 months of drug exposure
    Notes
    [185] - 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 statistical analysis was performed
    [186] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [187]
    4 [188]
    1 [189]
    3 [190]
    4 [191]
    9 [192]
    32 [193]
    9 [194]
    Units: Participants
        DBP; Increase to Grade 1
    2
    1
    0
    0
    0
    3
    9
    0
        DBP; Increase to Grade 2
    0
    0
    1
    1
    1
    0
    10
    1
        DBP; Increase to Grade 3/4
    0
    0
    0
    0
    0
    1
    2
    2
        SBP; Increase to Grade 1
    1
    1
    1
    1
    1
    2
    11
    1
        SBP; Increase to Grade 2
    1
    0
    0
    1
    3
    1
    9
    3
        SBP; Increase to Grade 3/4
    0
    1
    0
    0
    0
    2
    5
    2
    Notes
    [187] - All Treated Population
    [188] - All Treated Population
    [189] - All Treated Population
    [190] - All Treated Population
    [191] - All Treated Population
    [192] - All Treated Population
    [193] - All Treated Population
    [194] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with increase in blood pressure from Baseline-Part 1 BID

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    End point title
    Number of participants with increase in blood pressure from Baseline-Part 1 BID [195] [196]
    End point description
    SBP and DBP were measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. Grading of SBP and DBP were done using NCI-CTCAE version 4.0 where, SBP (millimeters of mercury): Grade 0 (<120), Grade 1 (120-139), Grade 2 (140-159), Grade 3/4 (>=160) and DBP: Grade 0 (<80), Grade 1 (80-89), Grade 2 (90-99), Grade 3/4 (>=100). An increase is defined as an increase in CTCAE grade relative to baseline grade. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Only those participants with data available at Baseline and the specified time point were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.41 months of drug exposure
    Notes
    [195] - 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 statistical analysis was performed
    [196] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [197]
    10 [198]
    5 [199]
    Units: Participants
        DBP; Increase to Grade 1;n=4,10,4
    2
    4
    1
        DBP; Increase to Grade 2;n=4,10,4
    0
    4
    1
        DBP; Increase to Grade 3/4;n=4,10,4
    0
    0
    1
        SBP; Increase to Grade 1;n=4,9,5
    1
    2
    2
        SBP; Increase to Grade 2;n=4,9,5
    1
    6
    1
        SBP; Increase to Grade 3/4;n=4,9,5
    0
    0
    1
    Notes
    [197] - All Treated Population
    [198] - All Treated Population
    [199] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with changes in blood pressure from Baseline-Part 2

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    End point title
    Number of participants with changes in blood pressure from Baseline-Part 2 [200]
    End point description
    SBP and DBP were measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. Grading of SBP and DBP were done using NCI-CTCAE version 4.0 where, SBP (millimeters of mercury): Grade 0 (<120), Grade 1 (120-139), Grade 2 (140-159), Grade 3/4 (>=160) and DBP: Grade 0 (<80), Grade 1 (80-89), Grade 2 (90-99), Grade 3/4 (>=100). An increase is defined as an increase in CTCAE grade relative to baseline grade. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Only those participants with data available at Baseline and the specified time point were analyzed (indicated by n=X in category titles).
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.41 months of drug exposure
    Notes
    [200] - 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 statistical analysis was performed
    End point values
    Participants with SCLC Participants with TNBC Participants with NMC Participants with CRPC Participants with GIST Participants with ER+BC
    Number of subjects analysed
    14 [201]
    19 [202]
    11 [203]
    22 [204]
    12 [205]
    19 [206]
    Units: Participants
        DBP; Increase to Grade 1;n=11,14,22,19,19,12
    3
    5
    2
    8
    3
    4
        DBP; Increase to Grade 2;n=11,14,22,19,19,12
    1
    3
    4
    4
    1
    6
        DBP; Increase to Grade 3/4;n=11,14,22,19,19,12
    0
    2
    0
    1
    2
    1
        SBP; Increase to Grade 1;n=11,14,21,19,19,12
    4
    9
    4
    2
    1
    7
        SBP; Increase to Grade 2;n=11,14,21,19,19,12
    4
    3
    2
    11
    7
    4
        SBP; Increase to Grade 3/4;n=11,14,21,19,19,12
    1
    1
    0
    3
    0
    1
    Notes
    [201] - All Treated Population
    [202] - All Treated Population
    [203] - All Treated Population
    [204] - All Treated Population
    [205] - All Treated Population
    [206] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with increase in blood pressure from Baseline-Besylate sub-study

