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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 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

Trial information Top of page

Subject disposition Top of page
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      Adverse event, serious fatal 2 4 1 3 4 7 30 7 1 9 3 8 12 21 16 17 5 5 4      Physician decision 1 - - - - - - - - - - 1 - - - - - - -      Consent withdrawn by subject - - - - - - - - 1 - 1 - - - - 1 - - 1      Site closed - - - - - - 2 - - 1 1 2 2 1 1 3 8 - -      Lost to follow-up - - - - - 1 - 2 1 - - 1 - - 2 - - - -

Subject disposition Top of page

Baseline characteristics Top of page
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

Baseline characteristics Top of page

End points Top of page
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.

End points Top of page

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

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

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

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

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

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

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

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

Primary: Number of participants withdrawn due to toxicities-Part 1 QD Top of page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

Primary: Number of participants withdrawn due to toxicities-Part 1 BID Top of page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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Primary: Overall response rate-Part 1 QD Top of page
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 QD Top of page

Primary: Overall response rate-Part 1 BID Top of page
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 1 BID Top of page

Primary: Overall response rate-Part 2 Top of page
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-Part 2 Top of page

Primary: Overall response rate-Besylate sub-study Top of page
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: Overall response rate-Besylate sub-study Top of page

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

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

Primary: Number of participants with PSA50 response-Part 2 Top of page
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-Part 2 Top of page

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

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 Top of page
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: 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 Top of page

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

Primary: Apparent terminal phase elimination rate constant (lambda z) for GSK525762-Besylate sub-study Top of page
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	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 [297] - 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 [298] 10 [299] 10 [300] 8 [301] Units: Per hour     geometric mean (geometric coefficient of variation) 5.628 ± 25.9 5.176 ± 20.6 5.088 ± 23.8 5.954 ± 20.2
Notes [298] - Besylate Sub-Study PK Parameter Population [299] - Besylate Sub-Study PK Parameter Population [300] - Besylate Sub-Study PK Parameter Population [301] - 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 Top of page

Primary: Time to reach Cmax (Tmax) for GSK525762-Besylate sub-study Top of page
End point title	Time to reach Cmax (Tmax) for GSK525762-Besylate sub-study [302]
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 [302] - 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 [303] 10 [304] 10 [305] 8 [306] Units: Hours     median (full range (min-max)) 0.5833 (0.250 to 3.250) 0.8083 (0.500 to 3.000) 0.8333 (0.300 to 1.017) 2.0000 (0.500 to 6.050)
Notes [303] - Besylate Sub-Study PK Parameter Population [304] - Besylate Sub-Study PK Parameter Population [305] - Besylate Sub-Study PK Parameter Population [306] - Besylate Sub-Study PK Parameter Population
No statistical analyses for this end point

Primary: Time to reach Cmax (Tmax) for GSK525762-Besylate sub-study Top of page

Secondary: Number of participants with increase in QT interval corrected for heart rate according to Fridericia’s formula (QTcF)-Part 1 QD Top of page
End point title	Number of participants with increase in QT interval corrected for heart rate according to Fridericia’s formula (QTcF)-Part 1 QD [307]
End point description	Electrocardiogram (ECG) measurements were done using an automated 12-lead ECG machine. QTc parameters were graded according to NCI-CTCAE version 4.0. Grade 0 (<450 milliseconds [msec]), Grade 1 (450-480 msec), Grade 2 (481-500 msec), Grade 3 (>=501 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Number of participants with increase in QTcF at worst-case post Baseline is reported. Low doses (GSK525762 2-16 mg QD) were combined to better interpret study data as there were small numbers of participants within a single low dose level.
End point type	Secondary
End point timeframe	Median of 1.38 months of drug exposure
Notes [307] - 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 4 1 3 4 9 32 9 Units: Participants     Any Grade increase 1 0 0 1 4 4 13 4     Increase to Grade 2 0 0 0 0 0 1 0 1     Increase to Grade 3 1 0 0 0 0 0 0 0
No statistical analyses for this end point

Secondary: Number of participants with increase in QT interval corrected for heart rate according to Fridericia’s formula (QTcF)-Part 1 QD Top of page

Secondary: Number of participants with increase in QTcF-Part 1 BID Top of page
End point title	Number of participants with increase in QTcF-Part 1 BID [308]
End point description	ECG measurements were done using an automated 12-lead ECG machine. QTc parameters were graded according to NCI-CTCAE version 4.0. Grade 0 (<450 milliseconds [msec]), Grade 1 (450-480 msec), Grade 2 (481-500 msec), Grade 3 (>=501 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Number of participants with increase in QTcF at worst-case post Baseline is reported.
End point type	Secondary
End point timeframe	Median of 1.41 months of drug exposure
Notes [308] - 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 10 5 Units: Participants     Any Grade increase 3 4 2     Increase to Grade 2 3 0 0     Increase to Grade 3 0 0 0
No statistical analyses for this end point

Secondary: Number of participants with increase in QTcF-Part 1 BID Top of page

Secondary: Number of participants with increase in QTcF-Part 2 Top of page
End point title	Number of participants with increase in QTcF-Part 2
End point description	ECG measurements were done using an automated 12-lead ECG machine. QTc parameters were graded according to NCI-CTCAE version 4.0. Grade 0 (<450 milliseconds [msec]), Grade 1 (450-480 msec), Grade 2 (481-500 msec), Grade 3 (>=501 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Number of participants with increase in QTcF at worst-case post Baseline is reported. Only those participants with data available at the specified time point were analyzed.
End point type	Secondary
End point timeframe	Median of 1.41 months of drug exposure
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 19 11 22 20 12 Units: Participants     Any Grade increase 2 1 1 6 2 0     Increase to Grade 2 0 0 0 0 2 0     Increase to Grade 3 0 0 1 0 0 0
No statistical analyses for this end point

Secondary: Number of participants with increase in QTcF-Part 2 Top of page

Secondary: Number of participants with increase in QTcF-Besylate sub-study Top of page
End point title	Number of participants with increase in QTcF-Besylate sub-study [309]
End point description	ECG measurements were done using 12-lead ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QTcF intervals. QTc parameters were graded according to NCI-CTCAE version 4.0. Grade 0 (<450 milliseconds [msec]), Grade 1 (450-480 msec), Grade 2 (481-500 msec), Grade 3 (>=501 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Number of participants with increase in QTcF at worst-case post Baseline is reported.
End point type	Secondary
End point timeframe	Median of 1.87 months of drug exposure
Notes [309] - 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 [310] 5 [311] Units: Participants     Any Grade increase 2 0     Increase to Grade 2 0 0     Increase to Grade 3 0 0
Notes [310] - All treated Population [311] - All treated Population
No statistical analyses for this end point

Secondary: Number of participants with increase in QTcF-Besylate sub-study Top of page

Secondary: Progression free survival-Part 1 QD Top of page
End point title	Progression free survival-Part 1 QD [312]
End point description	Progression free survival is defined as the interval of time (in months) between the date of first dose and the earlier of the date of disease progression and date of death due to any cause. Confidence intervals were estimated using Brookmeyer Crowley method. 99999 indicates confidence interval could not be calculated as only one participant was analyzed.
End point type	Secondary
End point timeframe	Median of 1.38 months of drug exposure
Notes [312] - 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 [313] 4 [314] 1 [315] 3 [316] 4 [317] 9 [318] 32 [319] 9 [320] Units: Months     median (confidence interval 95%) 0.3 (0.3 to 0.4) 4.1 (0.9 to 13.9) 2.2 (-99999 to 99999) 9.1 (1.4 to 13.9) 3.8 (0.9 to 5.4) 3.6 (1.4 to 8.9) 6.5 (2.6 to 9.1) 7.5 (6.0 to 18.0)
Notes [313] - All Treated Population [314] - All Treated Population [315] - All Treated Population [316] - All Treated Population [317] - All Treated Population [318] - All Treated Population [319] - All Treated Population [320] - All Treated Population
No statistical analyses for this end point

Secondary: Progression free survival-Part 1 QD Top of page

Secondary: Progression free survival-Part 1 BID Top of page
End point title	Progression free survival-Part 1 BID [321]
End point description	Progression free survival is defined as the interval of time (in months) between the date of first dose and the earlier of the date of disease progression and date of death due to any cause. Confidence intervals were estimated using Brookmeyer Crowley method.
End point type	Secondary
End point timeframe	Median of 1.41 months of drug exposure
Notes [321] - 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 [322] 10 [323] 5 [324] Units: Months     median (confidence interval 95%) 7.7 (0.9 to 14.5) 5.6 (2.9 to 7.0) 8.0 (7.9 to 18.7)
Notes [322] - All Treated Population [323] - All Treated Population [324] - All Treated Population
No statistical analyses for this end point

Secondary: Progression free survival-Part 1 BID Top of page

Secondary: Progression free survival-Part 2 Top of page
End point title	Progression free survival-Part 2
End point description	Progression free survival is defined as the interval of time (in months) between the date of first dose and the earlier of the date of disease progression and the date of death due to any cause. Confidence intervals were estimated using Brookmeyer Crowley method.
End point type	Secondary
End point timeframe	Median of 1.41 months of drug exposure
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 [325] 14 [326] 23 [327] 19 [328] 21 [329] 13 [330] Units: Months     median (confidence interval 95%) 4.8 (2.5 to 5.1) 2.2 (1.1 to 5.3) 8.0 (5.5 to 11.7) 2.4 (1.4 to 6.5) 4.7 (3.3 to 9.2) 3.4 (1.9 to 7.3)
Notes [325] - All Treated Population [326] - All Treated Population [327] - All Treated Population [328] - All Treated Population [329] - All Treated Population [330] - All Treated Population
No statistical analyses for this end point

Secondary: Progression free survival-Part 2 Top of page

Secondary: Progression free survival-Besylate sub-study Top of page
End point title	Progression free survival-Besylate sub-study
End point description	Progression free survival is defined as the interval of time (in months) between the date of first dose and the earlier of the date of disease progression and the date of death due to any cause. Confidence intervals were estimated using Brookmeyer Crowley method. 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	Secondary
End point timeframe	Median of 1.87 months of drug exposure
End point values All participants in Besylate sub-study Number of subjects analysed 10 [331] Units: Months     median (confidence interval 95%) 3.5 (1.0 to 10.9)
Notes [331] - All Treated Population
No statistical analyses for this end point

Secondary: Progression free survival-Besylate sub-study Top of page

Secondary: Time to response-Part 1 QD Top of page
End point title	Time to response-Part 1 QD [332]
End point description	Time to response is defined, for participants with a confirmed CR or PR, as the time from first dose to the first documented evidence of CR or PR. Time to response is not derived for participants with incomplete response dates. Confidence intervals were estimated using Brookmeyer Crowley method. Participants with incomplete response dates were excluded from the analysis.
End point type	Secondary
End point timeframe	Median of 1.38 months of drug exposure
Notes [332] - 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 0 [333] 0 [334] 0 [335] 0 [336] 0 [337] 0 [338] 0 [339] 0 [340] Units: Months     median (confidence interval 95%) ( to ) ( to ) ( to ) ( to ) ( to ) ( to ) ( to ) ( to )
Notes [333] - All Treated Population [334] - All Treated Population [335] - All Treated Population [336] - All Treated Population [337] - All Treated Population [338] - All Treated Population [339] - All Treated Population [340] - All Treated Population
No statistical analyses for this end point

