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Clinical Trial Results:
Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy

Summary
EudraCT number	2004-000193-31
Trial protocol	GB
Global end of trial date

Results information
Results version number	v2(current)
This version publication date	13 Aug 2023
First version publication date	27 Feb 2021
Other versions	v1
Version creation reason	New data added to full data set Adding recently completed arms of the STAMPEDE trial

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

PR08

ISRCTN number

ISRCTN78818544

US NCT number

NCT00268476

WHO universal trial number (UTN)

Other trial identifiers

CTA: 20363/0404/001, MREC: 04/MRE07/35, Previous IRAS (Minimal Data Set): 31586

Sponsor organisation name

University College London

Sponsor organisation address

Gower Street, London, United Kingdom, WC1E6BT

Public contact

STAMPEDE Trial Team, MRCCTU at UCL, mrcctu.stampede@ucl.ac.uk

Scientific contact

STAMPEDE Trial Team, MRCCTU at UCL, 44 20 7670 4938, laura.murphy@ucl.ac.uk

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Interim

Date of interim/final analysis

19 May 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Main objective of the trial

This study aims to look at how to improve the way in which prostate cancer is currently managed i.e. by adding new treatments to the standard of care, whether it can enable men to live longer or, by modifying the type of hormone therapy, live at least as long and enjoy a better quality of life. The principal research question for most arms is whether the treatment concerned improves overall survival; however some comparisons such as metformin are being looked at for other reasons.

Protection of trial subjects

In routine care

Background therapy

Evidence for comparator

Actual start date of recruitment

04 Oct 2004

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Switzerland: 49

Country: Number of subjects enrolled

United Kingdom: 7052

Worldwide total number of subjects

7101

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

2658

From 65 to 84 years

4439

85 years and over

Subject disposition

Top of page

Recruitment details

First patient randomised 17Oct2005

Screening details

Screening data not available centrally

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Not blinded

Are arms mutually exclusive

Arm A (SOC for B,C,E comparisons)

Arm description

Reference patients for A vs B, C , E

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Arm B

Arm description

Zoledronic acid

Arm type

Experimental

Investigational medicinal product name

Zoledronic acid

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion in administration system

Routes of administration

Intravenous use

Dosage and administration details

4mg at six 3-weekly cycles, then 4-weekly until 2 years

Arm C

Arm description

Docetaxel

Arm type

Experimental

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

75mg/m2 for six 3-weekly cycles

Arm E

Arm description

Zoledronic Acid and Docetaxel

Arm type

Experimental

Investigational medicinal product name

Zoledronic acid

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion in administration system

Routes of administration

Intravenous use

Dosage and administration details

4mg at six 3-weekly cycles, then 4-weekly until 2 years

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion in administration system

Routes of administration

Intravenous use

Dosage and administration details

75mg/m2 for six 3-weekly cycles

Arm A (SOC for D,F comparisons)

Arm description

Reference patients for A vs D, F

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Arm D

Arm description

Celecoxib

Arm type

Experimental

Investigational medicinal product name

Celecoxib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

400mg twice a day for 1 year

Arm F

Arm description

Zoledronic Acid and Celecoxib

Arm type

Experimental

Investigational medicinal product name

Zoledronic acid

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion in administration system

Routes of administration

Intravenous use

Dosage and administration details

4mg at six 3-weekly cycles, then 4-weekly until 2 years

Investigational medicinal product name

Celecoxib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

400mg twice a day for 1 year

Arm A (SOC - G comparison)

Arm description

Reference patients for arm G

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Arm G

Arm description

Abiraterone

Arm type

Experimental

Investigational medicinal product name

Abiraterone

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1000mg

Investigational medicinal product name

Prednisolone

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

5mg

Arm A (SOC - J comparison)

Arm description

Reference patients for J comparison

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Arm J

Arm description

Enzalutamide and Abiraterone

Arm type

Experimental

Investigational medicinal product name

Enzalutamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

160mg

Investigational medicinal product name

Abiraterone

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1000mg

Investigational medicinal product name

Prednisolone

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

5mg

Number of subjects in period 1	Arm A (SOC for B,C,E comparisons)	Arm B	Arm C	Arm E	Arm A (SOC for D,F comparisons)	Arm D	Arm F	Arm A (SOC - G comparison)	Arm G	Arm A (SOC - J comparison)	Arm J
Started	1184	593	592	593	622	312	311	957	960	987	989
Completed	1184	593	592	593	622	312	311	957	960	987	989

Baseline characteristics

Top of page

Reporting group title

Arm A (SOC for B,C,E comparisons)

Reporting group description

Reference patients for A vs B, C , E

Reporting group title

Arm B

Reporting group description

Zoledronic acid

Reporting group title

Arm C

Reporting group description

Docetaxel

Reporting group title

Arm E

Reporting group description

Zoledronic Acid and Docetaxel

Reporting group title

Arm A (SOC for D,F comparisons)

Reporting group description

Reference patients for A vs D, F

Reporting group title

Arm D

Reporting group description

Celecoxib

Reporting group title

Arm F

Reporting group description

Zoledronic Acid and Celecoxib

Reporting group title

Arm A (SOC - G comparison)

Reporting group description

Reference patients for arm G

Reporting group title

Arm G

Reporting group description

Abiraterone

Reporting group title

Arm A (SOC - J comparison)

Reporting group description

Reference patients for J comparison

Reporting group title

Arm J

Reporting group description

Enzalutamide and Abiraterone

Reporting group values	Arm A (SOC for B,C,E comparisons)	Arm B	Arm C	Arm E	Arm A (SOC for D,F comparisons)	Arm D	Arm F	Arm A (SOC - G comparison)	Arm G	Arm A (SOC - J comparison)	Arm J	Total
Number of subjects	1184	593	592	593	622	312	311	957	960	987	989	7101
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	521	265	270	252	294	139	146	322	326	269	291	2658
From 65-84 years	663	328	322	341	328	173	164	635	633	717	697	4439
85 years and over	0	0	0	0	0	0	1	0	1	1	1	4
Gender categorical
Units: Subjects
Female	0	0	0	0	0	0	0	0	0	0	0	0
Male	1184	593	592	593	622	312	311	957	960	987	989	7101

Subject analysis set title

Arm A (SOC for B,C,E comparisons)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Reference patients (ABCE comparison)

Subject analysis set title

Arm B (ZA)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Experimental group, AB comparison

Subject analysis set title

Arm C (doce)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Arm A vs C

Subject analysis set title

Arm E (doce+ZA)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Docetaxel and Zoledronic acid

Subject analysis set title

Arm A (SOC for D,F comparisons)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Reference patients (ADF comparisons)

Subject analysis set title

Arm D (cel)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Arm A vs D

Subject analysis set title

Arm F (cel+ZA)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Arm A vs F

Subject analysis set title

Arm A (SOC G comparison)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Control arm for G comparison

Subject analysis set title

Arm G

Subject analysis set type

Intention-to-treat

Subject analysis set description

Abiraterone + prednisolone

Subject analysis set title

Arm A (SOC J comparison)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Reference patients for A vs J

Subject analysis set title

Arm J

Subject analysis set type

Intention-to-treat

Subject analysis set description

Enzalutamide and Abiraterone

Subject analysis sets values	Arm A (SOC for B,C,E comparisons)	Arm B (ZA)	Arm C (doce)	Arm E (doce+ZA)	Arm A (SOC for D,F comparisons)	Arm D (cel)	Arm F (cel+ZA)	Arm A (SOC G comparison)	Arm G	Arm A (SOC J comparison)	Arm J
Number of subjects	1184	593	592	593	622	312	311	957	960	987	989
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	521	265	270	252	294	139	146	322	326
From 65-84 years	663	328	322	341	328	173	164	635	633
85 years and over	0	0	0	0	0	0	1		1
Age continuous
Units:
	±	±	±	±	±	±	±	±	±	±	±
Gender categorical
Units: Subjects
Female	0	0	0	0	0	0	0	0	0
Male	1184	593	592	593	622	312	311	957	960

End points

Top of page

Reporting group title

Arm A (SOC for B,C,E comparisons)

Reporting group description

Reference patients for A vs B, C , E

Reporting group title

Arm B

Reporting group description

Zoledronic acid

Reporting group title

Arm C

Reporting group description

Docetaxel

Reporting group title

Arm E

Reporting group description

Zoledronic Acid and Docetaxel

Reporting group title

Arm A (SOC for D,F comparisons)

Reporting group description

Reference patients for A vs D, F

Reporting group title

Arm D

Reporting group description

Celecoxib

Reporting group title

Arm F

Reporting group description

Zoledronic Acid and Celecoxib

Reporting group title

Arm A (SOC - G comparison)

Reporting group description

Reference patients for arm G

Reporting group title

Arm G

Reporting group description

Abiraterone

Reporting group title

Arm A (SOC - J comparison)

Reporting group description

Reference patients for J comparison

Reporting group title

Arm J

Reporting group description

Enzalutamide and Abiraterone

Subject analysis set title

Arm A (SOC for B,C,E comparisons)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Reference patients (ABCE comparison)

Subject analysis set title

Arm B (ZA)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Experimental group, AB comparison

Subject analysis set title

Arm C (doce)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Arm A vs C

Subject analysis set title

Arm E (doce+ZA)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Docetaxel and Zoledronic acid