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    End point title
    Number of participants with increase in blood pressure from Baseline-Besylate sub-study [207] [208]
    End point description
    SBP and DBP were measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. Grading of SBP and DBP were done using NCI-CTCAE version 4.0 where, SBP (millimeters of mercury): Grade 0 (<120), Grade 1 (120-139), Grade 2 (140-159), Grade 3/4 (>=160) and DBP: Grade 0 (<80), Grade 1 (80-89), Grade 2 (90-99), Grade 3/4 (>=100). An increase is defined as an increase in CTCAE grade relative to baseline grade. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.87 months of drug exposure
    Notes
    [207] - 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 statistical analysis was performed
    [208] - 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: The end point is specific for Part 1 QD dosing
    End point values
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Number of subjects analysed
    5 [209]
    5 [210]
    Units: Participants
        DBP; Increase to Grade 1
    1
    1
        DBP; Increase to Grade 2
    2
    1
        DBP; Increase to Grade 3/4
    0
    0
        SBP; Increase to Grade 1
    1
    1
        SBP; Increase to Grade 2
    0
    1
        SBP; Increase to Grade 3/4
    0
    0
    Notes
    [209] - All treated Population
    [210] - All treated Population
    No statistical analyses for this end point

    Primary: Number of participants with changes in temperature from Baseline-Part 1 QD

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    End point title
    Number of participants with changes in temperature from Baseline-Part 1 QD [211] [212]
    End point description
    Temperature was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for temperature is <=35 degree Celsius and >=38 degree Celsius. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.38 months of drug exposure
    Notes
    [211] - 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 statistical analysis was performed
    [212] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [213]
    4 [214]
    1 [215]
    3 [216]
    4 [217]
    9 [218]
    32 [219]
    9 [220]
    Units: Participants
        Decrease to <=35
    0
    0
    0
    0
    0
    0
    2
    1
        Change to normal/No change
    3
    3
    1
    3
    3
    9
    27
    8
        Increase to >=38
    0
    1
    0
    0
    1
    0
    3
    0
    Notes
    [213] - All Treated Population
    [214] - All Treated Population
    [215] - All Treated Population
    [216] - All Treated Population
    [217] - All Treated Population
    [218] - All Treated Population
    [219] - All Treated Population
    [220] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with changes in temperature from Baseline-Part 1 BID

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    End point title
    Number of participants with changes in temperature from Baseline-Part 1 BID [221] [222]
    End point description
    Temperature was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for temperature is <=35 degree Celsius and >=38 degree Celsius. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.41 months of drug exposure
    Notes
    [221] - 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 statistical analysis was performed
    [222] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [223]
    10 [224]
    5 [225]
    Units: Participants
        Decrease to <=35
    0
    0
    0
        Change to normal/No change
    4
    9
    5
        Increase to >=38
    0
    1
    0
    Notes
    [223] - All Treated Population
    [224] - All Treated Population
    [225] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with changes in temperature from Baseline-Part 2

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    End point title
    Number of participants with changes in temperature from Baseline-Part 2 [226]
    End point description
    Temperature was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for temperature is <=35 degree Celsius and >=38 degree Celsius. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented. Only those participants with data available at Baseline and the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.41 months of drug exposure
    Notes
    [226] - 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 statistical analysis was performed
    End point values
    Participants with SCLC Participants with TNBC Participants with NMC Participants with CRPC Participants with ER+BC Participants with GIST
    Number of subjects analysed
    14 [227]
    19 [228]
    11 [229]
    22 [230]
    20 [231]
    12 [232]
    Units: Participants
        Decrease to <=35
    0
    0
    1
    0
    1
    0
        Change to normal/No change
    11
    18
    10
    20
    18
    12
        Increase to >=38
    3
    1
    0
    2
    1
    0
    Notes
    [227] - All Treated Population
    [228] - All Treated Population
    [229] - All Treated Population
    [230] - All Treated Population
    [231] - All Treated Population
    [232] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with changes in temperature from Baseline-Besylate sub-study