Secondary: Time to response-Part 1 QD Top of page

Secondary: Time to response-Part 1 BID Top of page
End point title	Time to response-Part 1 BID [341]
End point description	Time to response is defined, for participants with a confirmed CR or PR, as the time from first dose to the first documented evidence of CR or PR. Time to response is not derived for participants with incomplete response dates. Confidence intervals were estimated using Brookmeyer Crowley method. Participants with incomplete response dates were excluded from the analysis.
End point type	Secondary
End point timeframe	Median of 1.41 months of drug exposure
Notes [341] - 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 0 [342] 0 [343] 0 [344] Units: Months     median (confidence interval 95%) ( to ) ( to ) ( to )
Notes [342] - All Treated Population [343] - All Treated Population [344] - All Treated Population
No statistical analyses for this end point

Secondary: Time to response-Part 1 BID Top of page

Secondary: Time to response-Part 2 Top of page
End point title	Time to response-Part 2
End point description	Time to response is defined, for participants with a confirmed CR or PR, as the time from first dose to the first documented evidence of CR or PR. Time to response is not derived for participants with incomplete response dates. Confidence intervals were estimated using Brookmeyer Crowley method. Participants with incomplete response dates were excluded from the analysis.
End point type	Secondary
End point timeframe	Median of 1.41 months of drug exposure
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 0 [345] 0 [346] 0 [347] 0 [348] 0 [349] 0 [350] Units: Months     median (confidence interval 95%) ( to ) ( to ) ( to ) ( to ) ( to ) ( to )
Notes [345] - All Treated Population [346] - All Treated Population [347] - All Treated Population [348] - All Treated Population [349] - All Treated Population [350] - All Treated Population
No statistical analyses for this end point

Secondary: Time to response-Part 2 Top of page

Secondary: Time to response-Besylate sub-study Top of page
End point title	Time to response-Besylate sub-study [351]
End point description	Time to response is defined, for participants with a confirmed CR or PR, as the time from first dose to the first documented evidence of CR or PR. Time to response is not derived for participants with incomplete response dates. Confidence intervals were estimated using Brookmeyer Crowley method. Participants with incomplete response dates were excluded from the analysis.
End point type	Secondary
End point timeframe	Median of 1.87 months of drug exposure
Notes [351] - 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 0 [352] 0 [353] Units: Months     median (confidence interval 95%) ( to ) ( to )
Notes [352] - All treated Population [353] - All treated Population
No statistical analyses for this end point

Secondary: Time to response-Besylate sub-study Top of page

Secondary: Duration of response-Part 1 QD Top of page
End point title	Duration of response-Part 1 QD [354]
End point description	Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve a confirmed CR or PR. Duration of response is not derived for participants with incomplete response dates. Confidence intervals were estimated using Brookmeyer Crowley method. Participants with incomplete response dates were excluded from the analysis.
End point type	Secondary
End point timeframe	Median of 1.38 months of drug exposure
Notes [354] - 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 0 [355] 0 [356] 0 [357] 0 [358] 0 [359] 0 [360] 0 [361] 0 [362] Units: Months     median (confidence interval 95%) ( to ) ( to ) ( to ) ( to ) ( to ) ( to ) ( to ) ( to )
Notes [355] - All Treated Population [356] - All Treated Population [357] - All Treated Population [358] - All Treated Population [359] - All Treated Population [360] - All Treated Population [361] - All Treated Population [362] - All Treated Population
No statistical analyses for this end point

Secondary: Duration of response-Part 1 QD Top of page

Secondary: Duration of response-Part 1 BID Top of page
End point title	Duration of response-Part 1 BID [363]
End point description	Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve a confirmed CR or PR. Duration of response is not derived for participants with incomplete response dates. Confidence intervals were estimated using Brookmeyer Crowley method. Participants with incomplete response dates were excluded from the analysis.
End point type	Secondary
End point timeframe	Median of 1.41 months of drug exposure
Notes [363] - 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 0 [364] 0 [365] 0 [366] Units: Months     median (confidence interval 95%) ( to ) ( to ) ( to )
Notes [364] - All Treated Population [365] - All Treated Population [366] - All Treated Population
No statistical analyses for this end point

Secondary: Duration of response-Part 1 BID Top of page

Secondary: Duration of response-Part 2 Top of page
End point title	Duration of response-Part 2
End point description	Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve a confirmed CR or PR. Duration of response is not derived for participants with incomplete response dates. Confidence intervals were estimated using Brookmeyer Crowley method. Participants with incomplete response dates were excluded from the analysis.
End point type	Secondary
End point timeframe	Median of 1.41 months of drug exposure
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 0 [367] 0 [368] 0 [369] 0 [370] 0 [371] 0 [372] Units: Months     median (confidence interval 95%) ( to ) ( to ) ( to ) ( to ) ( to ) ( to )
Notes [367] - All Treated Population [368] - All Treated Population [369] - All Treated Population [370] - All Treated Population [371] - All Treated Population [372] - All Treated Population
No statistical analyses for this end point

Secondary: Duration of response-Part 2 Top of page

Secondary: Duration of response-Besylate sub-study Top of page
End point title	Duration of response-Besylate sub-study [373]
End point description	Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve a confirmed CR or PR. Duration of response is not derived for participants with incomplete response dates. Confidence intervals were estimated using Brookmeyer Crowley method. Participants with incomplete response dates were excluded from the analysis.
End point type	Secondary
End point timeframe	Median of 1.87 months of drug exposure
Notes [373] - 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 0 [374] 0 [375] Units: Months     median (confidence interval 95%) ( to ) ( to )
Notes [374] - All treated Population [375] - All treated Population
No statistical analyses for this end point

Secondary: Duration of response-Besylate sub-study Top of page

Secondary: Overall survival-Part 1 QD Top of page
End point title	Overall survival-Part 1 QD [376]
End point description	Overall survival is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause. The median overall survival is presented along with 95% confidence interval. Confidence intervals were estimated using Brookmeyer Crowley method. 99999 indicates confidence interval could not be calculated as only one participant was analyzed.
End point type	Secondary
End point timeframe	Median of 1.38 months of drug exposure
Notes [376] - 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 [377] 4 [378] 1 [379] 3 [380] 4 [381] 9 [382] 32 [383] 9 [384] Units: Months     median (confidence interval 95%) 0.6 (0.3 to 99999) 4.1 (0.9 to 13.9) 2.2 (-99999 to 99999) 9.1 (5.6 to 13.9) 3.8 (2.8 to 5.4) 8.9 (3.6 to 20.2) 7.1 (3.9 to 9.5) 9.8 (6.0 to 18.0)
Notes [377] - All Treated Population [378] - All Treated Population [379] - All Treated Population [380] - All Treated Population [381] - All Treated Population [382] - All Treated Population [383] - All Treated Population [384] - All Treated Population
No statistical analyses for this end point

Secondary: Overall survival-Part 1 QD Top of page

Secondary: Overall survival-Part 1 BID Top of page
End point title	Overall survival-Part 1 BID [385]
End point description	Overall survival is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause. The median overall survival is presented along with 95% confidence interval. Confidence intervals were estimated using Brookmeyer Crowley method. 99999 indicates values could not be estimated due to limited amount of observed follow-up time.
End point type	Secondary
End point timeframe	Median of 1.41 months of drug exposure
Notes [385] - 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 [386] 10 [387] 5 [388] Units: Months     median (confidence interval 95%) 99999 (14.5 to 99999) 6.0 (2.9 to 12.2) 13.3 (7.9 to 18.7)
Notes [386] - All Treated Population [387] - All Treated Population [388] - All Treated Population
No statistical analyses for this end point

Secondary: Overall survival-Part 1 BID Top of page

Secondary: Overall survival-Part 2 Top of page
End point title	Overall survival-Part 2
End point description	Overall survival is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause. The median overall survival is presented along with 95% confidence interval. Confidence intervals were estimated using Brookmeyer Crowley method. 99999 indicates the upper limit of the 95% CI could not be estimated due to the low number of participants being analyzed.
End point type	Secondary
End point timeframe	Median of 1.41 months of drug exposure
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 [389] 14 [390] 23 [391] 19 [392] 21 [393] 13 [394] Units: Months     median (confidence interval 95%) 5.0 (4.3 to 99999) 2.6 (1.1 to 9.4) 9.1 (6.7 to 11.7) 5.0 (2.3 to 10.3) 8.8 (3.6 to 13.1) 7.3 (3.4 to 99999)
Notes [389] - All Treated Population [390] - All Treated Population [391] - All Treated Population [392] - All Treated Population [393] - All Treated Population [394] - All Treated Population
No statistical analyses for this end point

Secondary: Overall survival-Part 2 Top of page

Secondary: Overall survival-Besylate sub-study Top of page
End point title	Overall survival-Besylate sub-study
End point description	Overall survival is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause. The median overall survival is presented along with 95% confidence interval. Confidence intervals were estimated using Brookmeyer Crowley method. 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	Secondary
End point timeframe	Median of 1.87 months of drug exposure
End point values All participants in Besylate sub-study Number of subjects analysed 10 [395] Units: Months     median (confidence interval 95%) 6.3 (3.6 to 10.9)
Notes [395] - All Treated Population
No statistical analyses for this end point

Secondary: Overall survival-Besylate sub-study Top of page

Secondary: AUC (0 to t), AUC (0 to 24) and AUC (0 to inf) of GSK525762-Part 1 QD Top of page
End point title	AUC (0 to t), AUC (0 to 24) and AUC (0 to inf) of GSK525762-Part 1 QD [396]
End point description	Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK525762. PK parameter population comprised of all participants in the PK Concentration Population (all participants in the All Treated Population for whom a blood sample for pharmacokinetics is obtained and analyzed) for whom a PK parameter has been obtained. Only those participants with data available at the specified time points were available (indicated by n=X in category titles). 99999 indicates geometric coefficient of variation could not be calculated as only one participant was analyzed at the specified time point.
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12,24 and 48 hours post-dose at Week1 Day1 and Week 3 Day 4
Notes [396] - 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 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD Part 1: GSK525762 2 mg QD Part 1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Number of subjects analysed 4 [397] 9 [398] 32 [399] 9 [400] 3 [401] 4 [402] 1 [403] 3 [404] Units: Hours*nanogram per milliliter geometric mean (geometric coefficient of variation)     AUC (0 to 24); Week1;n=3,4,1,3,4,9,32,9 3943.2 ± 49.5 4225.0 ± 39.2 5692.4 ± 61.4 6958.3 ± 43.5 169.2 ± 39.4 354.3 ± 33.8 431.5 ± 99999 867.9 ± 39.5     AUC (0 to 24); Week3;n=1,2,1,3,4,6,16,6 3146.2 ± 54.5 2575.6 ± 47.3 2959.8 ± 48.4 3818.5 ± 35.8 152.9 ± 99999 334.6 ± 60.5 329.5 ± 99999 671.6 ± 21.4     AUC (0 to inf); Week1;n=3,4,1,3,4,9,32,9 4464.5 ± 62.9 4357.5 ± 42.1 5887.2 ± 62.8 7295.6 ± 45.2 174.4 ± 44.3 360.8 ± 35.1 433.1 ± 99999 887.1 ± 39.1     AUC (0 to t); Week1;n=3,4,1,3,4,9,32,9 4147.8 ± 54.3 4304.1 ± 40.7 5667.3 ± 61.5 7218.4 ± 45.1 168.6 ± 44.5 357.5 ± 34.8 431.1 ± 99999 877.7 ± 39.4     AUC (0 to t); Week3;n=1,2,1,3,4,6,16,6 3164.3 ± 54.7 2576.9 ± 47.3 2953.8 ± 49.0 3819.9 ± 35.9 152.8 ± 99999 334.3 ± 60.3 330.6 ± 99999 672.3 ± 21.5
Notes [397] - PK Parameter Population [398] - PK Parameter Population [399] - PK Parameter Population [400] - PK Parameter Population [401] - PK Parameter Population [402] - PK Parameter Population [403] - PK Parameter Population [404] - PK Parameter Population
No statistical analyses for this end point