Subject analysis set title

Arm A (SOC for D,F comparisons)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Reference patients (ADF comparisons)

Subject analysis set title

Arm D (cel)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Arm A vs D

Subject analysis set title

Arm F (cel+ZA)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Arm A vs F

Subject analysis set title

Arm A (SOC G comparison)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Control arm for G comparison

Subject analysis set title

Arm G

Subject analysis set type

Intention-to-treat

Subject analysis set description

Abiraterone + prednisolone

Subject analysis set title

Arm A (SOC J comparison)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Reference patients for A vs J

Subject analysis set title

Arm J

Subject analysis set type

Intention-to-treat

Subject analysis set description

Enzalutamide and Abiraterone

Primary: Overall survival

Top of page

End point title

Overall survival

End point description

End point type

Primary

End point timeframe

Event driven analysis

End point values	Arm A (SOC for B,C,E comparisons)	Arm B (ZA)	Arm C (doce)	Arm E (doce+ZA)	Arm A (SOC for D,F comparisons)	Arm D (cel)	Arm F (cel+ZA)	Arm A (SOC G comparison)	Arm G	Arm A (SOC J comparison)	Arm J
Number of subjects analysed	1184	593	592	593	622	312	311	957	960	987	989
Units: Patients
Died	415	201	175	187	303	143	138	522	396	391	290

Zoledronic Acid vs SOC

Comparison groups

Arm A (SOC for B,C,E comparisons) v Arm B (ZA)

Number of subjects included in analysis

1777

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.45

Method

Logrank

Parameter type

Cox proportional hazard

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.11

Docetaxel vs SOC

Comparison groups

Arm A (SOC for B,C,E comparisons) v Arm C (doce)

Number of subjects included in analysis

1776

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

0.93

Docetaxel+Zoledronic Acid vs SOC

Comparison groups

Arm A (SOC for B,C,E comparisons) v Arm E (doce+ZA)

Number of subjects included in analysis

1777

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

0.97

Celecoxib vs SOC

Comparison groups

Arm D (cel) v Arm A (SOC for D,F comparisons)

Number of subjects included in analysis

934

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.847

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.2

Celecoxib + Zoledronic acid vs SOC

Comparison groups

Arm A (SOC for D,F comparisons) v Arm F (cel+ZA)

Number of subjects included in analysis

933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.13

Method

Logrank

Parameter type

Cox proportional hazard

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.05

Abiraterone vs SOC

Comparison groups

Arm A (SOC G comparison) v Arm G

Number of subjects included in analysis

1917

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

0.71

Enzalutamide and Abiraterone vs SOC

Comparison groups

Arm A (SOC J comparison) v Arm J

Number of subjects included in analysis

1976

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

0.74

Adverse events

Top of page

Timeframe for reporting adverse events

Events to March 4 2015 for A vs B,C,E comparisons Events to December 15 2015 for A vs D,F comparisons Events to July 3 2022 for A vs G/J comparisons

Assessment type

Systematic

Dictionary name

CTCAE

Dictionary version

4.0

Reporting group title

SOC (Arm A, ABCE comparison)

Reporting group description

Reference patients, Arm A, randomised between A,B,C,E

Reporting group title

ZA (Arm B)

Reporting group description

Experimental patients, AB comparison

Reporting group title

Doce (Arm C)

Reporting group description

Arm C docetaxel patients

Reporting group title

Doce+ZA (Arm E)

Reporting group description

Docetaxel plus Zoledronic acid

Reporting group title

SOC (Arm A, ADF comparison)

Reporting group description

Reference patients, Arm A, randomised between A,D,F

Reporting group title

Celecoxib (Arm D)

Reporting group description

Experimental arm, celecoxib comparison

Reporting group title

Celecoxib + ZA

Reporting group description

(Arm F)

Reporting group title

SOC (Arm A, G comparison)

Reporting group description

Reporting group title

Abiraterone (Arm G)

Reporting group description

Reporting group title

SOC (Arm A, J comparison)

Reporting group description

Reporting group title

Enzalutamide + Abiraterone (Arm J)