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    End point title
    Number of participants with changes in temperature from Baseline-Besylate sub-study [233] [234]
    End point description
    Temperature was measured in a supine or semi-recumbent position after at least 5 minutes rest for the participant. The clinical concern range for temperature is <=35 degree Celsius and >=38 degree Celsius. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Data for worst case post-Baseline is presented.
    End point type
    Primary
    End point timeframe
    Baseline (pre-dose Week1 Day1) and median of 1.87 months of drug exposure
    Notes
    [233] - 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 statistical analysis was performed
    [234] - 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: The end point is specific for Part 1 QD dosing
    End point values
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Number of subjects analysed
    5 [235]
    5 [236]
    Units: Participants
        Decrease to <=35
    0
    0
        Change to normal/No change
    4
    5
        Increase to >=38
    1
    0
    Notes
    [235] - All treated Population
    [236] - All treated Population
    No statistical analyses for this end point

    Primary: Overall response rate-Part 1 QD

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    End point title
    Overall response rate-Part 1 QD [237] [238]
    End point description
    Overall response rate is defined as the percentage of participants who achieved a confirmed complete response (CR) or partial response (PR) from the start of treatment until disease progression or the start of new anticancer therapy, among participants who received at least 1 dose of treatment. Overall response rate was determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST version (v) 1.1). CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
    End point type
    Primary
    End point timeframe
    Median of 1.38 months of drug exposure
    Notes
    [237] - 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 statistical analysis was performed
    [238] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [239]
    4 [240]
    1 [241]
    3 [242]
    4 [243]
    9 [244]
    32 [245]
    9 [246]
    Units: Percentage of participants
        number (confidence interval 95%)
    0 (0.0 to 70.8)
    25 (0.6 to 80.6)
    0 (0.0 to 97.5)
    0 (0.0 to 70.8)
    0 (0.0 to 60.2)
    0 (0.0 to 33.6)
    3 (0.1 to 16.2)
    11 (0.3 to 48.2)
    Notes
    [239] - All Treated Population
    [240] - All Treated Population
    [241] - All Treated Population
    [242] - All Treated Population
    [243] - All Treated Population
    [244] - All Treated Population
    [245] - All Treated Population
    [246] - All Treated Population
    No statistical analyses for this end point

    Primary: Overall response rate-Part 1 BID

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    End point title
    Overall response rate-Part 1 BID [247] [248]
    End point description
    Overall response rate is defined as the percentage of participants who achieved a confirmed CR or PR from the start of treatment until disease progression or the start of new anticancer therapy, among participants who received at least 1 dose of treatment. Overall response rate was determined by the investigator according to RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
    End point type
    Primary
    End point timeframe
    Median of 1.41 months of drug exposure
    Notes
    [247] - 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 statistical analysis was performed
    [248] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [249]
    10 [250]
    5 [251]
    Units: Percentage of participants
        number (confidence interval 95%)
    0 (0.0 to 60.2)
    0 (0.0 to 30.8)
    0 (0.0 to 52.2)
    Notes
    [249] - All Treated Population
    [250] - All Treated Population
    [251] - All Treated Population
    No statistical analyses for this end point

    Primary: Overall response rate-Part 2

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    End point title
    Overall response rate-Part 2 [252]
    End point description
    Overall response rate is defined as the percentage of participants who achieved a confirmed CR or PR from the start of treatment until disease progression or the start of new anticancer therapy, among participants who received at least 1 dose of treatment. Overall response rate was determined by the investigator according to RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
    End point type
    Primary
    End point timeframe
    Median of 1.41 months of drug exposure
    Notes
    [252] - 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 statistical analysis was performed
    End point values
    Participants with NMC Participants with SCLC Participants with CRPC Participants with TNBC Participants with ER+BC Participants with GIST
    Number of subjects analysed
    12 [253]
    14 [254]
    23 [255]
    19 [256]
    21 [257]
    13 [258]
    Units: Percentage of participants
        number (confidence interval 95%)
    8 (0.2 to 38.5)
    0 (0.0 to 23.2)
    4 (0.1 to 21.9)
    0 (0.0 to 17.6)
    0 (0.0 to 16.1)
    0 (0.0 to 24.7)
    Notes
    [253] - All Treated Population
    [254] - All Treated Population
    [255] - All Treated Population
    [256] - All Treated Population
    [257] - All Treated Population
    [258] - All Treated Population
    No statistical analyses for this end point