Secondary: AUC (0 to t), AUC (0 to 24) and AUC (0 to inf) of GSK525762-Part 1 QD Top of page

Secondary: Maximum observed concentration for GSK525762-Part 1 QD Top of page
End point title	Maximum observed concentration for GSK525762-Part 1 QD [405]
End point description	Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates geometric coefficient of variation could not be calculated as only one participant was analyzed at the specified time point.
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12,24 and 48 hours post-dose at Week1 Day1 and Week 3 Day 4
Notes [405] - 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 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD Part 1: GSK525762 2 mg QD Part 1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Number of subjects analysed 4 [406] 9 [407] 32 [408] 9 [409] 3 [410] 4 [411] 1 [412] 3 [413] Units: Nanogram per milliliter geometric mean (geometric coefficient of variation)     Week1;n=3,4,1,3,4,9,32,9 603.92 ± 30.3 889.52 ± 24.5 1099.81 ± 62.7 1080.49 ± 38.8 50.95 ± 41.5 70.46 ± 29.2 120.35 ± 99999 179.45 ± 39.9     Week3;n=1,2,1,3,4,6,16,6 602.70 ± 17.2 633.71 ± 52.6 815.40 ± 41.1 918.56 ± 41.4 52.04 ± 99999 53.37 ± 16.3 103.18 ± 99999 137.57 ± 25.1
Notes [406] - PK Parameter Population [407] - PK Parameter Population [408] - PK Parameter Population [409] - PK Parameter Population [410] - PK Parameter Population [411] - PK Parameter Population [412] - PK Parameter Population [413] - PK Parameter Population
No statistical analyses for this end point

Secondary: Maximum observed concentration for GSK525762-Part 1 QD Top of page

Secondary: Lambda z for GSK525762-Part 1 QD Top of page
End point title	Lambda z for GSK525762-Part 1 QD [414]
End point description	Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates geometric coefficient of variation could not be calculated as only one participant was analyzed at the specified time point.
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12,24 and 48 hours post-dose at Week1 Day1 and Week 3 Day 4
Notes [414] - 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 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD Part 1: GSK525762 2 mg QD Part 1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Number of subjects analysed 4 [415] 9 [416] 32 [417] 9 [418] 3 [419] 4 [420] 1 [421] 3 [422] Units: Per hour geometric mean (geometric coefficient of variation)     Week1;n=3,4,1,3,4,9,32,9 0.07863 ± 53.1 0.12468 ± 28.2 0.15613 ± 34.1 0.10992 ± 16.0 0.21411 ± 98.4 0.13554 ± 37.4 0.23126 ± 99999 0.09903 ± 43.5     Week3;n=1,2,1,3,4,6,16,6 0.12513 ± 12.7 0.17629 ± 26.3 0.16667 ± 30.6 0.17560 ± 21.1 0.15579 ± 99999 0.15472 ± 11.2 0.14087 ± 99999 0.15599 ± 21.7
Notes [415] - PK Parameter Population [416] - PK Parameter Population [417] - PK Parameter Population [418] - PK Parameter Population [419] - PK Parameter Population [420] - PK Parameter Population [421] - PK Parameter Population [422] - PK Parameter Population
No statistical analyses for this end point

Secondary: Lambda z for GSK525762-Part 1 QD Top of page

Secondary: Tmax for GSK525762-Part 1 QD Top of page
End point title	Tmax for GSK525762-Part 1 QD [423]
End point description	Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12,24 and 48 hours post-dose at Week1 Day1 and Week 3 Day 4
Notes [423] - 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 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD Part 1: GSK525762 2 mg QD Part 1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Number of subjects analysed 4 [424] 9 [425] 32 [426] 9 [427] 3 [428] 4 [429] 1 [430] 3 [431] Units: Hours median (full range (min-max))     Week1;n=3,4,1,3,4,9,32,9 2.0083 (0.967 to 2.233) 1.0000 (0.517 to 4.000) 1.0000 (0.250 to 4.000) 1.0000 (0.667 to 3.950) 0.5833 (0.500 to 0.633) 1.2250 (0.500 to 2.000) 1.1000 (1.100 to 1.100) 2.0167 (0.333 to 3.967)     Week3;n=1,2,1,3,4,6,16,6 0.9000 (0.317 to 4.000) 1.0583 (0.500 to 2.033) 0.5667 (0.300 to 4.017) 1.5000 (0.500 to 2.000) 1.0000 (1.000 to 1.000) 2.5083 (1.017 to 4.000) 0.5000 (0.500 to 0.500) 1.0500 (0.767 to 4.000)
Notes [424] - PK Parameter Population [425] - PK Parameter Population [426] - PK Parameter Population [427] - PK Parameter Population [428] - PK Parameter Population [429] - PK Parameter Population [430] - PK Parameter Population [431] - PK Parameter Population
No statistical analyses for this end point

Secondary: Tmax for GSK525762-Part 1 QD Top of page

Secondary: Apparent clearance of GSK525762-Part 1 QD Top of page
End point title	Apparent clearance of GSK525762-Part 1 QD [432]
End point description	Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates geometric coefficient of variation could not be calculated as only one participant was analyzed at the specified time point.
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12,24 and 48 hours post-dose at Week1 Day1 and Week 3 Day 4
Notes [432] - 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 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD Part 1: GSK525762 2 mg QD Part 1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Number of subjects analysed 4 [433] 9 [434] 32 [435] 9 [436] 3 [437] 4 [438] 1 [439] 3 [440] Units: Liter per hour geometric mean (geometric coefficient of variation)     Week1;n=3,4,1,3,4,9,32,9 6.720 ± 62.9 13.769 ± 42.1 13.589 ± 62.8 13.707 ± 45.2 11.467 ± 44.3 11.085 ± 35.1 18.470 ± 99999 18.036 ± 39.1     Week3;n=1,2,1,3,4,6,16,6 9.535 ± 54.5 23.296 ± 47.3 27.029 ± 48.4 26.188 ± 35.8 13.082 ± 99999 11.955 ± 60.5 24.277 ± 99999 23.823 ± 21.4
Notes [433] - PK Parameter Population [434] - PK Parameter Population [435] - PK Parameter Population [436] - PK Parameter Population [437] - PK Parameter Population [438] - PK Parameter Population [439] - PK Parameter Population [440] - PK Parameter Population
No statistical analyses for this end point

Secondary: Apparent clearance of GSK525762-Part 1 QD Top of page

Secondary: Volume of distribution of GSK525762-Part 1 QD Top of page
End point title	Volume of distribution of GSK525762-Part 1 QD [441]
End point description	Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates geometric coefficient of variation could not be calculated as only one participant was analyzed at the specified time point.
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12,24 and 48 hours post-dose at Week1 Day1 and Week 3 Day 4
Notes [441] - 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 30 mg QD Part 1: GSK525762 60 mg QD Part 1: GSK525762 80 mg QD Part 1: GSK525762 100 mg QD Part 1: GSK525762 2 mg QD Part 1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD Number of subjects analysed 4 [442] 9 [443] 32 [444] 9 [445] 3 [446] 4 [447] 1 [448] 3 [449] Units: Liters geometric mean (geometric coefficient of variation)     Week1;n=3,4,1,3,4,9,32,9 85.46 ± 30.3 110.44 ± 23.5 87.03 ± 56.4 124.70 ± 42.6 53.56 ± 65.9 81.79 ± 34.7 79.87 ± 99999 182.13 ± 92.7     Week3;n=1,2,1,3,4,6,16,6 76.20 ± 44.0 132.14 ± 34.7 162.17 ± 40.6 149.14 ± 26.9 83.97 ± 99999 77.27 ± 47.0 172.33 ± 99999 152.72 ± 44.5
Notes [442] - PK Parameter Population [443] - PK Parameter Population [444] - PK Parameter Population [445] - PK Parameter Population [446] - PK Parameter Population [447] - PK Parameter Population [448] - PK Parameter Population [449] - PK Parameter Population
No statistical analyses for this end point

Secondary: Volume of distribution of GSK525762-Part 1 QD Top of page

Secondary: AUC (0 to inf), AUC (0 to 24) and AUC (0 to t) of GSK525762-Part 1 BID Top of page
End point title	AUC (0 to inf), AUC (0 to 24) and AUC (0 to t) of GSK525762-Part 1 BID [450]
End point description	Blood samples were collected at indicated time points post ante-meridiem (AM) and post-meridiem (PM) dose for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles)
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12 hours post-AM dose at Week1Day1 and Week3 Day 4; Week1 Day5(0.5, 3 hours post-AM dose); pre-dose, 0.25,0.5,1,2,4,8,12, 36 hours post-PM dose at Week1Day1 and Week3 Day4
Notes [450] - 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 [451] 10 [452] 5 [453] Units: Hours*nanogram per milliter geometric mean (geometric coefficient of variation)     AUC (0 to 24); Week1 AM dose;n=3,10,5 856.1 ± 123.7 3067.0 ± 43.9 2794.4 ± 31.8     AUC (0 to 24); Week1 PM dose;n=4,7,5 981.4 ± 84.8 3261.1 ± 59.9 2607.6 ± 36.2     AUC (0 to 24); Week3 AM dose;n=3,7,3 1279.0 ± 116.2 2725.3 ± 92.4 1184.6 ± 17.8     AUC (0 to 24); Week3 PM dose;n=3,5,3 1155.8 ± 102.4 1662.1 ± 29.2 1131.6 ± 28.5     AUC (0 to inf); Week1 AM dose;n=3,10,5 860.4 ± 124.4 3118.3 ± 45.3 2825.8 ± 32.8     AUC (0 to t); Week1 AM dose;n=4,10,5 932.2 ± 97.6 2727.2 ± 40.8 2579.0 ± 28.0     AUC (0 to t); Week1 PM dose;n=4,9,5 927.5 ± 82.5 2840.4 ± 43.4 2446.7 ± 34.2     AUC (0 to t); Week3 AM dose;n=3,7,3 1194.6 ± 110.1 2472.4 ± 89.8 1140.9 ± 16.9     AUC (0 to t); Week3 PM dose;n=3,6,3 1053.6 ± 96.6 1490.8 ± 23.3 1073.6 ± 29.2
Notes [451] - PK Parameter Population [452] - PK Parameter Population [453] - PK Parameter Population
No statistical analyses for this end point

Secondary: AUC (0 to inf), AUC (0 to 24) and AUC (0 to t) of GSK525762-Part 1 BID Top of page