Reporting group description

Serious adverse events	SOC (Arm A, ABCE comparison)	ZA (Arm B)	Doce (Arm C)	Doce+ZA (Arm E)	SOC (Arm A, ADF comparison)	Celecoxib (Arm D)	Celecoxib + ZA	SOC (Arm A, G comparison)	Abiraterone (Arm G)	SOC (Arm A, J comparison)	Enzalutamide + Abiraterone (Arm J)
Total subjects affected by serious adverse events
subjects affected / exposed	117 / 1184 (9.88%)	80 / 593 (13.49%)	176 / 592 (29.73%)	209 / 593 (35.24%)	74 / 622 (11.90%)	40 / 312 (12.82%)	64 / 311 (20.58%)	144 / 957 (15.05%)	281 / 960 (29.27%)	156 / 987 (15.81%)	302 / 989 (30.54%)
number of deaths (all causes)	415	201	175	187	303	143	138	522	396	391	290
number of deaths resulting from adverse events	7	2	3	8	6	2	5	4	14	1	16
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	5 / 957 (0.52%)	3 / 960 (0.31%)	0 / 987 (0.00%)	2 / 989 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 5	0 / 4	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	1 / 1184 (0.08%)	0 / 593 (0.00%)	1 / 592 (0.17%)	0 / 593 (0.00%)	1 / 622 (0.16%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	5 / 989 (0.51%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	4 / 6
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
Hypotension
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	4 / 593 (0.67%)	0 / 622 (0.00%)	0 / 312 (0.00%)	2 / 311 (0.64%)	1 / 957 (0.10%)	2 / 960 (0.21%)	1 / 987 (0.10%)	4 / 989 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 5	0 / 0	0 / 0	0 / 2	0 / 1	0 / 1	0 / 1	1 / 4
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
Thrombosis
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	1 / 957 (0.10%)	4 / 960 (0.42%)	3 / 987 (0.30%)	6 / 989 (0.61%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 5	0 / 3	0 / 6
deaths 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
Vascular - other
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	1 / 957 (0.10%)	1 / 960 (0.10%)	0 / 987 (0.00%)	0 / 989 (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
deaths 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
Surgical and medical procedures
Surgical - other
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	0 / 989 (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
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
General disorders and administration site conditions
Fatigue
subjects affected / exposed	2 / 1184 (0.17%)	0 / 593 (0.00%)	1 / 592 (0.17%)	2 / 593 (0.34%)	1 / 622 (0.16%)	0 / 312 (0.00%)	0 / 311 (0.00%)	1 / 957 (0.10%)	1 / 960 (0.10%)	0 / 987 (0.00%)	1 / 989 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 0	1 / 1	1 / 2	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	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
Oedema
subjects affected / exposed	1 / 1184 (0.08%)	0 / 593 (0.00%)	4 / 592 (0.68%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	1 / 957 (0.10%)	2 / 960 (0.21%)	0 / 987 (0.00%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	1 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	1 / 2	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
Fever
subjects affected / exposed	3 / 1184 (0.25%)	2 / 593 (0.34%)	6 / 592 (1.01%)	17 / 593 (2.87%)	2 / 622 (0.32%)	0 / 312 (0.00%)	2 / 311 (0.64%)	4 / 957 (0.42%)	4 / 960 (0.42%)	4 / 987 (0.41%)	9 / 989 (0.91%)
occurrences causally related to treatment / all	0 / 3	0 / 2	5 / 6	5 / 18	0 / 2	0 / 0	0 / 2	0 / 4	0 / 4	0 / 4	1 / 15
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
Chest pain
subjects affected / exposed	0 / 1184 (0.00%)	1 / 593 (0.17%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	1 / 957 (0.10%)	1 / 960 (0.10%)	1 / 987 (0.10%)	2 / 989 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 2
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
Pain
subjects affected / exposed	2 / 1184 (0.17%)	0 / 593 (0.00%)	0 / 592 (0.00%)	1 / 593 (0.17%)	1 / 622 (0.16%)	0 / 312 (0.00%)	0 / 311 (0.00%)	1 / 957 (0.10%)	0 / 960 (0.00%)	0 / 987 (0.00%)	2 / 989 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
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
Headache
subjects affected / exposed	2 / 1184 (0.17%)	0 / 593 (0.00%)	0 / 592 (0.00%)	2 / 593 (0.34%)	2 / 622 (0.32%)	1 / 312 (0.32%)	1 / 311 (0.32%)	0 / 957 (0.00%)	2 / 960 (0.21%)	1 / 987 (0.10%)	2 / 989 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2	0 / 2	0 / 1	1 / 1	0 / 0	0 / 2	0 / 1	1 / 2
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
General - other
subjects affected / exposed	10 / 1184 (0.84%)	11 / 593 (1.85%)	18 / 592 (3.04%)	17 / 593 (2.87%)	8 / 622 (1.29%)	6 / 312 (1.92%)	4 / 311 (1.29%)	10 / 957 (1.04%)	27 / 960 (2.81%)	8 / 987 (0.81%)	16 / 989 (1.62%)
occurrences causally related to treatment / all	0 / 10	0 / 11	5 / 20	0 / 19	0 / 8	0 / 6	0 / 4	0 / 10	0 / 27	0 / 9	3 / 17
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0	0 / 5
Fall
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	1 / 957 (0.10%)	6 / 960 (0.63%)	3 / 987 (0.30%)	6 / 989 (0.61%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 6	0 / 3	0 / 6
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
Influenza like illness
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	1 / 989 (0.10%)
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
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
Oral candidiasis
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	0 / 989 (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
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
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 1184 (0.08%)	0 / 593 (0.00%)	8 / 592 (1.35%)	4 / 593 (0.67%)	1 / 622 (0.16%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	8 / 8	4 / 4	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
Social circumstances
Social - other
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	1 / 957 (0.10%)	0 / 960 (0.00%)	0 / 987 (0.00%)	0 / 989 (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
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
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	2 / 592 (0.34%)	1 / 593 (0.17%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	2 / 960 (0.21%)	1 / 987 (0.10%)	1 / 989 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	1 / 1	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
Dyspnoea
subjects affected / exposed	4 / 1184 (0.34%)	3 / 593 (0.51%)	5 / 592 (0.84%)	5 / 593 (0.84%)	2 / 622 (0.32%)	0 / 312 (0.00%)	3 / 311 (0.96%)	7 / 957 (0.73%)	11 / 960 (1.15%)	6 / 987 (0.61%)	5 / 989 (0.51%)
occurrences causally related to treatment / all	0 / 4	0 / 3	4 / 6	2 / 5	0 / 2	0 / 0	0 / 4	0 / 7	0 / 13	1 / 6	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Respiratory - other
subjects affected / exposed	14 / 1184 (1.18%)	10 / 593 (1.69%)	22 / 592 (3.72%)	22 / 593 (3.71%)	11 / 622 (1.77%)	7 / 312 (2.24%)	6 / 311 (1.93%)	15 / 957 (1.57%)	24 / 960 (2.50%)	9 / 987 (0.91%)	12 / 989 (1.21%)
occurrences causally related to treatment / all	0 / 15	0 / 10	8 / 23	5 / 23	0 / 12	0 / 7	0 / 6	0 / 17	0 / 28	0 / 9	0 / 14
deaths causally related to treatment / all	0 / 2	0 / 1	0 / 1	1 / 3	0 / 1	0 / 2	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	1 / 592 (0.17%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	0 / 989 (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
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
Cognitive disorder
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	1 / 312 (0.32%)	1 / 311 (0.32%)	1 / 957 (0.10%)	1 / 960 (0.10%)	0 / 987 (0.00%)	3 / 989 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 2	0 / 0	1 / 3
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
Psychiatric - other
subjects affected / exposed	1 / 1184 (0.08%)	1 / 593 (0.17%)	2 / 592 (0.34%)	0 / 593 (0.00%)	1 / 622 (0.16%)	0 / 312 (0.00%)	1 / 311 (0.32%)	0 / 957 (0.00%)	4 / 960 (0.42%)	0 / 987 (0.00%)	1 / 989 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 4	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	1 / 987 (0.10%)	1 / 989 (0.10%)
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	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
Investigations
Thrombocytopenia
subjects affected / exposed	1 / 1184 (0.08%)	0 / 593 (0.00%)	1 / 592 (0.17%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	1 / 957 (0.10%)	1 / 960 (0.10%)	0 / 987 (0.00%)	1 / 989 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	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
Investigations - other
subjects affected / exposed	2 / 1184 (0.17%)	1 / 593 (0.17%)	5 / 592 (0.84%)	11 / 593 (1.85%)	1 / 622 (0.16%)	1 / 312 (0.32%)	2 / 311 (0.64%)	1 / 957 (0.10%)	4 / 960 (0.42%)	0 / 987 (0.00%)	1 / 989 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 1	4 / 5	7 / 12	0 / 1	0 / 1	0 / 2	0 / 1	1 / 4	0 / 0	0 / 1
deaths 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
Bilirubin conjugated increased
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	1 / 989 (0.10%)
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
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
Aspartate aminotransferase increased
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	2 / 989 (0.20%)
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	2 / 2
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
Alanine aminotransferase increased