    Primary: Overall response rate-Besylate sub-study

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    End point title
    Overall response rate-Besylate sub-study [259]
    End point description
    Overall response rate is defined as the percentage of participants who achieved a confirmed CR or PR from the start of treatment until disease progression or the start of new anticancer therapy, among participants who received at least 1 dose of treatment. Overall response rate was determined by the investigator according to RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Data for Besylate sub-study participants were combined for analysis to provide useful interpretation of study data as pre-specified in RAP.
    End point type
    Primary
    End point timeframe
    Median of 1.87 months of drug exposure
    Notes
    [259] - 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 statistical analysis was performed
    End point values
    All participants in Besylate sub-study
    Number of subjects analysed
    10 [260]
    Units: Percentage of participants
        number (confidence interval 95%)
    0 (0.0 to 30.8)
    Notes
    [260] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with prostate specific antigen (PSA)50 response-Part 1 QD

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    End point title
    Number of participants with prostate specific antigen (PSA)50 response-Part 1 QD [261] [262]
    End point description
    PSA 50 response rate is defined as the response rate that a PSA reduction from Baseline >=50% is observed at 12 weeks and beyond (must be confirmed by a second value). The number of participants with PSA >=50% reduction is presented along with 95% confidence intervals. 99999 indicates confidence interval could not be calculated as there were no responders.
    End point type
    Primary
    End point timeframe
    Median of 1.38 months of drug exposure
    Notes
    [261] - 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 statistical analysis was performed
    [262] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part1: GSK525762 2 mg QD Part1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Part 1: GSK525762 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD
    Number of subjects analysed
    3 [263]
    4 [264]
    1 [265]
    3 [266]
    4 [267]
    9 [268]
    32 [269]
    9 [270]
    Units: Participants
        number (confidence interval 95%)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [263] - All Treated Population
    [264] - All Treated Population
    [265] - All Treated Population
    [266] - All Treated Population
    [267] - All Treated Population
    [268] - All Treated Population
    [269] - All Treated Population
    [270] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with PSA50 response rate-Part 1 BID

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    End point title
    Number of participants with PSA50 response rate-Part 1 BID [271] [272]
    End point description
    PSA 50 Response rate is defined as the response rate that a PSA reduction from Baseline >=50% is observed at 12 weeks and beyond (must be confirmed by a second value). The number of participants with PSA >=50% reduction is presented along with 95% confidence intervals. 99999 indicates confidence interval could not be calculated as there were no responders.
    End point type
    Primary
    End point timeframe
    Median of 1.41 months of drug exposure
    Notes
    [271] - 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 statistical analysis was performed
    [272] - 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: The end point is specific for Part 1 QD dosing
    End point values
    Part 1: GSK525762 20 mg BID Part 1: GSK525762 30 mg BID Part 1: GSK525762 40 mg BID
    Number of subjects analysed
    4 [273]
    10 [274]
    5 [275]
    Units: Participants
        number (confidence interval 95%)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [273] - All Treated Population
    [274] - All Treated Population
    [275] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with PSA50 response-Part 2

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    End point title
    Number of participants with PSA50 response-Part 2 [276]
    End point description
    PSA 50 response rate is defined as the response rate that a PSA reduction from Baseline >=50% is observed at 12 weeks and beyond (must be confirmed by a second value). The number of participants with PSA >=50% reduction is presented along with 95% confidence intervals. 99999 indicates confidence interval could not be calculated as there were no responders.
    End point type
    Primary
    End point timeframe
    Median of 1.41 months of drug exposure
    Notes
    [276] - 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 statistical analysis was performed
    End point values
    Participants with NMC Participants with SCLC Participants with CRPC Participants with TNBC Participants with ER+BC Participants with GIST
    Number of subjects analysed
    12 [277]
    14 [278]
    23 [279]
    19 [280]
    21 [281]
    13 [282]
    Units: Participants
        number (confidence interval 95%)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [277] - All Treated Population
    [278] - All Treated Population
    [279] - All Treated Population
    [280] - All Treated Population
    [281] - All Treated Population
    [282] - All Treated Population
    No statistical analyses for this end point

    Primary: Number of participants with PSA50 response-Besylate sub-study

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    End point title
    Number of participants with PSA50 response-Besylate sub-study [283] [284]
    End point description
    PSA 50 Response rate is defined as the response rate that a PSA reduction from Baseline >=50% is observed at 12 weeks and beyond (must be confirmed by a second value). The number of participants with PSA >=50% reduction is presented along with 95% confidence intervals.
    End point type
    Primary
    End point timeframe
    Median of 1.87 months of drug exposure
    Notes
    [283] - 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 statistical analysis was performed
    [284] - 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: The end point is specific for Part 1 QD dosing
    End point values
    80mg Amor+6mg Iso/80mg Bes+6mg Iso/30mg Bes+6mg Iso/80mg Bes 80mg Bes+6mg Iso/80mg Amor+6mg Iso/30mg Bes+6mg Iso/80mg Bes
    Number of subjects analysed
    5 [285]
    5 [286]
    Units: Participants
        number (confidence interval 95%)
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [285] - All treated Population
    [286] - All treated Population
    No statistical analyses for this end point