Secondary: Maximum observed concentration of GSK525762-Part 1 BID Top of page
End point title	Maximum observed concentration of GSK525762-Part 1 BID [454]
End point description	Blood samples were collected at indicated time points post ante-meridiem (AM) and post-meridiem (PM) dose for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12 hours post-AM dose at Week1Day1 and Week3 Day 4; Week1 Day5(0.5, 3 hours post-AM dose); pre-dose, 0.25,0.5,1,2,4,8,12, 36 hours post-PM dose at Week1Day1 and Week3 Day4
Notes [454] - 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 [455] 10 [456] 5 [457] Units: Nanogram per milliter geometric mean (geometric coefficient of variation)     Week1 AM dose;n=4,10,5 231.68 ± 70.6 628.01 ± 40.0 703.31 ± 34.2     Week1 PM dose;n=4,9,5 166.62 ± 62.0 445.17 ± 27.6 425.76 ± 29.3     Week3 AM dose;n=3,7,3 284.71 ± 87.1 604.38 ± 66.4 419.15 ± 18.1     Week3 PM dose;n=3,6,3 256.08 ± 94.0 263.72 ± 41.3 229.91 ± 34.8
Notes [455] - PK Parameter Population [456] - PK Parameter Population [457] - PK Parameter Population
No statistical analyses for this end point

Secondary: Maximum observed concentration of GSK525762-Part 1 BID Top of page

Secondary: Lambda z for GSK525762-Part 1 BID Top of page
End point title	Lambda z for GSK525762-Part 1 BID [458]
End point description	Blood samples were collected at indicated time points post ante-meridiem (AM) and post-meridiem (PM) dose for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12 hours post-AM dose at Week1Day1 and Week3 Day 4; Week1 Day5(0.5, 3 hours post-AM dose); pre-dose, 0.25,0.5,1,2,4,8,12, 36 hours post-PM dose at Week1Day1 and Week3 Day4
Notes [458] - 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 [459] 10 [460] 5 [461] Units: Per hour geometric mean (geometric coefficient of variation)     Week1 AM dose;n=3,10,5 0.23463 ± 19.4 0.19989 ± 29.6 0.23721 ± 39.4     Week1 PM dose;n=3,7,3 0.21171 ± 23.1 0.14307 ± 36.6 0.18789 ± 25.2     Week3 AM dose;n=3,7,3 0.23565 ± 27.2 0.21751 ± 27.7 0.30868 ± 19.6     Week3 PM dose;n=3,5,3 0.20507 ± 21.5 0.19263 ± 27.7 0.29133 ± 15.8
Notes [459] - PK Parameter Population [460] - PK Parameter Population [461] - PK Parameter Population
No statistical analyses for this end point

Secondary: Lambda z for GSK525762-Part 1 BID Top of page

Secondary: Tmax for GSK525762-Part 1 BID Top of page
End point title	Tmax for GSK525762-Part 1 BID [462]
End point description	Blood samples were collected at indicated time points post ante-meridiem (AM) and post-meridiem (PM) dose for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12 hours post-AM dose at Week1Day1 and Week3 Day 4; Week1 Day5(0.5, 3 hours post-AM dose); pre-dose, 0.25,0.5,1,2,4,8,12, 36 hours post-PM dose at Week1Day1 and Week3 Day4
Notes [462] - 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 [463] 10 [464] 5 [465] Units: Hour median (full range (min-max))     Week1 AM dose;n=4,10,5 1.5500 (0.583 to 4.283) 0.9667 (0.550 to 2.100) 0.5500 (0.517 to 1.033)     Week1 PM dose;n=4,9,5 1.9583 (1.917 to 4.000) 1.9667 (0.967 to 4.167) 1.9833 (1.017 to 7.733)     Week3 AM dose;n=3,7,3 1.1833 (1.167 to 2.067) 1.0667 (0.250 to 2.017) 0.5833 (0.183 to 1.000)     Week3 PM dose;n=3,6,3 1.0000 (0.500 to 2.083) 1.4500 (0.000 to 2.083) 2.0667 (1.900 to 2.067)
Notes [463] - PK Parameter Population [464] - PK Parameter Population [465] - PK Parameter Population
No statistical analyses for this end point

Secondary: Tmax for GSK525762-Part 1 BID Top of page

Secondary: Apparent clearance of GSK525762-Part 1 BID Top of page
End point title	Apparent clearance of GSK525762-Part 1 BID [466]
End point description	Blood samples were collected at indicated time points post ante-meridiem (AM) and post-meridiem (PM) dose for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12 hours post-AM dose at Week1Day1 and Week3 Day 4; Week1 Day5(0.5, 3 hours post-AM dose); pre-dose, 0.25,0.5,1,2,4,8,12, 36 hours post-PM dose at Week1Day1 and Week3 Day4
Notes [466] - 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 [467] 10 [468] 5 [469] Units: Liter per hour geometric mean (geometric coefficient of variation)     Week1 AM dose;n=3,10,5 23.246 ± 124.4 9.621 ± 45.3 14.155 ± 32.8     Week1 PM dose;n=4,7,5 21.745 ± 82.7 11.057 ± 48.1 16.382 ± 34.6     Week3 AM dose;n=3,7,3 16.731 ± 110.1 11.949 ± 86.1 34.623 ± 18.7     Week3 PM dose;n=3,5,3 18.867 ± 96.0 20.133 ± 26.2 37.097 ± 29.4
Notes [467] - PK Parameter Population [468] - PK Parameter Population [469] - PK Parameter Population
No statistical analyses for this end point

Secondary: Apparent clearance of GSK525762-Part 1 BID Top of page

Secondary: Volume of distribution of GSK525762-Part 1 BID Top of page
End point title	Volume of distribution of GSK525762-Part 1 BID [470]
End point description	Blood samples were collected at indicated time points post ante-meridiem (AM) and post-meridiem (PM) dose for pharmacokinetic analysis of GSK525762. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
End point type	Secondary
End point timeframe	pre-dose,0.25,0.5,1,2,4,8,12 hours post-AM dose at Week1Day1 and Week3 Day 4; Week1 Day5(0.5, 3 hours post-AM dose); pre-dose, 0.25,0.5,1,2,4,8,12, 36 hours post-PM dose at Week1Day1 and Week3 Day4
Notes [470] - 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 [471] 10 [472] 5 [473] Units: Liters geometric mean (geometric coefficient of variation)     Week1 AM dose;n=3,10,5 99.07 ± 91.0 48.13 ± 40.8 59.67 ± 35.0     Week1 PM dose;n=3,7,3 116.52 ± 66.0 77.28 ± 16.6 81.11 ± 52.6     Week3 AM dose;n=3,7,3 71.00 ± 72.8 54.94 ± 61.4 112.17 ± 37.6     Week3 PM dose;n=3,5,3 92.00 ± 65.3 104.52 ± 29.5 127.34 ± 41.7
Notes [471] - PK Parameter Population [472] - PK Parameter Population [473] - PK Parameter Population
No statistical analyses for this end point