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	2 / 989 (0.20%)
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	2 / 2
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
Cardiac disorders
Myocardial infarction
subjects affected / exposed	7 / 1184 (0.59%)	4 / 593 (0.67%)	4 / 592 (0.68%)	5 / 593 (0.84%)	5 / 622 (0.80%)	2 / 312 (0.64%)	1 / 311 (0.32%)	7 / 957 (0.73%)	17 / 960 (1.77%)	14 / 987 (1.42%)	23 / 989 (2.33%)
occurrences causally related to treatment / all	0 / 7	0 / 4	1 / 4	0 / 5	0 / 5	0 / 2	0 / 1	0 / 7	1 / 17	0 / 14	4 / 25
deaths causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 2	0 / 1	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0	0 / 4
Arrhythmia
subjects affected / exposed	2 / 1184 (0.17%)	1 / 593 (0.17%)	2 / 592 (0.34%)	6 / 593 (1.01%)	0 / 622 (0.00%)	2 / 312 (0.64%)	0 / 311 (0.00%)	1 / 957 (0.10%)	2 / 960 (0.21%)	0 / 987 (0.00%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2	2 / 7	0 / 0	0 / 2	0 / 0	0 / 1	0 / 2	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
Heart failure
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	1 / 312 (0.32%)	0 / 311 (0.00%)	1 / 957 (0.10%)	1 / 960 (0.10%)	1 / 987 (0.10%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1	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
Cardiac - other
subjects affected / exposed	7 / 1184 (0.59%)	7 / 593 (1.18%)	10 / 592 (1.69%)	9 / 593 (1.52%)	3 / 622 (0.48%)	3 / 312 (0.96%)	6 / 311 (1.93%)	8 / 957 (0.84%)	31 / 960 (3.23%)	12 / 987 (1.22%)	24 / 989 (2.43%)
occurrences causally related to treatment / all	0 / 7	0 / 7	1 / 10	0 / 9	0 / 3	0 / 3	1 / 6	0 / 8	3 / 33	0 / 12	6 / 25
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 4
Chest pain
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	2 / 960 (0.21%)	0 / 987 (0.00%)	4 / 989 (0.40%)
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 / 4
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
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 1184 (0.00%)	2 / 593 (0.34%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	2 / 960 (0.21%)	0 / 987 (0.00%)	2 / 989 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 2
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
Nervous system - other
subjects affected / exposed	12 / 1184 (1.01%)	5 / 593 (0.84%)	7 / 592 (1.18%)	14 / 593 (2.36%)	8 / 622 (1.29%)	1 / 312 (0.32%)	6 / 311 (1.93%)	15 / 957 (1.57%)	23 / 960 (2.40%)	7 / 987 (0.71%)	18 / 989 (1.82%)
occurrences causally related to treatment / all	0 / 14	0 / 5	2 / 7	0 / 14	0 / 10	0 / 1	1 / 7	0 / 15	0 / 26	1 / 7	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 3	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	2 / 960 (0.21%)	1 / 987 (0.10%)	6 / 989 (0.61%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 1	3 / 7
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
Stroke
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	2 / 957 (0.21%)	1 / 960 (0.10%)	2 / 987 (0.20%)	7 / 989 (0.71%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 2	0 / 7
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
Transient ischaemic attack
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	1 / 989 (0.10%)
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
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
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	5 / 1184 (0.42%)	3 / 593 (0.51%)	2 / 592 (0.34%)	2 / 593 (0.34%)	1 / 622 (0.16%)	1 / 312 (0.32%)	3 / 311 (0.96%)	7 / 957 (0.73%)	6 / 960 (0.63%)	4 / 987 (0.41%)	4 / 989 (0.40%)
occurrences causally related to treatment / all	0 / 8	0 / 3	1 / 2	0 / 2	0 / 1	0 / 1	0 / 3	0 / 10	1 / 9	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	7 / 1184 (0.59%)	3 / 593 (0.51%)	77 / 592 (13.01%)	65 / 593 (10.96%)	4 / 622 (0.64%)	0 / 312 (0.00%)	2 / 311 (0.64%)	2 / 957 (0.21%)	3 / 960 (0.31%)	14 / 987 (1.42%)	9 / 989 (0.91%)
occurrences causally related to treatment / all	0 / 7	0 / 4	79 / 83	66 / 73	0 / 4	0 / 0	0 / 2	0 / 2	0 / 4	11 / 14	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	3 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	1 / 1184 (0.08%)	0 / 593 (0.00%)	3 / 592 (0.51%)	9 / 593 (1.52%)	1 / 622 (0.16%)	0 / 312 (0.00%)	1 / 311 (0.32%)	0 / 957 (0.00%)	1 / 960 (0.10%)	1 / 987 (0.10%)	3 / 989 (0.30%)
occurrences causally related to treatment / all	0 / 1	0 / 0	2 / 3	9 / 9	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1	2 / 3
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
Blood - other
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	1 / 989 (0.10%)
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 / 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
Ear and labyrinth disorders
ear - other
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	1 / 989 (0.10%)
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
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
Eye disorders
Eye - other
subjects affected / exposed	1 / 1184 (0.08%)	1 / 593 (0.17%)	2 / 592 (0.34%)	2 / 593 (0.34%)	1 / 622 (0.16%)	0 / 312 (0.00%)	1 / 311 (0.32%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	3 / 989 (0.30%)
occurrences causally related to treatment / all	0 / 1	0 / 1	1 / 2	0 / 2	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	1 / 3
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
Conjunctivitis
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	0 / 989 (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
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
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	4 / 1184 (0.34%)	4 / 593 (0.67%)	2 / 592 (0.34%)	7 / 593 (1.18%)	3 / 622 (0.48%)	1 / 312 (0.32%)	6 / 311 (1.93%)	8 / 957 (0.84%)	11 / 960 (1.15%)	4 / 987 (0.41%)	6 / 989 (0.61%)
occurrences causally related to treatment / all	0 / 4	0 / 4	2 / 2	0 / 7	0 / 3	1 / 1	0 / 6	0 / 8	0 / 12	0 / 5	0 / 8
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
Constipation
subjects affected / exposed	3 / 1184 (0.25%)	1 / 593 (0.17%)	3 / 592 (0.51%)	1 / 593 (0.17%)	3 / 622 (0.48%)	1 / 312 (0.32%)	1 / 311 (0.32%)	2 / 957 (0.21%)	2 / 960 (0.21%)	1 / 987 (0.10%)	3 / 989 (0.30%)
occurrences causally related to treatment / all	0 / 3	0 / 1	1 / 3	0 / 1	0 / 3	0 / 1	0 / 1	0 / 2	0 / 2	0 / 1	0 / 3
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
Diarrhoea
subjects affected / exposed	5 / 1184 (0.42%)	1 / 593 (0.17%)	8 / 592 (1.35%)	10 / 593 (1.69%)	4 / 622 (0.64%)	0 / 312 (0.00%)	3 / 311 (0.96%)	2 / 957 (0.21%)	12 / 960 (1.25%)	2 / 987 (0.20%)	6 / 989 (0.61%)
occurrences causally related to treatment / all	0 / 5	0 / 1	5 / 8	5 / 11	0 / 4	0 / 0	0 / 3	0 / 2	0 / 13	1 / 2	0 / 6
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
Nausea
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	2 / 592 (0.34%)	6 / 593 (1.01%)	0 / 622 (0.00%)	0 / 312 (0.00%)	1 / 311 (0.32%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	3 / 7	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	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
Vomiting
subjects affected / exposed	2 / 1184 (0.17%)	2 / 593 (0.34%)	3 / 592 (0.51%)	6 / 593 (1.01%)	2 / 622 (0.32%)	0 / 312 (0.00%)	0 / 311 (0.00%)	2 / 957 (0.21%)	6 / 960 (0.63%)	3 / 987 (0.30%)	5 / 989 (0.51%)
occurrences causally related to treatment / all	0 / 2	0 / 2	1 / 3	2 / 7	0 / 2	0 / 0	0 / 0	0 / 2	1 / 7	1 / 3	0 / 5
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
Stomatitis
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	1 / 592 (0.17%)	1 / 593 (0.17%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	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
Haemorrhage
subjects affected / exposed	2 / 1184 (0.17%)	1 / 593 (0.17%)	2 / 592 (0.34%)	5 / 593 (0.84%)	0 / 622 (0.00%)	1 / 312 (0.32%)	1 / 311 (0.32%)	7 / 957 (0.73%)	5 / 960 (0.52%)	6 / 987 (0.61%)	9 / 989 (0.91%)
occurrences causally related to treatment / all	0 / 6	0 / 1	0 / 5	0 / 5	0 / 0	1 / 1	0 / 1	0 / 12	0 / 5	0 / 6	0 / 10
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
Gastrointestinal - other
subjects affected / exposed	11 / 1184 (0.93%)	5 / 593 (0.84%)	12 / 592 (2.03%)	16 / 593 (2.70%)	5 / 622 (0.80%)	1 / 312 (0.32%)	7 / 311 (2.25%)	19 / 957 (1.99%)	28 / 960 (2.92%)	18 / 987 (1.82%)	17 / 989 (1.72%)
occurrences causally related to treatment / all	0 / 12	0 / 5	2 / 12	4 / 19	0 / 6	0 / 1	1 / 7	0 / 19	0 / 30	0 / 23	0 / 18
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
Dyspepsia
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	2 / 960 (0.21%)	0 / 987 (0.00%)	2 / 989 (0.20%)
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 / 2
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
Hepatobiliary disorders
Hepatobiliary - other
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	1 / 593 (0.17%)	0 / 622 (0.00%)	1 / 312 (0.32%)	0 / 311 (0.00%)	1 / 957 (0.10%)	0 / 960 (0.00%)	2 / 987 (0.20%)	1 / 989 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 3	0 / 0	0 / 2	0 / 1
deaths 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
Cholecystitis
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	2 / 960 (0.21%)	1 / 987 (0.10%)	1 / 989 (0.10%)
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 / 1	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
Skin and subcutaneous tissue disorders
Nail discolouration