    Primary: Area under the concentration-time curve (AUC) from time zero to 24 hours(AUC[0 to 24]); AUC from time 0 to last quantifiable concentration (AUC [0 to t]) and AUC extrapolated to infinity (AUC[0 to inf]) of GSK525762-Besylate sub-study

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    End point title
    Area under the concentration-time curve (AUC) from time zero to 24 hours(AUC[0 to 24]); AUC from time 0 to last quantifiable concentration (AUC [0 to t]) and AUC extrapolated to infinity (AUC[0 to inf]) of GSK525762-Besylate sub-study [287]
    End point description
    Blood samples for pharmacokinetic analysis of GSK525762 were collected at the indicated time points. Besylate sub-study pharmacokinetic (PK) Parameter Population consisted of all participants in the PK Parameter Population who participated in the besylate substudy. Only those participants with data available at the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Week1 Day1, Day3 and Week2 Day1 (pre-dose,0.25,0.5,1,1.5,2,3,4,6,8,24,48 hours post-dose)
    Notes
    [287] - 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 statistical analysis was performed
    End point values
    GSK525762 80 mg amorphous+6 mg stable isotope GSK525762 80 mg besylate+6 mg stable isotope GSK525762 30 mg besylate+6 mg stable isotope GSK525762 80 mg besylate fed
    Number of subjects analysed
    9 [288]
    10 [289]
    10 [290]
    8 [291]
    Units: Hours*nanograms per milliliter
    geometric mean (geometric coefficient of variation)
        AUC(0 to 24)
    6954.3 ± 59.1
    7377.9 ± 44.7
    2977.3 ± 42.8
    9123.8 ± 45.2
        AUC(0 to inf)
    7292.0 ± 62.1
    7703.4 ± 49.9
    3096.9 ± 45.0
    9727.7 ± 48.5
        AUC(0 to t)
    7227.1 ± 61.6
    7657.6 ± 49.9
    3053.9 ± 44.4
    9597.1 ± 48.9
    Notes
    [288] - Besylate Sub-Study PK Parameter Population
    [289] - Besylate Sub-Study PK Parameter Population
    [290] - Besylate Sub-Study PK Parameter Population
    [291] - Besylate Sub-Study PK Parameter Population
    No statistical analyses for this end point

    Primary: Maximum observed concentration (Cmax) of GSK525762-Besylate sub-study

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    End point title
    Maximum observed concentration (Cmax) of GSK525762-Besylate sub-study [292]
    End point description
    Blood samples for pharmacokinetic analysis of GSK525762 were collected at the indicated time points. Only those participants with data available at the specified time points were analyzed.
    End point type
    Primary
    End point timeframe
    Week1 Day1, Day3 and Week2 Day1 (pre-dose,0.25,0.5,1,1.5,2,3,4,6,8,24,48 hours post-dose)
    Notes
    [292] - 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 statistical analysis was performed
    End point values
    GSK525762 80 mg amorphous+6 mg stable isotope GSK525762 80 mg besylate+6 mg stable isotope GSK525762 30 mg besylate+6 mg stable isotope GSK525762 80 mg besylate fed
    Number of subjects analysed
    9 [293]
    10 [294]
    10 [295]
    8 [296]
    Units: Nanograms per milliliter
        geometric mean (geometric coefficient of variation)
    1431.41 ± 51.3
    1483.21 ± 49.8
    655.33 ± 21.1
    1305.59 ± 46.6
    Notes
    [293] - Besylate Sub-Study PK Parameter Population
    [294] - Besylate Sub-Study PK Parameter Population
    [295] - Besylate Sub-Study PK Parameter Population
    [296] - Besylate Sub-Study PK Parameter Population
    No statistical analyses for this end point

    Primary: Apparent terminal phase elimination rate constant (lambda z) for GSK525762-Besylate sub-study

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    End point title
    Apparent terminal phase elimination rate constant (lambda z) for GSK525762-Besylate sub-study [297]
    End point description
    Blood samples for pharmacokinetic analysis of GSK525762 were collected at the indicated time points. Only those participants with data available at the specified time points were analyzed.
    End point type</