Secondary: Volume of distribution of GSK525762-Part 1 BID Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Adverse events and serious adverse events were collected for a duration of Median of 1.38 months of drug exposure-Part 1 QD, Median of 1.41 months of drug exposure-Part 1 BID and Part 2 and Median of 1.87 months of drug exposure-Besylate sub-study.
Adverse event reporting additional description	Adverse events were collected in the All Treated Population.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	21.0
Reporting groups
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 30 mg QD
Reporting group description	Participants were administered once daily oral dose of 30 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 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 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 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	Part 1: GSK525762 2 mg QD
Reporting group description	Participants were administered once daily (QD) oral dose of 2 milligrams (mg) GSK525762.
Reporting group title	Part 1: 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	80mg amor+6mg iso/80mg bes+6mg iso/30mg bes+6mg iso/80mg bes
Reporting group description	Participants received GSK525762 80 mg amorphous (amor) free-base 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 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 FDA recommended high fat breakfast in Period 4.
Serious adverse events Part 1: GSK525762 60 mg QD Part 1: GSK525762 30 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 SCLC Part 2: Participants with NMC Part 2: Participants with CRPC Part 2: Participants with TNBC Part 2: Participants with ER+BC Part 2: Participants with GIST Part 1: GSK525762 2 mg QD Part 1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD 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 subjects affected by serious adverse events      subjects affected / exposed 2 / 9 (22.22%) 1 / 4 (25.00%) 21 / 32 (65.63%) 3 / 9 (33.33%) 0 / 4 (0.00%) 4 / 10 (40.00%) 2 / 5 (40.00%) 9 / 14 (64.29%) 6 / 12 (50.00%) 16 / 23 (69.57%) 11 / 19 (57.89%) 15 / 21 (71.43%) 8 / 13 (61.54%) 0 / 3 (0.00%) 4 / 4 (100.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 3 / 5 (60.00%) 3 / 5 (60.00%)      number of deaths (all causes) 7 4 30 7 1 9 3 12 8 21 16 17 5 0 0 0 0 1 0      number of deaths resulting from adverse events Vascular disorders Hypertension      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hypotension      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Superior vena cava syndrome      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 General disorders and administration site conditions Asthenia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 2 / 2 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 2 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Chest pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Fatigue      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 1 0 / 0 1 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 General physical health deterioration      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Malaise      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Mucosal inflammation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Oedema peripheral      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pyrexia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Sudden death      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Reproductive system and breast disorders Vaginal haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Respiratory, thoracic and mediastinal disorders Dyspnoea      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Epistaxis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Haemothorax      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Paranasal sinus haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pleural effusion      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pneumothorax      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pulmonary embolism      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Respiratory failure      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Psychiatric disorders Confusional state      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Delirium      subjects affected / exposed 0 / 9 (0.00%) 1 / 4 (25.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Suicidal ideation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Investigations Alanine aminotransferase increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Amylase increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Blood creatinine increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Coagulation factor VII level decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 2 / 5 (40.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 2 / 21 (9.52%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 3 / 3 0 / 0 0 / 0 0 / 0 0 / 0 2 / 2 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Ejection fraction decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Lipase increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Prothrombin time prolonged      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 2 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Troponin I increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Injury, poisoning and procedural complications Post procedural haematoma      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Cardiac disorders Atrial fibrillation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Cardiotoxicity      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pericardial effusion      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Thyrotoxic cardiomyopathy      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Nervous system disorders Haemorrhage intracranial      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Ischaemic stroke      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 Loss of consciousness      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Blood and lymphatic system disorders Anaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 2 / 12 (16.67%) 3 / 23 (13.04%) 0 / 19 (0.00%) 1 / 21 (4.76%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 2 / 2 0 / 0 0 / 0 1 / 1 1 / 1 0 / 0 2 / 3 3 / 3 0 / 0 1 / 1 1 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Histiocytosis haematophagic      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Leukopenia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Thrombocytopenia      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 8 / 32 (25.00%) 2 / 9 (22.22%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 4 / 14 (28.57%) 3 / 12 (25.00%) 9 / 23 (39.13%) 4 / 19 (21.05%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 3 / 5 (60.00%) 1 / 5 (20.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 9 / 10 2 / 2 0 / 0 0 / 0 1 / 1 5 / 5 5 / 5 10 / 10 4 / 4 2 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 3 / 3 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Thrombotic microangiopathy      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Gastrointestinal disorders Abdominal pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Colitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Diarrhoea      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 2 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Dysphagia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Gastric haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Gastrointestinal toxicity      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Intestinal perforation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Large intestinal haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Nausea      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 4 / 32 (12.50%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 3 / 23 (13.04%) 2 / 19 (10.53%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 4 / 4 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 2 / 3 2 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Oesophagitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Peritoneal haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Rectal haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Stomatitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Upper gastrointestinal haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Varices oesophageal      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Vomiting      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 4 / 23 (17.39%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 3 / 3 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 3 / 4 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hepatobiliary disorders Hepatic haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hepatitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hepatocellular injury      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hyperbilirubinaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 10 (20.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 2 / 2 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Renal and urinary disorders Acute kidney injury      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Haematuria      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 3 / 23 (13.04%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 3 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Renal failure      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Urinary retention      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Osteonecrosis of jaw      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Infections and infestations Anal abscess      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Catheter site infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Cellulitis      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Clostridium difficile colitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Device related infection      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Escherichia urinary tract infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Herpes zoster      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Oral herpes      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pneumonia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Respiratory tract infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Sepsis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 2 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Upper respiratory tract infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Urinary tract infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Urosepsis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 2 / 23 (8.70%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Metabolism and nutrition disorders Decreased appetite      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Dehydration      subjects affected / exposed 0 / 9 (0.00%) 1 / 4 (25.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 1 / 12 (8.33%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 2 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 1 0 / 1 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Failure to thrive      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hypercalcaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hyperglycaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hypokalaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 1 / 2 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hyponatraemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 0%
Non-serious adverse events Part 1: GSK525762 60 mg QD Part 1: GSK525762 30 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 SCLC Part 2: Participants with NMC Part 2: Participants with CRPC Part 2: Participants with TNBC Part 2: Participants with ER+BC Part 2: Participants with GIST Part 1: GSK525762 2 mg QD Part 1: GSK525762 4 mg QD Part 1: GSK525762 8 mg QD Part 1: GSK525762 16 mg QD 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 subjects affected by non serious adverse events      subjects affected / exposed 9 / 9 (100.00%) 3 / 4 (75.00%) 31 / 32 (96.88%) 9 / 9 (100.00%) 4 / 4 (100.00%) 10 / 10 (100.00%) 5 / 5 (100.00%) 14 / 14 (100.00%) 11 / 12 (91.67%) 23 / 23 (100.00%) 19 / 19 (100.00%) 21 / 21 (100.00%) 12 / 13 (92.31%) 3 / 3 (100.00%) 4 / 4 (100.00%) 1 / 1 (100.00%) 3 / 3 (100.00%) 5 / 5 (100.00%) 5 / 5 (100.00%) Neoplasms benign, malignant and unspecified (incl cysts and polyps) Infected neoplasm      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Tumour pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 2 / 23 (8.70%) 2 / 19 (10.53%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 2 2 1 0 0 0 0 0 0 0 Vascular disorders Flushing      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Haematoma      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 1 0 0 0 1 0 2 0 0 0 0 0 0 0 Hypertension      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 1 / 9 (11.11%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 2 1 0 1 0 0 1 0 0 1 0 1 0 0 0 0 0 Hypotension      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 2 / 5 (40.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 1 0 0 0 0 2 0 Lymphoedema      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 General disorders and administration site conditions Asthenia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 10 / 32 (31.25%) 0 / 9 (0.00%) 1 / 4 (25.00%) 7 / 10 (70.00%) 3 / 5 (60.00%) 4 / 14 (28.57%) 5 / 12 (41.67%) 6 / 23 (26.09%) 7 / 19 (36.84%) 11 / 21 (52.38%) 3 / 13 (23.08%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 13 0 1 8 4 5 6 6 9 12 3 0 0 0 0 0 0 Axillary pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Catheter site inflammation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Catheter site pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 Chest discomfort      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Chest pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 2 / 12 (16.67%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 1 0 0 0 1 2 0 1 0 1 0 0 0 0 0 0 Chills      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 1 / 9 (11.11%) 1 / 4 (25.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 1 1 1 0 0 0 0 0 0 2 0 0 0 0 0 0 1 Face oedema      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 3 / 19 (15.79%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 3 0 0 0 0 0 0 0 0 Facial pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 Fatigue      subjects affected / exposed 3 / 9 (33.33%) 1 / 4 (25.00%) 11 / 32 (34.38%) 5 / 9 (55.56%) 1 / 4 (25.00%) 1 / 10 (10.00%) 1 / 5 (20.00%) 5 / 14 (35.71%) 4 / 12 (33.33%) 12 / 23 (52.17%) 7 / 19 (36.84%) 4 / 21 (19.05%) 3 / 13 (23.08%) 1 / 3 (33.33%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 3 / 5 (60.00%) 3 / 5 (60.00%)      occurrences all number 3 1 12 6 1 1 1 5 4 15 7 4 3 1 1 0 0 3 3 Gait disturbance      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Influenza like illness      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 2 / 19 (10.53%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 2 0 1 0 0 0 0 0 0 Localised oedema      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Malaise      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 2 0 0 1 0 0 0 1 0 2 0 0 0 0 0 0 0 Mucosal inflammation      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 3 / 32 (9.38%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 1 / 12 (8.33%) 2 / 23 (8.70%) 1 / 19 (5.26%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 1 0 3 0 0 0 0 1 1 2 1 0 1 0 0 0 0 0 1 Non-cardiac chest pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 3 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 Oedema peripheral      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 2 / 32 (6.25%) 1 / 9 (11.11%) 0 / 4 (0.00%) 1 / 10 (10.00%) 1 / 5 (20.00%) 1 / 14 (7.14%) 1 / 12 (8.33%) 3 / 23 (13.04%) 3 / 19 (15.79%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 1 0 2 1 0 1 1 1 1 3 3 4 0 0 0 0 0 1 0 Pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 Pyrexia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 6 / 32 (18.75%) 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 10 (20.00%) 0 / 5 (0.00%) 4 / 14 (28.57%) 0 / 12 (0.00%) 1 / 23 (4.35%) 4 / 19 (21.05%) 2 / 21 (9.52%) 0 / 13 (0.00%) 1 / 3 (33.33%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 8 0 0 3 0 6 0 1 4 2 0 1 1 0 0 0 0 Xerosis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Immune system disorders Seasonal allergy      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Reproductive system and breast disorders Benign prostatic hyperplasia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Breast pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Metrorrhagia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Pelvic haematoma      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Pelvic pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Perineal pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Vaginal discharge      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Vaginal odour      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Vulvovaginal pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Respiratory, thoracic and mediastinal disorders Acute respiratory failure      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Cough      subjects affected / exposed 3 / 9 (33.33%) 0 / 4 (0.00%) 4 / 32 (12.50%) 1 / 9 (11.11%) 0 / 4 (0.00%) 3 / 10 (30.00%) 1 / 5 (20.00%) 1 / 14 (7.14%) 3 / 12 (25.00%) 2 / 23 (8.70%) 1 / 19 (5.26%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 3 0 4 2 0 3 1 1 3 2 1 2 0 0 1 0 0 1 0 Dysphonia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 1 / 4 (25.