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	1 / 592 (0.17%)	1 / 593 (0.17%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	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
Rash
subjects affected / exposed	0 / 1184 (0.00%)	1 / 593 (0.17%)	1 / 592 (0.17%)	2 / 593 (0.34%)	0 / 622 (0.00%)	2 / 312 (0.64%)	0 / 311 (0.00%)	1 / 957 (0.10%)	3 / 960 (0.31%)	2 / 987 (0.20%)	2 / 989 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	1 / 3	0 / 0	1 / 2	0 / 0	0 / 1	1 / 3	0 / 2	1 / 2
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
Skin - other
subjects affected / exposed	1 / 1184 (0.08%)	1 / 593 (0.17%)	5 / 592 (0.84%)	6 / 593 (1.01%)	1 / 622 (0.16%)	0 / 312 (0.00%)	2 / 311 (0.64%)	1 / 957 (0.10%)	11 / 960 (1.15%)	2 / 987 (0.20%)	4 / 989 (0.40%)
occurrences causally related to treatment / all	0 / 1	0 / 1	1 / 5	2 / 7	0 / 1	0 / 0	0 / 2	0 / 1	0 / 12	0 / 3	1 / 4
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
Skin infection
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	1 / 987 (0.10%)	4 / 989 (0.40%)
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 / 4
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
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	4 / 1184 (0.34%)	2 / 593 (0.34%)	0 / 592 (0.00%)	2 / 593 (0.34%)	2 / 622 (0.32%)	0 / 312 (0.00%)	2 / 311 (0.64%)	1 / 957 (0.10%)	6 / 960 (0.63%)	3 / 987 (0.30%)	6 / 989 (0.61%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 0	0 / 2	0 / 2	0 / 0	0 / 2	0 / 1	0 / 7	0 / 3	0 / 7
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Haematuria
subjects affected / exposed	2 / 1184 (0.17%)	2 / 593 (0.34%)	0 / 592 (0.00%)	3 / 593 (0.51%)	2 / 622 (0.32%)	0 / 312 (0.00%)	1 / 311 (0.32%)	7 / 957 (0.73%)	7 / 960 (0.73%)	4 / 987 (0.41%)	5 / 989 (0.51%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 4	0 / 2	0 / 0	0 / 1	0 / 13	1 / 11	0 / 4	0 / 5
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
Chronic kidney disease
subjects affected / exposed	4 / 1184 (0.34%)	3 / 593 (0.51%)	1 / 592 (0.17%)	3 / 593 (0.51%)	2 / 622 (0.32%)	0 / 312 (0.00%)	2 / 311 (0.64%)	4 / 957 (0.42%)	1 / 960 (0.10%)	0 / 987 (0.00%)	2 / 989 (0.20%)
occurrences causally related to treatment / all	0 / 4	0 / 3	0 / 1	0 / 3	0 / 2	0 / 0	0 / 2	0 / 4	0 / 1	0 / 0	1 / 2
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
Hepatic failure
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	1 / 312 (0.32%)	0 / 311 (0.00%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	2 / 989 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	1 / 1	0 / 0	2 / 2
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
Renal and urinary - other
subjects affected / exposed	18 / 1184 (1.52%)	9 / 593 (1.52%)	5 / 592 (0.84%)	8 / 593 (1.35%)	10 / 622 (1.61%)	5 / 312 (1.60%)	5 / 311 (1.61%)	15 / 957 (1.57%)	24 / 960 (2.50%)	9 / 987 (0.91%)	12 / 989 (1.21%)
occurrences causally related to treatment / all	0 / 20	0 / 9	0 / 5	0 / 8	0 / 12	0 / 5	0 / 6	0 / 17	0 / 28	0 / 9	0 / 14
deaths causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	2 / 960 (0.21%)	0 / 987 (0.00%)	2 / 989 (0.20%)
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 / 3
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
Urinary frequency
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	0 / 989 (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
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
Obstruction
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	5 / 957 (0.52%)	2 / 960 (0.21%)	10 / 987 (1.01%)	3 / 989 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 6	0 / 2	0 / 11	0 / 3
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
Musculoskeletal and connective tissue disorders
Bone pain
subjects affected / exposed	3 / 1184 (0.25%)	2 / 593 (0.34%)	3 / 592 (0.51%)	1 / 593 (0.17%)	3 / 622 (0.48%)	1 / 312 (0.32%)	0 / 311 (0.00%)	0 / 957 (0.00%)	4 / 960 (0.42%)	2 / 987 (0.20%)	1 / 989 (0.10%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 3	0 / 1	0 / 3	0 / 1	0 / 0	0 / 0	0 / 4	0 / 2	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
Arthralgia
subjects affected / exposed	1 / 1184 (0.08%)	1 / 593 (0.17%)	0 / 592 (0.00%)	1 / 593 (0.17%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	4 / 960 (0.42%)	1 / 987 (0.10%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 5	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
Musculoskeletal - other
subjects affected / exposed	13 / 1184 (1.10%)	15 / 593 (2.53%)	12 / 592 (2.03%)	38 / 593 (6.41%)	7 / 622 (1.13%)	6 / 312 (1.92%)	9 / 311 (2.89%)	8 / 957 (0.84%)	22 / 960 (2.29%)	11 / 987 (1.11%)	34 / 989 (3.44%)
occurrences causally related to treatment / all	0 / 13	10 / 15	3 / 13	20 / 41	0 / 7	0 / 6	4 / 9	0 / 8	0 / 28	0 / 14	0 / 36
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
Back pain
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	2 / 960 (0.21%)	2 / 987 (0.20%)	4 / 989 (0.40%)
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 / 2	0 / 4
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
Myalgia
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	1 / 989 (0.10%)
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
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
Infections and infestations
Urinary tract infection
subjects affected / exposed	5 / 1184 (0.42%)	2 / 593 (0.34%)	6 / 592 (1.01%)	4 / 593 (0.67%)	2 / 622 (0.32%)	1 / 312 (0.32%)	2 / 311 (0.64%)	8 / 957 (0.84%)	16 / 960 (1.67%)	9 / 987 (0.91%)	20 / 989 (2.02%)
occurrences causally related to treatment / all	0 / 6	0 / 2	2 / 6	0 / 5	0 / 2	0 / 1	0 / 2	0 / 9	1 / 18	0 / 9	1 / 24
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
Upper respiratory tract infection
subjects affected / exposed	1 / 1184 (0.08%)	0 / 593 (0.00%)	1 / 592 (0.17%)	1 / 593 (0.17%)	1 / 622 (0.16%)	1 / 312 (0.32%)	3 / 311 (0.96%)	0 / 957 (0.00%)	2 / 960 (0.21%)	0 / 987 (0.00%)	7 / 989 (0.71%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1	0 / 1	0 / 1	0 / 3	0 / 0	0 / 2	0 / 0	0 / 7
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Infections - other
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	6 / 960 (0.63%)	2 / 987 (0.20%)	5 / 989 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 7	0 / 2	0 / 5
deaths 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 / 1
Abdominal infection
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	2 / 989 (0.20%)
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 / 2
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
Lower respiratory tract infection
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	3 / 957 (0.31%)	26 / 960 (2.71%)	10 / 987 (1.01%)	21 / 989 (2.12%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	0 / 34	0 / 12	0 / 29
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 1
Sepsis
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	2 / 960 (0.21%)	0 / 987 (0.00%)	0 / 989 (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 / 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
Metabolism and nutrition disorders
Glucose tolerance decreased
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	1 / 592 (0.17%)	1 / 593 (0.17%)	0 / 622 (0.00%)	0 / 312 (0.00%)	1 / 311 (0.32%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	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
Hypokalaemia
subjects affected / exposed	1 / 1184 (0.08%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	1 / 311 (0.32%)	1 / 957 (0.10%)	5 / 960 (0.52%)	0 / 987 (0.00%)	4 / 989 (0.40%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	1 / 5	0 / 0	2 / 4
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
Anorexia nervosa
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	1 / 593 (0.17%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	0 / 989 (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
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
Hypocalcaemia
subjects affected / exposed	1 / 1184 (0.08%)	0 / 593 (0.00%)	1 / 592 (0.17%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	2 / 957 (0.21%)	1 / 960 (0.10%)	1 / 987 (0.10%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	1 / 1	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
Hypophosphataemia
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	1 / 592 (0.17%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	1 / 989 (0.10%)
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 / 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
Diabetes mellitus
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	1 / 592 (0.17%)	1 / 593 (0.17%)	0 / 622 (0.00%)	0 / 312 (0.00%)	1 / 311 (0.32%)	1 / 957 (0.10%)	0 / 960 (0.00%)	0 / 987 (0.00%)	0 / 989 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	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
Metabolism and nutrition - other
subjects affected / exposed	0 / 1184 (0.00%)	2 / 593 (0.34%)	1 / 592 (0.17%)	4 / 593 (0.67%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	1 / 960 (0.10%)	0 / 987 (0.00%)	4 / 989 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 8	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	1 / 4
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
Hyperkalaemia
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	0 / 957 (0.00%)	0 / 960 (0.00%)	0 / 987 (0.00%)	1 / 989 (0.10%)
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
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