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 1 1 0 1 0 0 1 2 0 0 0 0 0 0 1 Dyspnoea      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 5 / 32 (15.63%) 5 / 9 (55.56%) 0 / 4 (0.00%) 3 / 10 (30.00%) 1 / 5 (20.00%) 4 / 14 (28.57%) 2 / 12 (16.67%) 5 / 23 (21.74%) 4 / 19 (21.05%) 8 / 21 (38.10%) 4 / 13 (30.77%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 2 / 5 (40.00%)      occurrences all number 0 0 7 6 0 4 1 4 2 5 4 8 4 0 0 0 0 1 2 Dyspnoea exertional      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 2 / 23 (8.70%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 1 0 2 0 0 1 0 0 0 0 0 0 Epistaxis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 5 / 32 (15.63%) 2 / 9 (22.22%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 5 / 12 (41.67%) 6 / 23 (26.09%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 1 / 3 (33.33%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 5 2 0 0 0 0 6 6 1 1 0 0 0 0 1 1 0 Haemoptysis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 3 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 0 Laryngeal pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Nasal congestion      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Nasal dryness      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Nocturnal dyspnoea      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Oropharyngeal pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 1 / 3 (33.33%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 1 0 1 0 0 0 0 0 0 1 1 0 Orthopnoea      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Pharyngeal oedema      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Pleural effusion      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Pneumonia aspiration      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Productive cough      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Pulmonary alveolar haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Pulmonary embolism      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Pulmonary haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Respiratory symptom      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rhinitis allergic      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rhinorrhoea      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 Sputum discoloured      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Throat clearing      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Upper-airway cough syndrome      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 1 / 3 (33.33%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 Wheezing      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Psychiatric disorders Agitation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Anhedonia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Anxiety      subjects affected / exposed 0 / 9 (0.00%) 1 / 4 (25.00%) 2 / 32 (6.25%) 1 / 9 (11.11%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 2 / 3 (66.67%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 2 / 5 (40.00%) 0 / 5 (0.00%)      occurrences all number 0 1 2 2 0 2 0 0 0 0 0 1 0 2 0 0 0 2 0 Confusional state      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Delirium      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Depression      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 2 / 9 (22.22%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 2 0 0 0 0 1 0 0 0 0 0 1 0 0 1 0 Disorientation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Hallucination      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Hallucination, visual      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Insomnia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 1 / 12 (8.33%) 0 / 23 (0.00%) 1 / 19 (5.26%) 4 / 21 (19.05%) 1 / 13 (7.69%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 2 / 5 (40.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 1 0 0 0 1 1 0 1 4 1 1 0 0 0 2 1 Mental status changes      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Mood altered      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Investigations Activated partial thromboplastin time prolonged      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 1 / 9 (11.11%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 3 / 21 (14.29%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 1 / 3 (33.33%) 4 / 5 (80.00%) 1 / 5 (20.00%)      occurrences all number 0 0 3 1 0 1 0 0 0 0 0 3 0 0 0 0 1 4 1 Alanine aminotransferase increased      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 4 / 32 (12.50%) 2 / 9 (22.22%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 2 / 14 (14.29%) 1 / 12 (8.33%) 3 / 23 (13.04%) 4 / 19 (21.05%) 4 / 21 (19.05%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 1 / 1 (100.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 5 2 0 0 0 2 1 3 5 4 1 0 0 1 0 0 0 Amylase increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 1 / 12 (8.33%) 2 / 23 (8.70%) 1 / 19 (5.26%) 1 / 21 (4.76%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 2 1 2 1 1 1 0 0 0 0 0 0 Aspartate aminotransferase increased      subjects affected / exposed 1 / 9 (11.11%) 1 / 4 (25.00%) 5 / 32 (15.63%) 2 / 9 (22.22%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 2 / 14 (14.29%) 2 / 12 (16.67%) 6 / 23 (26.09%) 4 / 19 (21.05%) 6 / 21 (28.57%) 2 / 13 (15.38%) 0 / 3 (0.00%) 0 / 4 (0.00%) 1 / 1 (100.00%) 0 / 3 (0.00%) 2 / 5 (40.00%) 0 / 5 (0.00%)      occurrences all number 1 1 6 2 0 0 0 2 3 8 4 7 2 0 0 1 0 6 0 Bacterial test positive      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Bilirubin conjugated increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 2 / 9 (22.22%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 3 / 21 (14.29%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 2 0 0 0 0 1 0 0 3 0 0 0 0 0 1 0 Blood albumin increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Blood alkaline phosphatase increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 1 / 23 (4.35%) 0 / 19 (0.00%) 1 / 21 (4.76%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 1 / 1 (100.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 1 1 0 1 1 0 0 1 0 0 0 Blood bilirubin unconjugated increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Blood chloride decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Blood creatine phosphokinase MB increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Blood creatine phosphokinase increased      subjects affected / exposed 0 / 9 (0.00%) 1 / 4 (25.00%) 1 / 32 (3.13%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 1 / 23 (4.35%) 0 / 19 (0.00%) 3 / 21 (14.29%) 5 / 13 (38.46%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 1 1 2 0 0 0 0 1 1 0 3 6 0 0 0 0 1 0 Blood creatinine increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 3 / 14 (21.43%) 2 / 12 (16.67%) 3 / 23 (13.04%) 0 / 19 (0.00%) 4 / 21 (19.05%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 3 0 0 1 0 3 2 3 0 5 0 0 0 0 0 0 1 Blood fibrinogen decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Blood fibrinogen increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Blood insulin increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Blood thyroid stimulating hormone decreased      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 1 0 0 1 1 0 0 1 1 0 0 0 0 0 0 0 0 Blood triglycerides increased      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 2 / 12 (16.67%) 1 / 23 (4.35%) 2 / 19 (10.53%) 2 / 21 (9.52%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 1 / 5 (20.00%)      occurrences all number 1 0 0 0 0 0 1 0 2 1 2 2 1 0 0 0 0 1 1 Blood uric acid increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Brain natriuretic peptide increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Coagulation factor VII level decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 10 (30.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 3 / 19 (15.79%) 4 / 21 (19.05%) 3 / 13 (23.08%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 3 1 0 1 0 3 6 3 0 0 0 0 0 0 Ejection fraction decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 2 0 0 0 0 0 0 0 Electrocardiogram QRS complex prolonged      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Electrocardiogram QT prolonged      subjects affected / exposed 2 / 9 (22.22%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 2 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Gamma-glutamyltransferase increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 International normalised ratio increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 7 / 32 (21.88%) 2 / 9 (22.22%) 1 / 4 (25.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 4 / 12 (33.33%) 5 / 23 (21.74%) 3 / 19 (15.79%) 4 / 21 (19.05%) 4 / 13 (30.77%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 4 / 5 (80.00%) 1 / 5 (20.00%)      occurrences all number 0 0 7 2 1 0 0 0 4 5 3 4 4 1 0 0 0 4 1 Lipase increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 2 / 14 (14.29%) 0 / 12 (0.00%) 2 / 23 (8.70%) 1 / 19 (5.26%) 0 / 21 (0.00%) 2 / 13 (15.38%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 2 0 0 0 0 2 0 3 1 0 2 0 0 0 0 0 0 N-terminal prohormone brain natriuretic peptide increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 1 1 0 0 0 0 0 0 Occult blood positive      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Oxygen saturation decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Protein urine present      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Prothrombin time prolonged      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 4 / 32 (12.50%) 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 10 (30.00%) 2 / 5 (40.00%) 0 / 14 (0.00%) 3 / 12 (25.00%) 4 / 23 (17.39%) 2 / 19 (10.53%) 4 / 21 (19.05%) 4 / 13 (30.77%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 2 / 5 (40.00%)      occurrences all number 0 0 5 0 0 4 2 0 3 4 3 7 4 0 0 0 0 1 2 Prothrombin time ratio decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Thyroxine free decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Thyroxine free increased      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 2 / 23 (8.70%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 2 1 1 0 0 0 0 0 0 0 Transaminases increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Tri-iodothyronine free decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Troponin T increased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Weight decreased      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 4 / 9 (44.44%) 0 / 4 (0.00%) 3 / 10 (30.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 3 / 12 (25.00%) 2 / 23 (8.70%) 2 / 19 (10.53%) 5 / 21 (23.81%) 2 / 13 (15.38%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 3 5 0 4 2 0 4 2 3 5 2 0 0 0 0 0 1 White blood cells urine positive      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Injury, poisoning and procedural complications Allergic transfusion reaction      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Animal bite      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Contusion      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 3 / 12 (25.00%) 5 / 23 (21.74%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 2 / 5 (40.00%)      occurrences all number 0 0 2 1 0 0 0 0 5 5 0 0 0 0 0 0 0 0 2 Cystitis radiation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Eye contusion      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Fall      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 1 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Genital contusion      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Limb injury      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Postoperative wound complication      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Procedural pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Radiation oesophagitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Transfusion reaction      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Congenital, familial and genetic disorders Factor V deficiency      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Cardiac disorders Atrial fibrillation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nodal rhythm      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Palpitations      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 Pericardial effusion      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Sinus tachycardia      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 2 0 0 1 0 0 0 2 0 1 0 1 0 0 0 0 0 Supraventricular tachycardia      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Tachycardia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 10 (20.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 1 / 5 (20.00%)      occurrences all number 0 0 2 0 0 3 1 0 0 1 1 0 0 1 0 0 0 1 1 Nervous system disorders Ageusia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Aphasia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 1 Balance disorder      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Cervical radiculopathy      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Dizziness      subjects affected / exposed 0 / 9 (0.00%) 1 / 4 (25.00%) 3 / 32 (9.38%) 2 / 9 (22.22%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 1 / 19 (5.26%) 4 / 21 (19.05%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 1 3 3 0 2 0 0 0 1 1 4 0 0 0 0 0 0 0 Drug withdrawal headache      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Dysaesthesia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Dysgeusia      subjects affected / exposed 3 / 9 (33.33%) 1 / 4 (25.00%) 8 / 32 (25.00%) 5 / 9 (55.56%) 1 / 4 (25.00%) 4 / 10 (40.00%) 2 / 5 (40.00%) 2 / 14 (14.29%) 4 / 12 (33.33%) 10 / 23 (43.48%) 5 / 19 (26.32%) 7 / 21 (33.33%) 5 / 13 (38.46%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 2 / 5 (40.00%) 3 / 5 (60.00%)      occurrences all number 5 1 9 6 1 4 2 2 4 12 6 8 5 0 0 0 0 2 3 Headache      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 3 / 32 (9.38%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 3 / 12 (25.00%) 1 / 23 (4.35%) 4 / 19 (21.05%) 2 / 21 (9.52%) 3 / 13 (23.08%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 1 0 5 1 0 0 0 0 4 1 4 2 3 0 1 0 0 0 1 Intercostal neuralgia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Lethargy      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Loss of consciousness      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Neuralgia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 Neuropathy peripheral      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 1 0 0 0 0 0 0 0 Paraesthesia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Post herpetic neuralgia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Presyncope      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Sciatica      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Somnolence      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 3 0 0 1 1 0 0 0 1 1 0 0 1 0 0 0 0 Syncope      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Tension headache      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Tremor      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Blood and lymphatic system disorders Anaemia      subjects affected / exposed 1 / 9 (11.11%) 1 / 4 (25.00%) 11 / 32 (34.38%) 5 / 9 (55.56%) 2 / 4 (50.00%) 4 / 10 (40.00%) 1 / 5 (20.00%) 6 / 14 (42.86%) 3 / 12 (25.00%) 13 / 23 (56.52%) 7 / 19 (36.84%) 9 / 21 (42.86%) 2 / 13 (15.38%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 4 / 5 (80.00%) 3 / 5 (60.00%)      occurrences all number 1 2 14 5 2 4 2 6 3 14 7 11 2 0 0 0 0 4 3 Haemorrhagic diathesis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 2 / 23 (8.70%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 Increased tendency to bruise      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Leukocytosis      subjects affected / exposed 0 / 9 (0.00%) 1 / 4 (25.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Leukopenia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 3 / 5 (60.00%) 1 / 5 (20.00%)      occurrences all number 0 0 2 1 0 0 0 0 1 0 0 1 0 0 0 0 0 3 1 Lymphopenia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 4 / 32 (12.50%) 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 10 (20.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 3 / 23 (13.04%) 2 / 19 (10.53%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 7 0 0 4 1 0 1 3 2 1 0 0 0 0 0 0 0 Neutropenia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 3 / 14 (21.43%) 2 / 12 (16.67%) 1 / 23 (4.35%) 1 / 19 (5.26%) 4 / 21 (19.05%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 3 1 0 0 0 3 2 2 1 4 1 0 0 0 0 1 0 Thrombocytopenia      subjects affected / exposed 2 / 9 (22.22%) 1 / 4 (25.00%) 18 / 32 (56.25%) 5 / 9 (55.56%) 1 / 4 (25.00%) 7 / 10 (70.00%) 5 / 5 (100.00%) 7 / 14 (50.00%) 3 / 12 (25.00%) 12 / 23 (52.17%) 13 / 19 (68.42%) 13 / 21 (61.90%) 3 / 13 (23.08%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 4 / 5 (80.00%) 3 / 5 (60.00%)      occurrences all number 2 1 39 8 1 8 5 12 5 23 15 18 3 0 1 0 0 4 3 Ear and labyrinth disorders Ear haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Hypoacusis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 Vertigo      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 1 0 1 2 0 0 0 0 0 0 0 Eye disorders Cataract      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Diplopia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Dry eye      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Eye pruritus      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Keratitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Optic neuropathy      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Orbital oedema      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Vision blurred      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 4 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 Visual acuity reduced      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Vitreous floaters      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Xerophthalmia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Gastrointestinal disorders Abdominal discomfort      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Abdominal distension      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 Abdominal hernia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Abdominal pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 4 / 32 (12.50%) 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 10 (20.00%) 2 / 5 (40.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 1 / 21 (4.76%) 2 / 13 (15.38%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 1 / 5 (20.00%)      occurrences all number 0 0 4 0 0 2 2 1 0 0 1 1 3 1 0 0 0 2 1 Abdominal pain lower      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Abdominal pain upper      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 2 / 12 (16.67%) 1 / 23 (4.35%) 0 / 19 (0.00%) 5 / 21 (23.81%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 2 / 5 (40.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 1 0 0 2 2 0 6 0 0 0 0 0 2 0 Abdominal tenderness      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Anal fissure      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Anal inflammation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Anorectal discomfort      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Ascites      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Chapped lips      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Cheilitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 2 0 1 0 0 0 0 0 0 Colitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Constipation      subjects affected / exposed 2 / 9 (22.22%) 1 / 4 (25.00%) 1 / 32 (3.13%) 3 / 9 (33.33%) 1 / 4 (25.00%) 2 / 10 (20.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 3 / 12 (25.00%) 5 / 23 (21.74%) 5 / 19 (26.32%) 1 / 21 (4.76%) 2 / 13 (15.38%) 0 / 3 (0.00%) 3 / 4 (75.00%) 0 / 1 (0.00%) 1 / 3 (33.33%) 4 / 5 (80.00%) 0 / 5 (0.00%)      occurrences all number 2 1 1 3 1 3 0 1 3 5 6 2 2 0 3 0 1 4 0 Diarrhoea      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 11 / 32 (34.38%) 4 / 9 (44.44%) 0 / 4 (0.00%) 6 / 10 (60.00%) 5 / 5 (100.00%) 4 / 14 (28.57%) 6 / 12 (50.00%) 12 / 23 (52.17%) 7 / 19 (36.84%) 8 / 21 (38.10%) 4 / 13 (30.77%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 3 / 5 (60.00%) 1 / 5 (20.00%)      occurrences all number 2 0 16 5 0 10 8 6 8 24 7 11 5 1 0 0 0 5 1 Dry mouth      subjects affected / exposed 0 / 9 (0.00%) 2 / 4 (50.00%) 3 / 32 (9.38%) 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 10 (30.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 2 / 12 (16.67%) 3 / 23 (13.04%) 1 / 19 (5.26%) 3 / 21 (14.29%) 1 / 13 (7.69%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 2 / 3 (66.67%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 2 4 0 0 3 1 0 2 3 1 4 1 0 1 0 2 0 1 Dyspepsia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 1 1 0 1 0 0 0 1 0 Dysphagia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 Eructation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Faeces discoloured      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Faeces soft      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Flatulence      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 1 / 23 (4.35%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 1 / 3 (33.33%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 1 1 1 1 0 1 1 0 0 0 0 Frequent bowel movements      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Gastric haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Gastric ulcer      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 1 / 4 (25.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Gastrointestinal fistula      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Gastrointestinal haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Gastrooesophageal reflux disease      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Gingival bleeding      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 6 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Gingival pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Glossitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Haematemesis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 1 / 4 (25.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Haemorrhoids      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Hypoaesthesia oral      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Impaired gastric emptying      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 Lip dry      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Mouth ulceration      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 1 Nausea      subjects affected / exposed 2 / 9 (22.22%) 3 / 4 (75.00%) 15 / 32 (46.88%) 7 / 9 (77.78%) 2 / 4 (50.00%) 6 / 10 (60.00%) 1 / 5 (20.00%) 8 / 14 (57.14%) 5 / 12 (41.67%) 11 / 23 (47.83%) 8 / 19 (42.11%) 9 / 21 (42.86%) 5 / 13 (38.46%) 0 / 3 (0.00%) 1 / 4 (25.00%) 1 / 1 (100.00%) 1 / 3 (33.33%) 3 / 5 (60.00%) 1 / 5 (20.00%)      occurrences all number 2 3 19 10 2 9 2 8 6 16 12 12 5 0 1 2 1 4 1 Odynophagia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Oesophagitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Perianal erythema      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rectal haemorrhage      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 Stomatitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 10 (30.00%) 0 / 5 (0.00%) 2 / 14 (14.29%) 1 / 12 (8.33%) 1 / 23 (4.35%) 1 / 19 (5.26%) 3 / 21 (14.29%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 2 0 0 3 0 3 1 1 1 3 1 0 0 0 0 1 0 Toothache      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Vomiting      subjects affected / exposed 2 / 9 (22.22%) 1 / 4 (25.00%) 11 / 32 (34.38%) 4 / 9 (44.44%) 3 / 4 (75.00%) 3 / 10 (30.00%) 1 / 5 (20.00%) 4 / 14 (28.57%) 4 / 12 (33.33%) 9 / 23 (39.13%) 8 / 19 (42.11%) 6 / 21 (28.57%) 2 / 13 (15.38%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 2 / 3 (66.67%) 3 / 5 (60.00%) 1 / 5 (20.00%)      occurrences all number 2 1 20 5 3 6 1 4 5 18 11 8 2 0 1 0 2 3 1 Hepatobiliary disorders Cholangitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Hepatic pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Hyperbilirubinaemia      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 9 / 32 (28.13%) 5 / 9 (55.56%) 1 / 4 (25.00%) 4 / 10 (40.00%) 2 / 5 (40.00%) 4 / 14 (28.57%) 5 / 12 (41.67%) 7 / 23 (30.43%) 2 / 19 (10.53%) 9 / 21 (42.86%) 2 / 13 (15.38%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 2 / 5 (40.00%) 2 / 5 (40.00%)      occurrences all number 1 0 11 6 1 4 3 5 6 9 3 12 2 0 0 0 0 2 2 Liver disorder      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Portal vein thrombosis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Skin and subcutaneous tissue disorders Alopecia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 Blister      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Dermatitis acneiform      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 3 / 32 (9.38%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 3 1 0 0 0 0 1 0 0 2 0 0 0 0 0 0 0 Dermatitis bullous      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Dermatitis contact      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Dry skin      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 2 / 32 (6.25%) 1 / 9 (11.11%) 0 / 4 (0.00%) 2 / 10 (20.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 3 / 19 (15.79%) 1 / 21 (4.76%) 0 / 13 (0.00%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 2 1 0 2 1 0 1 0 3 1 0 1 0 0 0 0 0 Ecchymosis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 1 0 Erythema      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 1 0 0 1 1 0 0 0 0 0 0 0 Guttate psoriasis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Hair colour changes      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Hidradenitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Hyperhidrosis      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 1 0 0 1 0 0 0 0 0 0 Ingrowing nail      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Leukoplakia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Madarosis      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Night sweats      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Onycholysis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Palmar-plantar erythrodysaesthesia syndrome      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Petechiae      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 Pigmentation disorder      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Pruritus      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 2 / 32 (6.25%) 1 / 9 (11.11%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 3 / 14 (21.43%) 1 / 12 (8.33%) 0 / 23 (0.00%) 4 / 19 (21.05%) 1 / 21 (4.76%) 0 / 13 (0.00%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 2 1 0 1 0 4 1 0 5 1 0 1 0 0 0 0 0 Purpura      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Rash      subjects affected / exposed 2 / 9 (22.22%) 0 / 4 (0.00%) 5 / 32 (15.63%) 2 / 9 (22.22%) 0 / 4 (0.00%) 2 / 10 (20.00%) 0 / 5 (0.00%) 4 / 14 (28.57%) 5 / 12 (41.67%) 1 / 23 (4.35%) 1 / 19 (5.26%) 3 / 21 (14.29%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 1 / 5 (20.00%)      occurrences all number 2 0 5 2 0 3 0 5 5 1 1 4 0 0 0 0 0 1 1 Rash erythematous      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rash macular      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Rash maculo-papular      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 2 / 14 (14.29%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 2 0 1 0 0 0 0 0 0 0 0 0 Rash papular      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rash pruritic      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 0 1 Scab      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Seborrhoeic dermatitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Skin burning sensation      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Skin fissures      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Skin hyperpigmentation      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Skin lesion      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 Skin ulcer      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 1 / 3 (33.33%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 Urticaria      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Renal and urinary disorders Acute kidney injury      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 3 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 Anuria      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Chromaturia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 1 / 5 (20.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 Dysuria      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 3 / 32 (9.38%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 1 / 12 (8.33%) 2 / 23 (8.70%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 3 0 0 0 0 1 1 2 0 0 1 0 0 0 0 0 0 Haematuria      subjects affected / exposed 0 / 9 (0.00%) 1 / 4 (25.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 7 / 23 (30.43%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 1 0 0 0 1 0 0 0 10 0 0 0 0 0 0 0 0 0 Hydronephrosis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Hypertonic bladder      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Neurogenic bladder      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nocturia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Proteinuria      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 1 0 Urinary hesitation      subjects affected / exposed 0 / 9 (0.00%) 1 / 4 (25.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Urinary retention      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Urinary tract disorder      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Urine odour abnormal      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Endocrine disorders Hyperthyroidism      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 2 / 12 (16.67%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 3 0 0 0 0 0 2 0 0 1 0 0 0 0 0 0 1 Arthritis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 Back pain      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 4 / 32 (12.50%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 4 / 23 (17.39%) 0 / 19 (0.00%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 1 0 6 1 0 0 0 0 0 4 0 2 0 0 0 0 0 0 1 Bone pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 2 / 12 (16.67%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 1 0 0 0 0 2 0 0 0 1 0 0 0 0 0 0 Connective tissue disorder      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Groin pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Joint swelling      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Muscle spasms      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 3 / 23 (13.04%) 1 / 19 (5.26%) 3 / 21 (14.29%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 1 0 2 3 1 3 0 0 0 0 0 0 0 Musculoskeletal chest pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 4 1 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 Musculoskeletal disorder      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Musculoskeletal pain      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 1 / 19 (5.26%) 2 / 21 (9.52%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 1 / 5 (20.00%)      occurrences all number 0 0 1 1 0 0 1 0 1 0 1 2 0 0 0 0 0 1 1 Myalgia      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 4 / 23 (17.39%) 3 / 19 (15.79%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 1 / 5 (20.00%)      occurrences all number 1 0 1 0 0 0 0 0 1 4 3 0 0 0 0 0 0 1 1 Pain in extremity      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 2 1 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 Pain in jaw      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Infections and infestations Anal abscess      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Angular cheilitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 Bronchitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Catheter site infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Cellulitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Conjunctivitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Cystitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 Device related infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 10 (20.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 Ear infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Endometritis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Folliculitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Fungal skin infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Genital herpes simplex      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Gingivitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Herpes dermatitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Herpes virus infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Herpes zoster      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 2 / 21 (9.52%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 2 0 0 1 0 1 0 1 0 2 1 0 0 0 0 0 0 Infected cyst      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Infected skin ulcer      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Lip infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Lower respiratory tract infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Lung infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 1 0 0 1 1 0 0 0 0 0 0 0 Nail infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Nasopharyngitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Oral candidiasis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Oral herpes      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 1 / 19 (5.26%) 1 / 21 (4.76%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 4 0 0 1 1 0 0 1 1 1 1 0 0 0 0 0 0 Otitis media      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Pharyngitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Pneumonia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Respiratory tract infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rhinitis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Rhinovirus infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Sepsis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Skin candida      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Skin infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 Subcutaneous abscess      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Upper respiratory tract infection      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 1 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Urinary tract infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 3 / 32 (9.38%) 1 / 9 (11.11%) 1 / 4 (25.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 4 / 23 (17.39%) 3 / 19 (15.79%) 0 / 21 (0.00%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 3 1 1 0 0 1 0 7 3 0 1 0 0 0 0 0 0 Vaginal infection      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Metabolism and nutrition disorders Decreased appetite      subjects affected / exposed 2 / 9 (22.22%) 1 / 4 (25.00%) 15 / 32 (46.88%) 6 / 9 (66.67%) 1 / 4 (25.00%) 7 / 10 (70.00%) 4 / 5 (80.00%) 5 / 14 (35.71%) 4 / 12 (33.33%) 15 / 23 (65.22%) 8 / 19 (42.11%) 10 / 21 (47.62%) 6 / 13 (46.15%) 0 / 3 (0.00%) 2 / 4 (50.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 2 / 5 (40.00%)      occurrences all number 2 1 19 8 1 10 5 5 4 16 8 11 6 0 2 0 0 1 2 Dehydration      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 2 / 9 (22.22%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 3 / 14 (21.43%) 0 / 12 (0.00%) 2 / 23 (8.70%) 0 / 19 (0.00%) 2 / 21 (9.52%) 1 / 13 (7.69%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 2 2 0 0 0 3 0 2 0 2 1 0 1 0 0 1 0 Hypercalcaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Hypercholesterolaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 2 / 21 (9.52%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 2 0 0 0 0 0 0 0 0 2 1 0 0 0 0 1 0 Hyperglycaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 6 / 32 (18.75%) 1 / 9 (11.11%) 1 / 4 (25.00%) 4 / 10 (40.00%) 1 / 5 (20.00%) 1 / 14 (7.14%) 2 / 12 (16.67%) 2 / 23 (8.70%) 3 / 19 (15.79%) 6 / 21 (28.57%) 5 / 13 (38.46%) 0 / 3 (0.00%) 0 / 4 (0.00%) 1 / 1 (100.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 2 / 5 (40.00%)      occurrences all number 0 0 6 1 1 7 1 1 2 2 4 7 5 0 0 1 0 1 2 Hyperkalaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 0 Hypermagnesaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 1 / 9 (11.11%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Hyperphosphataemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 1 / 12 (8.33%) 1 / 23 (4.35%) 0 / 19 (0.00%) 1 / 21 (4.76%) 1 / 13 (7.69%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 1 / 5 (20.00%)      occurrences all number 0 0 2 0 0 0 0 1 1 1 0 1 1 0 0 0 0 0 1 Hypertriglyceridaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 1 / 23 (4.35%) 1 / 19 (5.26%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 1 1 1 0 0 0 1 0 0 0 0 Hypoalbuminaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 2 / 10 (20.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 1 / 23 (4.35%) 3 / 19 (15.79%) 2 / 21 (9.52%) 0 / 13 (0.00%) 1 / 3 (33.33%) 2 / 4 (50.00%) 0 / 1 (0.00%) 1 / 3 (33.33%) 2 / 5 (40.00%) 0 / 5 (0.00%)      occurrences all number 0 0 3 0 0 2 0 0 1 1 3 3 0 1 2 0 1 2 0 Hypocalcaemia      subjects affected / exposed 1 / 9 (11.11%) 0 / 4 (0.00%) 2 / 32 (6.25%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 1 / 23 (4.35%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 1 0 2 0 0 1 0 0 1 1 0 0 0 0 1 0 0 1 0 Hypocholesterolaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 1 / 5 (20.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Hypokalaemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 5 / 32 (15.63%) 1 / 9 (11.11%) 1 / 4 (25.00%) 4 / 10 (40.00%) 0 / 5 (0.00%) 2 / 14 (14.29%) 0 / 12 (0.00%) 3 / 23 (13.04%) 1 / 19 (5.26%) 1 / 21 (4.76%) 1 / 13 (7.69%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 1 / 3 (33.33%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 6 1 1 4 0 2 0 4 1 1 1 0 1 0 1 1 0 Hypomagnesaemia      subjects affected / exposed 0 / 9 (0.00%) 1 / 4 (25.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 1 / 12 (8.33%) 0 / 23 (0.00%) 1 / 19 (5.26%) 1 / 21 (4.76%) 0 / 13 (0.00%) 0 / 3 (0.00%) 2 / 4 (50.00%) 1 / 1 (100.00%) 0 / 3 (0.00%) 2 / 5 (40.00%) 0 / 5 (0.00%)      occurrences all number 0 1 1 0 0 1 0 0 1 0 1 1 0 0 2 1 0 2 0 Hyponatraemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 4 / 32 (12.50%) 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 10 (10.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 1 / 12 (8.33%) 1 / 23 (4.35%) 2 / 19 (10.53%) 2 / 21 (9.52%) 1 / 13 (7.69%) 1 / 3 (33.33%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 4 0 0 1 0 1 1 1 2 2 1 1 1 0 0 1 0 Hypophosphataemia      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 1 / 14 (7.14%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 1 / 4 (25.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 Iron deficiency      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 1 / 32 (3.13%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 0 / 5 (0.00%) 0 / 5 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Metabolic acidosis      subjects affected / exposed 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 32 (0.00%) 0 / 9 (0.00%) 0 / 4 (0.00%) 0 / 10 (0.00%) 0 / 5 (0.00%) 0 / 14 (0.00%) 0 / 12 (0.00%) 0 / 23 (0.00%) 0 / 19 (0.00%) 0 / 21 (0.00%) 0 / 13 (0.00%) 0 / 3 (0.00%) 0 / 4 (0.00%) 0 / 1 (0.00%) 0 / 3 (0.00%) 1 / 5 (20.00%) 0 / 5 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0