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	SOC (Arm A, ABCE comparison)	ZA (Arm B)	Doce (Arm C)	Doce+ZA (Arm E)	SOC (Arm A, ADF comparison)	Celecoxib (Arm D)	Celecoxib + ZA	SOC (Arm A, G comparison)	Abiraterone (Arm G)	SOC (Arm A, J comparison)	Enzalutamide + Abiraterone (Arm J)
Total subjects affected by non serious adverse events
subjects affected / exposed	1152 / 1184 (97.30%)	579 / 593 (97.64%)	571 / 592 (96.45%)	560 / 593 (94.44%)	605 / 622 (97.27%)	292 / 312 (93.59%)	297 / 311 (95.50%)	946 / 957 (98.85%)	953 / 960 (99.27%)	974 / 987 (98.68%)	975 / 989 (98.58%)
Vascular disorders
Hypertension
subjects affected / exposed	84 / 1184 (7.09%)	50 / 593 (8.43%)	44 / 592 (7.43%)	30 / 593 (5.06%)	35 / 622 (5.63%)	39 / 312 (12.50%)	27 / 311 (8.68%)	180 / 957 (18.81%)	368 / 960 (38.33%)	190 / 987 (19.25%)	554 / 989 (56.02%)
occurrences all number	129	90	74	42	47	63	43	349	955	443	1864
Hot flush
subjects affected / exposed	968 / 1184 (81.76%)	462 / 593 (77.91%)	454 / 592 (76.69%)	442 / 593 (74.54%)	495 / 622 (79.58%)	229 / 312 (73.40%)	222 / 311 (71.38%)	819 / 957 (85.58%)	851 / 960 (88.65%)	863 / 987 (87.44%)	899 / 989 (90.90%)
occurrences all number	5324	2400	2425	2356	2877	1321	1268	5295	6524	5792	7236
General disorders and administration site conditions
Fever
subjects affected / exposed	29 / 1184 (2.45%)	38 / 593 (6.41%)	49 / 592 (8.28%)	70 / 593 (11.80%)	13 / 622 (2.09%)	6 / 312 (1.92%)	17 / 311 (5.47%)	35 / 957 (3.66%)	50 / 960 (5.21%)	48 / 987 (4.86%)	66 / 989 (6.67%)
occurrences all number	39	51	58	84	19	8	17	39	55	60	79
Fatigue
subjects affected / exposed	632 / 1184 (53.38%)	342 / 593 (57.67%)	431 / 592 (72.80%)	427 / 593 (72.01%)	333 / 622 (53.54%)	151 / 312 (48.40%)	165 / 311 (53.05%)	612 / 957 (63.95%)	706 / 960 (73.54%)	720 / 987 (72.95%)	870 / 989 (87.97%)
occurrences all number	1999	1144	1616	1607	1080	424	536	2441	3557	3132	5374
Oedema
subjects affected / exposed	164 / 1184 (13.85%)	72 / 593 (12.14%)	159 / 592 (26.86%)	142 / 593 (23.95%)	97 / 622 (15.59%)	55 / 312 (17.63%)	51 / 311 (16.40%)	172 / 957 (17.97%)	235 / 960 (24.48%)	237 / 987 (24.01%)	245 / 989 (24.77%)
occurrences all number	350	124	354	283	207	100	85	414	657	569	584
Influenza like illness
subjects affected / exposed	97 / 1184 (8.19%)	215 / 593 (36.26%)	87 / 592 (14.70%)	140 / 593 (23.61%)	63 / 622 (10.13%)	27 / 312 (8.65%)	74 / 311 (23.79%)	57 / 957 (5.96%)	106 / 960 (11.04%)	46 / 987 (4.66%)	79 / 989 (7.99%)
occurrences all number	125	363	119	210	84	36	136	66	133	53	85
Pain
subjects affected / exposed	363 / 1184 (30.66%)	240 / 593 (40.47%)	188 / 592 (31.76%)	234 / 593 (39.46%)	187 / 622 (30.06%)	90 / 312 (28.85%)	94 / 311 (30.23%)	285 / 957 (29.78%)	325 / 960 (33.85%)	232 / 987 (23.51%)	215 / 989 (21.74%)
occurrences all number	720	485	384	501	364	162	180	575	585	379	368
General - other
subjects affected / exposed	99 / 1184 (8.36%)	62 / 593 (10.46%)	86 / 592 (14.53%)	93 / 593 (15.68%)	70 / 622 (11.25%)	24 / 312 (7.69%)	14 / 311 (4.50%)	81 / 957 (8.46%)	123 / 960 (12.81%)	66 / 987 (6.69%)	120 / 989 (12.13%)
occurrences all number	121	79	108	132	82	24	17	109	189	98	159
Immune system disorders
Hypersensitivity
subjects affected / exposed	39 / 1184 (3.29%)	21 / 593 (3.54%)	58 / 592 (9.80%)	42 / 593 (7.08%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	35 / 957 (3.66%)	41 / 960 (4.27%)	28 / 987 (2.84%)	38 / 989 (3.84%)
occurrences all number	47	24	69	53	0	0	0	47	52	30	46
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	586 / 1184 (49.49%)	296 / 593 (49.92%)	277 / 592 (46.79%)	281 / 593 (47.39%)	308 / 622 (49.52%)	127 / 312 (40.71%)	135 / 311 (43.41%)	518 / 957 (54.13%)	555 / 960 (57.81%)	524 / 987 (53.09%)	591 / 989 (59.76%)
occurrences all number	3230	1587	1545	1628	1851	740	820	3040	3929	3227	4160
Gynaecomastia
subjects affected / exposed	84 / 1184 (7.09%)	38 / 593 (6.41%)	29 / 592 (4.90%)	37 / 593 (6.24%)	47 / 622 (7.56%)	19 / 312 (6.09%)	17 / 311 (5.47%)	170 / 957 (17.76%)	170 / 960 (17.71%)	264 / 987 (26.75%)	296 / 989 (29.93%)
occurrences all number	145	57	41	58	74	41	32	390	472	758	1021
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	129 / 1184 (10.90%)	56 / 593 (9.44%)	95 / 592 (16.05%)	79 / 593 (13.32%)	59 / 622 (9.49%)	19 / 312 (6.09%)	29 / 311 (9.32%)	155 / 957 (16.20%)	289 / 960 (30.10%)	226 / 987 (22.90%)	218 / 989 (22.04%)
occurrences all number	229	73	152	136	103	31	36	315	638	456	443
Dyspnoea
subjects affected / exposed	171 / 1184 (14.44%)	82 / 593 (13.83%)	122 / 592 (20.61%)	117 / 593 (19.73%)	82 / 622 (13.18%)	45 / 312 (14.42%)	38 / 311 (12.22%)	212 / 957 (22.15%)	306 / 960 (31.88%)	262 / 987 (26.55%)	320 / 989 (32.36%)
occurrences all number	362	154	256	253	169	99	72	546	920	703	945
Rhinitis
subjects affected / exposed	62 / 1184 (5.24%)	32 / 593 (5.40%)	41 / 592 (6.93%)	39 / 593 (6.58%)	38 / 622 (6.11%)	17 / 312 (5.45%)	21 / 311 (6.75%)	40 / 957 (4.18%)	73 / 960 (7.60%)	44 / 987 (4.46%)	67 / 989 (6.77%)
occurrences all number	102	55	71	61	65	24	39	65	112	61	105
Respiratory - other
subjects affected / exposed	95 / 1184 (8.02%)	58 / 593 (9.78%)	77 / 592 (13.01%)	72 / 593 (12.14%)	64 / 622 (10.29%)	26 / 312 (8.33%)	32 / 311 (10.29%)	66 / 957 (6.90%)	143 / 960 (14.90%)	62 / 987 (6.28%)	99 / 989 (10.01%)
occurrences all number	150	88	115	103	96	38	39	112	229	83	135
Psychiatric disorders
Insomnia
subjects affected / exposed	291 / 1184 (24.58%)	152 / 593 (25.63%)	189 / 592 (31.93%)	170 / 593 (28.67%)	154 / 622 (24.76%)	69 / 312 (22.12%)	78 / 311 (25.08%)	266 / 957 (27.80%)	336 / 960 (35.00%)	329 / 987 (33.33%)	385 / 989 (38.93%)
occurrences all number	784	362	457	416	389	142	197	780	1105	1051	1336
Anxiety
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	60 / 957 (6.27%)	103 / 960 (10.73%)	152 / 987 (15.40%)	209 / 989 (21.13%)
occurrences all number	0	0	0	0	0	0	0	98	172	340	533
Depression
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	54 / 957 (5.64%)	92 / 960 (9.58%)	143 / 987 (14.49%)	214 / 989 (21.64%)
occurrences all number	0	0	0	0	0	0	0	94	166	286	533
Libido decreased
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	38 / 957 (3.97%)	67 / 960 (6.98%)	104 / 987 (10.54%)	137 / 989 (13.85%)
occurrences all number	0	0	0	0	0	0	0	43	103	198	263
Psychiatric - other
subjects affected / exposed	195 / 1184 (16.47%)	79 / 593 (13.32%)	100 / 592 (16.89%)	95 / 593 (16.02%)	104 / 622 (16.72%)	48 / 312 (15.38%)	44 / 311 (14.15%)	180 / 957 (18.81%)	236 / 960 (24.58%)	147 / 987 (14.89%)	204 / 989 (20.63%)
occurrences all number	482	171	191	197	274	75	94	402	636	298	369
Investigations
Neutrophil count
subjects affected / exposed	46 / 1184 (3.89%)	25 / 593 (4.22%)	114 / 592 (19.26%)	111 / 593 (18.72%)	28 / 622 (4.50%)	11 / 312 (3.53%)	9 / 311 (2.89%)	48 / 957 (5.02%)	80 / 960 (8.33%)	77 / 987 (7.80%)	99 / 989 (10.01%)
occurrences all number	82	37	160	148	47	26	12	81	129	119	193
Alkaline phosphatase increased
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	28 / 957 (2.93%)	47 / 960 (4.90%)	100 / 987 (10.13%)	96 / 989 (9.71%)
occurrences all number	0	0	0	0	0	0	0	35	62	156	197
cholesterol high
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	28 / 957 (2.93%)	45 / 960 (4.69%)	45 / 987 (4.56%)	60 / 989 (6.07%)
occurrences all number	0	0	0	0	0	0	0	37	79	79	112
Investigations - other
subjects affected / exposed	297 / 1184 (25.08%)	161 / 593 (27.15%)	160 / 592 (27.03%)	153 / 593 (25.80%)	173 / 622 (27.81%)	83 / 312 (26.60%)	90 / 311 (28.94%)	323 / 957 (33.75%)	432 / 960 (45.00%)	305 / 987 (30.90%)	363 / 989 (36.70%)