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Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
09 Jan 2012	Amendment 1: Modifications include updated medical monitoring information due to a personnel change on the GSK team. In addition, following review of the protocol by the FDA, the following changes are made: For Part 1, the starting dose of GSK525762 is reduced from 5 mg/day to 2 mg/day. Cardiac troponin T level assessments are required as a part of the inclusion criteria and thereafter. An observation of CTCAE Grade 2 drug related toxicity, including grade 2 troponin T elevation, in one participant will end accelerated dose titration in Part 1. Participants with a history of gastrointestinal bleeding or active bleeding (positive guaiac fecal occult blood monitoring) will be excluded. In addition, wording for dose escalation decisions has been modified to state that no more than a 2-fold increase in dose will occur between successive cohorts. A staggered dosing approach will be implemented in the 3+3 dosing design to minimize potential for toxicity in multiple participants. Alternative dosing regimens will not be implemented without consultation with FDA and a protocol amendment. For Part 2 of the trial, stopping rules based on lack of efficacy and the futility rule have been modified. Additionally the disease assessment scans may be reviewed retrospectively by an independent radiologist. Finally, multiple Time and Event Tables have been revised for consistency across Part 1 and Part 2 of the protocol.
29 Aug 2012	Changes via Amendment 2 include the addition of participants with tumor types other than NMC [including multiple myeloma (MM), small cell lung cancer (SCLC), colorectal cancer (CRC), neuroblastoma (NB), and any solid tumor that demonstrates N-Myc amplification or over expression (such as NSCLC with N-myc amplification)] and associated changes in the study design and inclusion criteria; definition of adult participants as those 16 and older; addition of pediatric participants 12 to ≤15 years old; modification of the initial staggered dosing schedule to shorten the dose escalation period from 6 weeks to 4 weeks; allowance for treatment beyond tumor progression (decision made in consultation with GSK Medical Monitor); minor clarifications to the Risk Assessment section; updates to Exploratory Objectives/Endpoints to ensure adequate assessment of the effect of drug on tumor biology; and addition of drug preparation guidelines for GSK525762 administered via an enteral feeding tube.
04 Feb 2014	Amendment 3 applies to all study sites and includes the addition of the NMC Pharmacodynamic (PD) Expansion Cohort to evaluate the pharmacodynamic effects of GSK525762 across the predicted efficacious dose range at doses that have been previously cleared during 3+3 dose escalation. The collection of ECGs, PK samples and liver chemistry were clarified or corrected. The inclusion of a pediatric cohort in Part1B, implemented in protocol amendment 2, was clarified and emphasis was added regarding the preservation of reproductive capacity.
06 Oct 2014	Amendment 4 applies to all study sites and includes the addition of participants with the following solid tumor types: castration-resistant prostate cancer (CRPC), triple negative breast cancer (TNBC), estrogen receptor positive breast cancer (ER positive), and non-small cell lung cancer (NSCLC). Multiple myeloma (MM), a hematological malignancy previously included in the trial, is now removed from this trial as it is included in a separate trial open for hematologic malignancies with dose escalation to better define the benefit/risk balance. Additional details of twice daily (BID) dosing during dose escalation have been included. A Besylate Sub-Study has been added to determine the relative bioavailability (BA), food effect, and dose proportionality of the besylate formulation of GSK525762 at or near the maximum tolerated dose (MTD). An update to inclusion criteria has been made to allow participants with evaluable disease to be enrolled in the NMC PD cohort. An updated imaging schedule for NMC participants has been included.
24 Mar 2015	Amendment 5 applies to all study sites and includes the following additional expansion cohorts for Part 2 of the trial: castration-resistant prostate cancer (CRPC), triple negative breast cancer (TNBC), estrogen receptor positive breast cancer (ER positive) and small cell lung cancer (SCLC). An update was included regarding the Besylate Sub-Study to clarify that this sub-study would only be conducted at centers in the United States. The pediatric cohort in Part 1B was removed for further evaluation in a separate study. An update to the QTc management guidelines has been included.
19 Jun 2015	Amendment 6 applies to all study sites and includes updated guidance on contraception use based on emerging data from preclinical studies. Clarified how the Holter monitoring data will be reviewed and analyzed. Additionally, updates were made throughout to correct minor inconsistencies and provide further clarification, specifically with the Time and Events Tables. Furthermore, the dosing schedule was updated from a staggered (1,3,5,7) dosing schedule in the first two weeks to a continuous daily dosing schedule. Finally, after an internal QTc analysis and evaluation of cardiac safety data collected from all participants up to the 100 mg QD cohort available by 15-May-2015, the 48-hour telemetry requirement has been removed for all parts of the study and the frequency of Holter monitoring has been decreased in Part 1.
10 Mar 2016	Amendment 7 updates were made, to include the final dose and regimen for Part 2, which was determined to be 75 mg once daily based on emerging data from Part 1 and Besylate Sub-Study; to clarify that the besylate salt tablets will be the formulation used for participants enrolled in Part 2 (and potentially for ongoing or newly enrolled participants in Part 1); to update required number of participants to be enrolled in the Part 1; to update the subject and study completion details; to update the Visit window for Discontinuation and End of Treatment; to update diagnosis criteria of NMC for Part 1 and 2 for NMC subjects; to update dosing, handling and storage instruction for GSK525762 Besylate tablet; to modify the meals and dietary restrictions based on the results of the besylate sub-study, the fasting requirement is being lifted , except on Serial PK sampling days in Part 2 (Week 1 and Week 4); to include the details about interim and final analysis. Additionally, following updates were in the time and event table, 12-lead ECGs monitoring for prolonged QTcF for Part 1 and 2 was updated, tumor sampling time point was updated for Part 1 and 2; optional Sweat PK sampling for Part1 was removed; optional saliva sampling for time points for part 1 was updated; pain assessments was included for Part 2; Week1 Day1, echocardiogram (ECHO) was made optional for Part 2; and computed tomography (CT) scan, magnetic resonance imaging (MRI) and positron emission tomography (PET) scan detail were updated for Part 2.
02 Dec 2016	Amendment 8 includes changes as the result of the Dear Investigator Letter, dated 16 November 2016 which outlines the updated thrombocytopenia management guidelines, as outlined in the Dear Investigator Letter, dated 16 November 2016. This amendment also includes increased coagulation monitoring for Part 2 (added at Week2 Day1, Week3 Day1 and changed from once every 8 weeks [q8W] to once every 4 weeks [q4W] after Week 13), addition of Factor VII monitoring in Part 2 (at Screening, Week3 Day1 and reflex testing if PT or INR are ≥1.5 times ULN) and addition of laboratory values required prior to performing the post-dose biopsy.
24 Feb 2017	Amendment 9: The following changes have been made: addition of exclusion criteria for exclusionary medications; updated exclusion of bleeding to include all history of bleeding and added known bleeding disorders; addition of laboratory monitoring required prior to surgeries; addition of guidance for dose reduction levels; updated dose adjustment/stopping safety criteria; updated prohibited medications. In addition, other changes include: addition of a GIST cohort in Part 2, including background information, updated endpoints, overall Part 2 sample size, futility information, eligibility criteria and, Data Analysis and Statistical Considerations; updated Risk Assessment to include current available data; removal of cytokines throughout protocol; updated sample size for MTD dose level in Part 1; update to contraception use in Inclusion and clarifications in Lifestyle Requirements; removal of Holter monitoring; changes to Part 1 Time and Events Tables which includes removal of certain ECG time points, change from required to optional for urine PK samples and certain PK/ECG/biomarker tests, addition of Factor VII assay testing, additional lab samples at Week 7 and Week 11, change in timing of on-treatment biopsy; changes to Part 2 Time and Events Tables which includes additional lab samples at Week 7 and 11 and increase in Factor VII testing, addition of pregnancy/testosterone test at W1D1; change in timing of on-treatment biopsy and removal of an ECHO time point; change to the pregnancy reporting guidelines to 24 hours; addition of wording that subjects are to abstain from consuming certain fruits; updates to Concomitant Medications and Non-Drug Therapies to reorganize and update the prohibited, cautionary medication tables and drug interaction information; removal of fever and diarrhea information. Additionally, Appendix was updated with the current GSK Liver Event and follow-up information, but the liver event criteria did not change.
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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