occurrences all number	587	301	353	317	361	180	201	713	1311	626	866
Aspartate aminotransferase increased
subjects affected / exposed	32 / 1184 (2.70%)	17 / 593 (2.87%)	21 / 592 (3.55%)	22 / 593 (3.71%)	16 / 622 (2.57%)	7 / 312 (2.24%)	11 / 311 (3.54%)	34 / 957 (3.55%)	81 / 960 (8.44%)	38 / 987 (3.85%)	139 / 989 (14.05%)
occurrences all number	58	31	39	28	34	11	21	57	171	59	243
Alanine aminotransferase increased
subjects affected / exposed	110 / 1184 (9.29%)	55 / 593 (9.27%)	69 / 592 (11.66%)	63 / 593 (10.62%)	53 / 622 (8.52%)	29 / 312 (9.29%)	26 / 311 (8.36%)	145 / 957 (15.15%)	267 / 960 (27.81%)	170 / 987 (17.22%)	389 / 989 (39.33%)
occurrences all number	218	102	139	140	116	73	52	281	605	334	902
Platelet count decreased
subjects affected / exposed	28 / 1184 (2.36%)	21 / 593 (3.54%)	26 / 592 (4.39%)	37 / 593 (6.24%)	15 / 622 (2.41%)	11 / 312 (3.53%)	11 / 311 (3.54%)	44 / 957 (4.60%)	55 / 960 (5.73%)	58 / 987 (5.88%)	62 / 989 (6.27%)
occurrences all number	60	38	60	74	40	29	37	99	118	113	121
Weight increased
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	45 / 957 (4.70%)	60 / 960 (6.25%)	170 / 987 (17.22%)	159 / 989 (16.08%)
occurrences all number	0	0	0	0	0	0	0	54	90	269	254
Cardiac disorders
cardiac - other
subjects affected / exposed	60 / 1184 (5.07%)	24 / 593 (4.05%)	35 / 592 (5.91%)	24 / 593 (4.05%)	35 / 622 (5.63%)	18 / 312 (5.77%)	16 / 311 (5.14%)	64 / 957 (6.69%)	96 / 960 (10.00%)	35 / 987 (3.55%)	63 / 989 (6.37%)
occurrences all number	133	37	59	36	79	33	32	97	163	46	115
Arrhythmia
subjects affected / exposed	41 / 1184 (3.46%)	21 / 593 (3.54%)	21 / 592 (3.55%)	18 / 593 (3.04%)	20 / 622 (3.22%)	17 / 312 (5.45%)	15 / 311 (4.82%)	41 / 957 (4.28%)	68 / 960 (7.08%)	32 / 987 (3.24%)	63 / 989 (6.37%)
occurrences all number	63	40	30	28	32	35	26	61	132	47	108
Nervous system disorders
Dizziness
subjects affected / exposed	141 / 1184 (11.91%)	75 / 593 (12.65%)	88 / 592 (14.86%)	93 / 593 (15.68%)	90 / 622 (14.47%)	40 / 312 (12.82%)	37 / 311 (11.90%)	137 / 957 (14.32%)	190 / 960 (19.79%)	151 / 987 (15.30%)	253 / 989 (25.58%)
occurrences all number	252	152	141	158	169	69	65	215	389	312	476
Headache
subjects affected / exposed	161 / 1184 (13.60%)	86 / 593 (14.50%)	95 / 592 (16.05%)	98 / 593 (16.53%)	100 / 622 (16.08%)	35 / 312 (11.22%)	38 / 311 (12.22%)	120 / 957 (12.54%)	186 / 960 (19.38%)	139 / 987 (14.08%)	261 / 989 (26.39%)
occurrences all number	334	153	190	172	202	63	80	264	383	269	584
Nervous system - other
subjects affected / exposed	106 / 1184 (8.95%)	64 / 593 (10.79%)	235 / 592 (39.70%)	206 / 593 (34.74%)	61 / 622 (9.81%)	42 / 312 (13.46%)	52 / 311 (16.72%)	104 / 957 (10.87%)	158 / 960 (16.46%)	146 / 987 (14.79%)	211 / 989 (21.33%)
occurrences all number	163	97	597	449	96	68	81	180	307	235	412
Cognitive disorder
subjects affected / exposed	21 / 1184 (1.77%)	16 / 593 (2.70%)	10 / 592 (1.69%)	10 / 593 (1.69%)	12 / 622 (1.93%)	4 / 312 (1.28%)	4 / 311 (1.29%)	52 / 957 (5.43%)	73 / 960 (7.60%)	55 / 987 (5.57%)	187 / 989 (18.91%)
occurrences all number	26	21	12	16	15	6	8	95	142	84	377
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	322 / 1184 (27.20%)	212 / 593 (35.75%)	228 / 592 (38.51%)	252 / 593 (42.50%)	172 / 622 (27.65%)	78 / 312 (25.00%)	108 / 311 (34.73%)	385 / 957 (40.23%)	489 / 960 (50.94%)	456 / 987 (46.20%)	502 / 989 (50.76%)
occurrences all number	931	653	691	902	495	255	370	1300	1966	1559	1978
Eye disorders
Vision blurred
subjects affected / exposed	54 / 1184 (4.56%)	27 / 593 (4.55%)	44 / 592 (7.43%)	61 / 593 (10.29%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	45 / 957 (4.70%)	67 / 960 (6.98%)	56 / 987 (5.67%)	82 / 989 (8.29%)
occurrences all number	85	54	73	105	0	0	0	79	112	81	146
Eye - other
subjects affected / exposed	74 / 1184 (6.25%)	41 / 593 (6.91%)	91 / 592 (15.37%)	97 / 593 (16.36%)	50 / 622 (8.04%)	19 / 312 (6.09%)	25 / 311 (8.04%)	53 / 957 (5.54%)	98 / 960 (10.21%)	50 / 987 (5.07%)	98 / 989 (9.91%)
occurrences all number	113	67	152	175	74	30	39	83	166	83	178
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	160 / 1184 (13.51%)	76 / 593 (12.82%)	114 / 592 (19.26%)	127 / 593 (21.42%)	89 / 622 (14.31%)	60 / 312 (19.23%)	54 / 311 (17.36%)	142 / 957 (14.84%)	208 / 960 (21.67%)	163 / 987 (16.51%)	196 / 989 (19.82%)
occurrences all number	298	131	200	203	161	95	106	283	414	305	382
Constipation
subjects affected / exposed	218 / 1184 (18.41%)	147 / 593 (24.79%)	207 / 592 (34.97%)	212 / 593 (35.75%)	125 / 622 (20.10%)	46 / 312 (14.74%)	70 / 311 (22.51%)	259 / 957 (27.06%)	333 / 960 (34.69%)	317 / 987 (32.12%)	394 / 989 (39.84%)
occurrences all number	440	278	389	436	268	81	147	605	895	801	987
Diarrhoea
subjects affected / exposed	251 / 1184 (21.20%)	139 / 593 (23.44%)	247 / 592 (41.72%)	233 / 593 (39.29%)	134 / 622 (21.54%)	85 / 312 (27.24%)	77 / 311 (24.76%)	286 / 957 (29.89%)	337 / 960 (35.10%)	349 / 987 (35.36%)	419 / 989 (42.37%)
occurrences all number	495	250	499	451	274	143	133	637	726	823	954
Dyspepsia
subjects affected / exposed	155 / 1184 (13.09%)	76 / 593 (12.82%)	137 / 592 (23.14%)	125 / 593 (21.08%)	97 / 622 (15.59%)	67 / 312 (21.47%)	57 / 311 (18.33%)	120 / 957 (12.54%)	181 / 960 (18.85%)	141 / 987 (14.29%)	187 / 989 (18.91%)
occurrences all number	314	123	245	208	221	110	102	223	374	283	350
Flatulence
subjects affected / exposed	167 / 1184 (14.10%)	79 / 593 (13.32%)	88 / 592 (14.86%)	78 / 593 (13.15%)	105 / 622 (16.88%)	48 / 312 (15.38%)	43 / 311 (13.83%)	149 / 957 (15.57%)	163 / 960 (16.98%)	205 / 987 (20.77%)	248 / 989 (25.08%)
occurrences all number	395	160	158	132	252	89	105	377	357	413	588
Haemorrhage
subjects affected / exposed	90 / 1184 (7.60%)	36 / 593 (6.07%)	44 / 592 (7.43%)	46 / 593 (7.76%)	48 / 622 (7.72%)	15 / 312 (4.81%)	20 / 311 (6.43%)	79 / 957 (8.25%)	84 / 960 (8.75%)	77 / 987 (7.80%)	103 / 989 (10.41%)
occurrences all number	148	70	71	74	81	28	35	154	139	132	159
Nausea
subjects affected / exposed	128 / 1184 (10.81%)	77 / 593 (12.98%)	151 / 592 (25.51%)	152 / 593 (25.63%)	80 / 622 (12.86%)	43 / 312 (13.78%)	37 / 311 (11.90%)	112 / 957 (11.70%)	180 / 960 (18.75%)	154 / 987 (15.60%)	267 / 989 (27.00%)
occurrences all number	210	131	226	265	126	57	59	201	353	252	558
Vomiting
subjects affected / exposed	61 / 1184 (5.15%)	30 / 593 (5.06%)	57 / 592 (9.63%)	65 / 593 (10.96%)	41 / 622 (6.59%)	23 / 312 (7.37%)	24 / 311 (7.72%)	47 / 957 (4.91%)	94 / 960 (9.79%)	71 / 987 (7.19%)	113 / 989 (11.43%)
occurrences all number	81	39	73	88	52	25	35	63	130	98	154
Stomatitis
subjects affected / exposed	36 / 1184 (3.04%)	25 / 593 (4.22%)	153 / 592 (25.84%)	149 / 593 (25.13%)	22 / 622 (3.54%)	15 / 312 (4.81%)	18 / 311 (5.79%)	22 / 957 (2.30%)	35 / 960 (3.65%)	33 / 987 (3.34%)	35 / 989 (3.54%)
occurrences all number	57	31	210	216	32	17	26	30	59	41	39
Gastrointestinal - other
subjects affected / exposed	181 / 1184 (15.29%)	75 / 593 (12.65%)	156 / 592 (26.35%)	143 / 593 (24.11%)	97 / 622 (15.59%)	52 / 312 (16.67%)	40 / 311 (12.86%)	164 / 957 (17.14%)	230 / 960 (23.96%)	179 / 987 (18.14%)	236 / 989 (23.86%)
occurrences all number	294	108	260	268	168	74	64	290	384	299	424
Hepatobiliary disorders
Hepatic failure
subjects affected / exposed	65 / 1184 (5.49%)	35 / 593 (5.90%)	37 / 592 (6.25%)	44 / 593 (7.42%)	27 / 622 (4.34%)	27 / 312 (8.65%)	27 / 311 (8.68%)	53 / 957 (5.54%)	116 / 960 (12.08%)	41 / 987 (4.15%)	59 / 989 (5.97%)
occurrences all number	105	69	71	78	49	52	44	77	195	60	78
Skin and subcutaneous tissue disorders
Nail discolouration
subjects affected / exposed	61 / 1184 (5.15%)	37 / 593 (6.24%)	258 / 592 (43.58%)	194 / 593 (32.72%)	35 / 622 (5.63%)	16 / 312 (5.13%)	23 / 311 (7.40%)	53 / 957 (5.54%)	64 / 960 (6.67%)	66 / 987 (6.69%)	88 / 989 (8.90%)
occurrences all number	109	51	583	406	53	21	47	98	103	148	168
Rash
subjects affected / exposed	117 / 1184 (9.88%)	67 / 593 (11.30%)	73 / 592 (12.33%)	70 / 593 (11.80%)	70 / 622 (11.25%)	48 / 312 (15.38%)	41 / 311 (13.18%)	92 / 957 (9.61%)	158 / 960 (16.46%)	110 / 987 (11.14%)	124 / 989 (12.54%)
occurrences all number	199	91	104	116	126	77	67	167	262	166	213
Alopecia
subjects affected / exposed	7 / 1184 (0.59%)	2 / 593 (0.34%)	80 / 592 (13.51%)	69 / 593 (11.64%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	8 / 957 (0.84%)	6 / 960 (0.63%)	22 / 987 (2.23%)	32 / 989 (3.24%)
occurrences all number	7	3	136	118	0	0	0	12	16	30	50
Skin - other
subjects affected / exposed	202 / 1184 (17.06%)	89 / 593 (15.01%)	238 / 592 (40.20%)	216 / 593 (36.42%)	112 / 622 (18.01%)	37 / 312 (11.86%)	51 / 311 (16.40%)	171 / 957 (17.87%)	259 / 960 (26.98%)	146 / 987 (14.79%)	238 / 989 (24.06%)
occurrences all number	318	136	449	400	176	67	69	297	489	262	444
Renal and urinary disorders
Urinary frequency
subjects affected / exposed	605 / 1184 (51.10%)	308 / 593 (51.94%)	307 / 592 (51.86%)	279 / 593 (47.05%)	310 / 622 (49.84%)	146 / 312 (46.79%)	138 / 311 (44.37%)	637 / 957 (66.56%)	666 / 960 (69.38%)	731 / 987 (74.06%)	733 / 989 (74.12%)
occurrences all number	2125	957	969	934	1130	514	438	2706	3221	3435	3869
Acute kidney injury
subjects affected / exposed	92 / 1184 (7.77%)	71 / 593 (11.97%)	49 / 592 (8.28%)	75 / 593 (12.65%)	51 / 622 (8.20%)	25 / 312 (8.01%)	57 / 311 (18.33%)	27 / 957 (2.82%)	37 / 960 (3.85%)	48 / 987 (4.86%)	49 / 989 (4.95%)
occurrences all number	183	232	95	201	101	47	171	35	48	75	76
Haematuria
subjects affected / exposed	57 / 1184 (4.81%)	23 / 593 (3.88%)	22 / 592 (3.72%)	35 / 593 (5.90%)	40 / 622 (6.43%)	21 / 312 (6.73%)	14 / 311 (4.50%)	78 / 957 (8.15%)	96 / 960 (10.00%)	83 / 987 (8.41%)	78 / 989 (7.89%)
occurrences all number	86	34	30	44	60	30	16	110	129	122	117
Chronic kidney disease
subjects affected / exposed	92 / 1184 (7.77%)	71 / 593 (11.97%)	49 / 592 (8.28%)	75 / 593 (12.65%)	51 / 622 (8.20%)	25 / 312 (8.01%)	57 / 311 (18.33%)	102 / 957 (10.66%)	114 / 960 (11.88%)	84 / 987 (8.51%)	96 / 989 (9.71%)
occurrences all number	183	232	95	201	101	47	171	233	339	187	245
Renal - other
subjects affected / exposed	189 / 1184 (15.96%)	88 / 593 (14.84%)	97 / 592 (16.39%)	94 / 593 (15.85%)	102 / 622 (16.40%)	55 / 312 (17.63%)	39 / 311 (12.54%)	219 / 957 (22.88%)	196 / 960 (20.42%)	240 / 987 (24.32%)	235 / 989 (23.76%)
occurrences all number	301	132	154	150	157	90	60	387	362	472	435
Urinary urgency
subjects affected / exposed	0 / 1184 (0.00%)	0 / 593 (0.00%)	0 / 592 (0.00%)	0 / 593 (0.00%)	0 / 622 (0.00%)	0 / 312 (0.00%)	0 / 311 (0.00%)	111 / 957 (11.60%)	118 / 960 (12.29%)	281 / 987 (28.47%)	324 / 989 (32.76%)
occurrences all number	0	0	0	0	0	0	0	164	204	605	774
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	144 / 1184 (12.16%)	69 / 593 (11.64%)	64 / 592 (10.81%)	64 / 593 (10.79%)	87 / 622 (13.99%)	28 / 312 (8.97%)	35 / 311 (11.25%)	89 / 957 (9.30%)	137 / 960 (14.27%)	230 / 987 (23.30%)	267 / 989 (27.00%)
occurrences all number	246	109	107	97	154	45	71	125	215	467	561
Myalgia
subjects affected / exposed	184 / 1184 (15.54%)	109 / 593 (18.38%)	133 / 592 (22.47%)	141 / 593 (23.78%)	101 / 622 (16.24%)	34 / 312 (10.90%)	53 / 311 (17.04%)	170 / 957 (17.76%)	208 / 960 (21.67%)	206 / 987 (20.87%)	300 / 989 (30.33%)
occurrences all number	316	186	226	265	158	60	99	340	378	414	598
Arthralgia
subjects affected / exposed	303 / 1184 (25.59%)	189 / 593 (31.87%)	202 / 592 (34.12%)	214 / 593 (36.09%)	182 / 622 (29.26%)	87 / 312 (27.88%)	94 / 311 (30.23%)	263 / 957 (27.48%)	330 / 960 (34.38%)	334 / 987 (33.84%)	401 / 989 (40.55%)
occurrences all number	787	426	513	525	495	220	270	614	842	813	957
Bone pain
subjects affected / exposed	436 / 1184 (36.82%)	235 / 593 (39.63%)	190 / 592 (32.09%)	232 / 593 (39.12%)	249 / 622 (40.03%)	114 / 312 (36.54%)	119 / 311 (38.26%)	350 / 957 (36.57%)	346 / 960 (36.04%)	354 / 987 (35.87%)	358 / 989 (36.20%)
occurrences all number	920	531	441	517	564	240	300	683	721	674	811
Musculoskeletal - other
subjects affected / exposed	437 / 1184 (36.91%)	245 / 593 (41.32%)	247 / 592 (41.72%)	275 / 593 (46.37%)	254 / 622 (40.84%)	102 / 312 (32.69%)	117 / 311 (37.62%)	355 / 957 (37.10%)	416 / 960 (43.33%)	292 / 987 (29.58%)	343 / 989 (34.68%)
occurrences all number	922	546	549	617	559	183	228	742	1025	568	741
Infections and infestations
Urinary tract infection
subjects affected / exposed	94 / 1184 (7.94%)	57 / 593 (9.61%)	81 / 592 (13.68%)	83 / 593 (14.00%)	52 / 622 (8.36%)	27 / 312 (8.65%)	34 / 311 (10.93%)	90 / 957 (9.40%)	97 / 960 (10.10%)	90 / 987 (9.12%)	98 / 989 (9.91%)
occurrences all number	119	73	108	104	64	30	39	130	147	114	162
Sinusitis
subjects affected / exposed	37 / 1184 (3.13%)	21 / 593 (3.54%)	21 / 592 (3.55%)	20 / 593 (3.37%)	27 / 622 (4.34%)	12 / 312 (3.85%)	12 / 311 (3.86%)	24 / 957 (2.51%)	36 / 960 (3.75%)	21 / 987 (2.13%)	41 / 989 (4.15%)
occurrences all number	63	29	32	28	52	23	34	39	59	27	58
Upper respiratory tract infection
subjects affected / exposed	116 / 1184 (9.80%)	66 / 593 (11.13%)	97 / 592 (16.39%)	97 / 593 (16.36%)	61 / 622 (9.81%)	30 / 312 (9.62%)	36 / 311 (11.58%)	94 / 957 (9.82%)	159 / 960 (16.56%)	102 / 987 (10.33%)	141 / 989 (14.26%)
occurrences all number	157	85	132	128	79	36	44	125	237	140	191
Metabolism and nutrition disorders
Hypocalcaemia
subjects affected / exposed	39 / 1184 (3.29%)	64 / 593 (10.79%)	32 / 592 (5.41%)	57 / 593 (9.61%)	26 / 622 (4.18%)	16 / 312 (5.13%)	25 / 311 (8.04%)	35 / 957 (3.66%)	69 / 960 (7.19%)	37 / 987 (3.75%)	54 / 989 (5.46%)
occurrences all number	55	98	42	91	42	23	34	42	96	39	61
Anorexia nervosa
subjects affected / exposed	91 / 1184 (7.69%)	49 / 593 (8.26%)	73 / 592 (12.33%)	74 / 593 (12.48%)	56 / 622 (9.00%)	32 / 312 (10.26%)	35 / 311 (11.25%)	79 / 957 (8.25%)	110 / 960 (11.46%)	114 / 987 (11.55%)	182 / 989 (18.40%)
occurrences all number	120	78	85	118	79	40	47	122	189	186	354
Glucose tolerance decreased
subjects affected / exposed	37 / 1184 (3.13%)	21 / 593 (3.54%)	29 / 592 (4.90%)	30 / 593 (5.06%)	20 / 622 (3.22%)	13 / 312 (4.17%)	10 / 311 (3.22%)	59 / 957 (6.17%)	110 / 960 (11.46%)	79 / 987 (8.00%)	88 / 989 (8.90%)
occurrences all number	49	50	53	67	32	34	15	138	310	185	258
Metabolism - other
subjects affected / exposed	104 / 1184 (8.78%)	29 / 593 (4.89%)	46 / 592 (7.77%)	56 / 593 (9.44%)	45 / 622 (7.23%)	24 / 312 (7.69%)	13 / 311 (4.18%)	117 / 957 (12.23%)	124 / 960 (12.92%)	82 / 987 (8.31%)	115 / 989 (11.63%)
occurrences all number	152	44	56	73	73	42	16	179	236	145	186
Hypokalaemia
subjects affected / exposed	16 / 1184 (1.35%)	16 / 593 (2.70%)	20 / 592 (3.38%)	20 / 593 (3.37%)	5 / 622 (0.80%)	3 / 312 (0.96%)	6 / 311 (1.93%)	30 / 957 (3.13%)	129 / 960 (13.44%)	40 / 987 (4.05%)	142 / 989 (14.36%)
occurrences all number	17	19	29	28	6	4	11	32	234	64	247

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical Trial Results:
Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy