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Clinical Trial Results:
A Phase 3, Multicenter, Open-label, Randomized Study of SGI-110 versus Treatment Choice (TC) in Adults with Previously Untreated Acute Myeloid Leukemia (AML) Who Are Not Considered Candidates for Intensive Remission Induction Chemotherapy

Summary
EudraCT number	2014-001233-89
Trial protocol	IT SE BE HU DE GB NL FI CZ AT ES PL FR DK
Global end of trial date	17 Jun 2019

Results information
Results version number	v2(current)
This version publication date	06 Jan 2021
First version publication date	29 Jun 2020
Other versions	v1
Version creation reason	New data added to full data set Updating record following final database lock.

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

SGI-110-04

ISRCTN number

-

US NCT number

NCT02348489

WHO universal trial number (UTN)

-

Sponsor organisation name

Astex Pharmaceuticals, Inc.

Sponsor organisation address

4420 Rosewood Drive, Suite 200, Pleasanton, United States, 94588

Public contact

Clinical trial info SGI-110-04, Astex Pharmaceuticals, Inc., SGI-110-04@astx.com

Scientific contact

Clinical trial info SGI-110-04, Astex Pharmaceuticals, Inc., SGI-110-04@astx.com

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

Analysis stage

Final

Date of interim/final analysis

01 Jul 2019

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

17 Jun 2019

Was the trial ended prematurely?

No

Main objective of the trial

To assess and compare efficacy (complete response [CR] rate) and overall survival (OS) between SGI-110 and TC (treatment choice) in adults with previously untreated AML who are not considered candidates for intensive remission induction chemotherapy.

Protection of trial subjects

The study was conducted in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, US Title 21 CFR Parts 11, 50, 54, 56, and 312, EU Clinical Trials Directive and its successor, local regulatory requirements, the principles enunciated in the Declaration of Helsinki, and all human clinical research regulations in countries where the study was conducted.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

19 Mar 2015

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy

Long term follow-up duration

4 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 43

Country: Number of subjects enrolled

Sweden: 7

Country: Number of subjects enrolled

Taiwan: 23

Country: Number of subjects enrolled

United Kingdom: 9

Country: Number of subjects enrolled

United States: 125

Country: Number of subjects enrolled

Australia: 27

Country: Number of subjects enrolled

Austria: 11

Country: Number of subjects enrolled

Belgium: 19

Country: Number of subjects enrolled

Bulgaria: 14

Country: Number of subjects enrolled

Canada: 40

Country: Number of subjects enrolled

Czech Republic: 34

Country: Number of subjects enrolled

Denmark: 8

Country: Number of subjects enrolled

Finland: 8

Country: Number of subjects enrolled

France: 99

Country: Number of subjects enrolled

Germany: 42

Country: Number of subjects enrolled

Hungary: 30

Country: Number of subjects enrolled

Italy: 88

Country: Number of subjects enrolled

Japan: 61

Country: Number of subjects enrolled

Korea, Republic of: 56

Country: Number of subjects enrolled

Netherlands: 2

Country: Number of subjects enrolled

Poland: 46

Country: Number of subjects enrolled

Romania: 4

Country: Number of subjects enrolled

Russian Federation: 14

Country: Number of subjects enrolled

Serbia: 5

Worldwide total number of subjects

815

EEA total number of subjects

464

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

24

From 65 to 84 years

733

85 years and over

58

Subject disposition

Top of page

Recruitment details

The screening period was 19 March 2015 (first subject signed Informed Consent Form; ICF) to 25 November 2016 (last subject signed ICF), and the enrollment period was 23 March 2015 (first subject randomized) to 29 November 2016 (last subject randomized). Last visit for the last subject was 17 June 2019.

Screening details

A total of 949 subjects were assessed for study inclusion. Of these, 134 subjects failed screening assessments and 815 subjects were randomized. For efficacy analysis, median follow-up was 766 days (25.5 months), lower quartile follow-up was 671 days (22.4 months), and upper quartile follow-up was 896 days (29.9 months).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

SGI-110 (Guadecitabine)

Arm description

Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.

Arm type

Experimental

Investigational medicinal product name

Guadecitabine

Investigational medicinal product code

Other name

SGI-110

Pharmaceutical forms

Powder for concentrate for solution for injection/infusion

Routes of administration

Subcutaneous use

Dosage and administration details

Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.

Treatment Choice

Arm description

One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.

Arm type

Experimental

Investigational medicinal product name

Cytarabine, decitabine, or azacitidine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection, Powder for concentrate for solution for injection/infusion

Routes of administration

Intravenous use, Subcutaneous use

Dosage and administration details

One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.

Number of subjects in period 1	SGI-110 (Guadecitabine)	Treatment Choice
Started	408	407
Completed	55	40
Not completed	353	367
Consent withdrawn by subject	14	27
Death	336	335
Lost to follow-up	3	5

Baseline characteristics

Top of page

Reporting group title

SGI-110 (Guadecitabine)

Reporting group description

Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.

Reporting group title

Treatment Choice

Reporting group description

One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.

Reporting group values	SGI-110 (Guadecitabine)	Treatment Choice	Total
Number of subjects	408	407	815
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	75.9 ( 6.2 )	75.9 ( 5.8 )	-
Gender categorical
Units: Subjects
Female	177	165	342
Male	231	242	473

End points

Top of page

Reporting group title

SGI-110 (Guadecitabine)

Reporting group description

Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.

Reporting group title

Treatment Choice

Reporting group description

One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.

Primary: Number of Subjects With a Complete Response (CR)

Top of page

End point title

Number of Subjects With a Complete Response (CR)

End point description

Calculated as the number of subjects with a best response of CR divided by the total number of subjects included in the efficacy analysis. Response was assessed based on International Working Group 2003 acute myeloid leukemia (AML) response criteria by a blinded independent pathologist.

End point type

Primary

End point timeframe

Median follow-up of 25.5 months

End point values	SGI-110 (Guadecitabine)	Treatment Choice
Number of subjects analysed	408	407
Units: Number
Subjects	79	71

Difference in Complete Response

Statistical analysis description

The complete response rate was compared between the treatment groups using a Cochran Mantel-Haenszel (CMH) test at an alpha level of 0.04 stratified to adjust for stratification factors used at randomization: age (<75 or >= 75), Eastern Cooperative Oncology Group (ECOG) performance status (0-1, 2-3), study center region (North America, Europe, Rest of World), and secondary AML (secondary to MDS or other antecedent hematologic disorder) or poor-risk cytogenetics (Yes, No/Unknown).

Comparison groups

Treatment Choice v SGI-110 (Guadecitabine)

Number of subjects included in analysis

815

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.482

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in response rate (%)

Point estimate

1.92

Confidence interval

level

96%

sides

2-sided

lower limit

-3.67

upper limit

7.5

Primary: Overall Survival

Top of page

End point title

Overall Survival

End point description

Survival time was defined as the number of days from the day the subject was randomly assigned to study treatment to the date of death, regardless of cause, based on Kaplan-Meier estimates.

End point type

Primary

End point timeframe

At 676 death events

End point values	SGI-110 (Guadecitabine)	Treatment Choice
Number of subjects analysed	408	407
Units: Days
median (confidence interval 95%)	213 (187 to 255)	254 (223 to 282)

Overall Survival Comparison

Statistical analysis description

Overall survival curves were estimated using Kaplan-Meier method and compared between the treatment groups using a 2-sided stratification log-rank test, stratified by the same factors used at randomization: age (<75 or >= 75), Eastern Cooperative Oncology Group (ECOG) performance status (0-1, 2-3), study center region (North America, Europe, Rest of World), and secondary AML (secondary to MDS or other antecedent hematologic disorder) or poor-risk cytogenetics (Yes, No/Unknown).

Comparison groups

SGI-110 (Guadecitabine) v Treatment Choice

Number of subjects included in analysis

815

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7328

Method

Stratified log-rank

Parameter type

Hazard ratio (HR)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.14

Secondary: Composite Complete Response Rate (CRc)

Top of page

End point title

Composite Complete Response Rate (CRc)

End point description

CRc rate was calculated as the number of subjects with a best response of CR, complete response with incomplete platelet recovery (CRp), or complete response with incomplete blood count recovery (CRi) divided by the total number of subjects included in the efficacy analysis.

End point type

Secondary

End point timeframe

Median follow-up of 25.5 months

End point values	SGI-110 (Guadecitabine)	Treatment Choice
Number of subjects analysed	408	407
Units: Percent
number (not applicable)
Percent	22.8	22.4

No statistical analyses for this end point

Secondary: Number of Days Alive and Out of the Hospital (NDAOH)

Top of page

End point title

Number of Days Alive and Out of the Hospital (NDAOH)

End point description

Duration of each hospital stay in days was calculated as the date of discharge minus date of admission. The Number of Days Alive and Out of the Hospital [up to 180 days] was calculated as: NDAOH = 180 - total duration of all hospital stays within 180 days from the first treatment - number of death days before Day 180. For subjects who were lost to follow-up within 6 months, the NDAOH was calculated conservatively assuming that the subject would have died the day after the last contact day.

End point type

Secondary

End point timeframe

Up to Month 6 (180 days)

End point values	SGI-110 (Guadecitabine)	Treatment Choice
Number of subjects analysed	408	407
Units: Days
arithmetic mean (standard deviation)	98.1 ( 63.60 )	105.7 ( 63.58 )

No statistical analyses for this end point

Secondary: Progression-free Survival (PFS)

Top of page

End point title

Progression-free Survival (PFS)

End point description

Progression-free survival was defined as the number of days from randomization to the earliest date of investigator's assessment of disease progression, subject receiving an alternative anti-leukemia therapy (including haematopoietic cell transplant), or relapse by peripheral blood (PB) assessment or blinded bone marrow (BM) assessment, whichever occurred first, or death, regardless of cause, based on Kaplan-Meier estimates.

End point type

Secondary

End point timeframe

Median follow-up of 25.5 months

End point values	SGI-110 (Guadecitabine)	Treatment Choice
Number of subjects analysed	408	407
Units: Days
median (confidence interval 95%)	159 (136 to 178)	166 (148 to 179)

No statistical analyses for this end point

Secondary: Number of Red Blood Cell or Platelet Transfusions

Top of page

End point title

Number of Red Blood Cell or Platelet Transfusions

End point description

The total number of red blood cells (RBCs) transfused or, separately, the total number of platelets transfused up to the 6-month time point for each subject was counted from the date of randomisation to Day 180, the date of last contact, or date of death, whichever occurred earlier. One RBC or platelet transfusion was defined as one unit, and a single bag of RBCs or platelets was considered one unit.

End point type

Secondary

End point timeframe

Up to Month 6

End point values	SGI-110 (Guadecitabine)	Treatment Choice
Number of subjects analysed	408	407
Units: Transfusions
arithmetic mean (standard deviation)
Red blood cell transfusions	16.2 ( 11.84 )	15.6 ( 13.02 )
Platelet transfusions	12.5 ( 18.78 )	14.4 ( 39.10 )

No statistical analyses for this end point

Secondary: Change in Health-related Quality of Life (QOL) Scores from Baseline: EQ-5D-5L

Top of page

End point title

Change in Health-related Quality of Life (QOL) Scores from Baseline: EQ-5D-5L

End point description

EuroQol 5-level 5-dimension (EQ-5D-5L) descriptive scores were collected for each subject for a minimum of 6 months, unless the subject died or withdrew consent. Scores within each dimension for EQ-5D (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) were calculated using counts and proportions. This study used the 5-level EQ-5D version, which consists of 5 levels of problems (where Level 1 is no problems and Level 5 indicates extreme problems).

End point type

Secondary

End point timeframe

Baseline to Month 6

End point values	SGI-110 (Guadecitabine)	Treatment Choice
Number of subjects analysed	408 ^[1]	407 ^[2]
Units: Score on a scale
arithmetic mean (standard deviation)
Baseline	0.7767 ( 0.2160 )	0.7663 ( 0.2291 )
Month 6	0.8252 ( 0.1825 )	0.8240 ( 0.1948 )
Change from baseline	-0.0023 ( 0.1830 )	0.0112 ( 0.2325 )

Notes
[1] - Baseline = 391 subjects; Month 6 = 180 subjects; Change from Baseline = 177 subjects
[2] - Baseline = 378 subjects; Month 6 = 183 subjects; Change from Baseline = 178 subjects

No statistical analyses for this end point

Secondary: Change in Health-related Quality of Life (QOL) scores from baseline: EQ-VAS

Top of page

End point title

Change in Health-related Quality of Life (QOL) scores from baseline: EQ-VAS

End point description

EuroQol-Visual Analogue Scale (EQ-VAS) descriptive scores were collected for each subject for a minimum of 6 months, unless the subject died or withdrew consent. A vertical 20-cm scale for EQ-VAS was used where the lowest value of 0 was labeled "the worst health you can imagine" and the top value of 100 was labeled "the best health you can imagine." Mean change in scores from baseline are summarised.

End point type

Secondary

End point timeframe

Baseline to Month 6

End point values	SGI-110 (Guadecitabine)	Treatment Choice
Number of subjects analysed	408 ^[3]	407 ^[4]
Units: Score on a scale
arithmetic mean (standard deviation)
Baseline	64.64 ( 21.69 )	63.58 ( 21.05 )
Month 6	72.76 ( 18.61 )	71.72 ( 18.88 )
Change from baseline	3.28 ( 19.35 )	3.67 ( 22.16 )

Notes
[3] - Baseline = 391 subjects; Month 6 = 180 subjects; Change from Baseline = 177 subjects
[4] - Baseline = 377 subjects; Month 6 = 183 subjects; Change from Baseline = 178 subjects

No statistical analyses for this end point

Secondary: Duration of CR

Top of page

End point title

Duration of CR

End point description

Duration of CR (in number of days, based on Kaplan-Meier estimates) was calculated from the first time a CR was observed to the time of relapse, defined as the earliest time point whereby BM assessment or PB assessment indicated relapse/disease progression due to reappearance of leukemic blasts in PB or ≥ 5% leukemic blasts in BM.

End point type

Secondary

End point timeframe

Median follow-up of 25.5 months

End point values	SGI-110 (Guadecitabine)	Treatment Choice
Number of subjects analysed	408	407
Units: Days
median (confidence interval 95%)	217 (175 to 261)	231 (182 to 289)

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Median (range) duration of treatment was 5 cycles (1-42) for SGI-110 and 5 cycles (1-37) for Treatment Choice.

Adverse event reporting additional description

Treatment-emergent adverse events were defined as events that first occurred or worsened after the first dose of study treatment given on Cycle 1 Day 1 until 30 days after the last dose of study treatment or the start of an alternative anti-leukemia treatment, whichever occurred first.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

SGI-110 (Guadecitabine)

Reporting group description

Guadecitabine 60 mg/m^2 was administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles. Safety population (randomized participants who received study treatment) was analyzed for TEAEs.

Reporting group title

Treatment Choice

Reporting group description

One of the following treatment regimens was administered: 20 mg cytarabine subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days. Safety population (randomized participants who received study treatment) was analyzed for TEAEs.

Serious adverse events	SGI-110 (Guadecitabine)	Treatment Choice
Total subjects affected by serious adverse events
subjects affected / exposed	327 / 401 (81.55%)	297 / 392 (75.77%)
number of deaths (all causes)	341	344
number of deaths resulting from adverse events	117	120
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bile duct cancer
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Biliary neoplasm
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Central nervous system leukaemia
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chloroma
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endometrial cancer metastatic
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Kaposi's sarcoma
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung adenocarcinoma
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Metastatic squamous cell carcinoma
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Squamous cell carcinoma
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transitional cell carcinoma
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tumour associated fever
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Aortic aneurysm
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic dissection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Artery dissection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Circulatory collapse
subjects affected / exposed	5 / 401 (1.25%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	0 / 5	1 / 4
deaths causally related to treatment / all	0 / 5	0 / 3
Deep vein thrombosis
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematoma
subjects affected / exposed	3 / 401 (0.75%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 3	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hypotension
subjects affected / exposed	2 / 401 (0.50%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	1 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Iliac artery embolism
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Leriche syndrome
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Lupus vasculitis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Phlebitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Shock
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Shock haemorrhagic
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Thrombophlebitis
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Venous thrombosis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	2 / 401 (0.50%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 2
Catheter site erythema
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chest pain
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Death
subjects affected / exposed	5 / 401 (1.25%)	5 / 392 (1.28%)
occurrences causally related to treatment / all	0 / 5	0 / 5
deaths causally related to treatment / all	0 / 5	0 / 5
Device related thrombosis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Discomfort
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gait disturbance
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	9 / 401 (2.24%)	10 / 392 (2.55%)
occurrences causally related to treatment / all	4 / 9	0 / 10
deaths causally related to treatment / all	1 / 3	0 / 5
Impaired healing
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injection site reaction
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Malaise
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	5 / 401 (1.25%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	0 / 5	0 / 4
deaths causally related to treatment / all	0 / 3	0 / 3
Non-cardiac chest pain
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	16 / 401 (3.99%)	13 / 392 (3.32%)
occurrences causally related to treatment / all	3 / 19	2 / 14
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden cardiac death
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Sudden death
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 2
Systemic inflammatory response syndrome
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute respiratory distress syndrome
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	2 / 401 (0.50%)	6 / 392 (1.53%)
occurrences causally related to treatment / all	0 / 2	1 / 6
deaths causally related to treatment / all	0 / 1	1 / 3
Aspiration
subjects affected / exposed	1 / 401 (0.25%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	3 / 401 (0.75%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Laryngeal inflammation
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Laryngeal oedema
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Organising pneumonia
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oropharyngeal pain
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	6 / 401 (1.50%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	2 / 7	1 / 3
deaths causally related to treatment / all	0 / 1	0 / 0
Pleuritic pain
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	3 / 401 (0.75%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Pulmonary alveolar haemorrhage
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Pulmonary mass
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	5 / 401 (1.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Respiratory distress
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Respiratory failure
subjects affected / exposed	5 / 401 (1.25%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 3	0 / 1
Stridor
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary haemorrhage
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Psychiatric disorders
Confusional state
subjects affected / exposed	4 / 401 (1.00%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Delirium
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Personality change
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Product issues
Device dislocation
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Blood bilirubin increased
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
C-reactive protein increased
subjects affected / exposed	3 / 401 (0.75%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	1 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza A virus test positive
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Allergic transfusion reaction
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Contusion
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fall
subjects affected / exposed	1 / 401 (0.25%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fibula fracture
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fracture
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemolytic transfusion reaction
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Head injury
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	1 / 401 (0.25%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Splenic rupture
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subarachnoid haematoma
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Subdural haemorrhage
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transfusion reaction
subjects affected / exposed	4 / 401 (1.00%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Traumatic lung injury
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	1 / 1
Joint dislocation
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	3 / 401 (0.75%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Acute myocardial infarction
subjects affected / exposed	3 / 401 (0.75%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	0 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Angina pectoris
subjects affected / exposed	3 / 401 (0.75%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	5 / 401 (1.25%)	6 / 392 (1.53%)
occurrences causally related to treatment / all	0 / 5	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial tachycardia
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	3 / 401 (0.75%)	9 / 392 (2.30%)
occurrences causally related to treatment / all	0 / 3	1 / 9
deaths causally related to treatment / all	0 / 2	1 / 8
Cardiac failure
subjects affected / exposed	8 / 401 (2.00%)	10 / 392 (2.55%)
occurrences causally related to treatment / all	0 / 8	0 / 11
deaths causally related to treatment / all	0 / 5	0 / 3
Cardiac failure acute
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiac failure chronic
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiac failure congestive
subjects affected / exposed	4 / 401 (1.00%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	1 / 7	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiac tamponade
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	1 / 401 (0.25%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 3
Cardiogenic shock
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiopulmonary failure
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 1
Cardiorenal syndrome
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiovascular insufficiency
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Coronary artery stenosis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 401 (0.25%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Pericardial effusion
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sinus node dysfunction
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Supraventricular tachycardia
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Cerebral haemorrhage
subjects affected / exposed	1 / 401 (0.25%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 2
Cerebrovascular accident
subjects affected / exposed	6 / 401 (1.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 6	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0
Depressed level of consciousness
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Epilepsy
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Facial paralysis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	1 / 401 (0.25%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 4
Haemorrhagic stroke
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Headache
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intracranial haematoma
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Lethargy
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorder
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peroneal nerve palsy
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Presyncope
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Seizure
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	2 / 401 (0.50%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	0 / 2	1 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	1 / 401 (0.25%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vocal cord paralysis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Agranulocytosis
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anaemia
subjects affected / exposed	16 / 401 (3.99%)	10 / 392 (2.55%)
occurrences causally related to treatment / all	4 / 20	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Disseminated intravascular coagulation
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Febrile bone marrow aplasia
subjects affected / exposed	3 / 401 (0.75%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	2 / 3	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	101 / 401 (25.19%)	88 / 392 (22.45%)
occurrences causally related to treatment / all	72 / 147	46 / 138
deaths causally related to treatment / all	1 / 1	1 / 5
Haemorrhagic diathesis
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Histiocytosis haematophagic
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Leukocytosis
subjects affected / exposed	6 / 401 (1.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 7	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0
Lymphadenopathy
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphadenopathy mediastinal
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Monoclonal B-cell lymphocytosis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	2 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	2 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Splenic infarction
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	15 / 401 (3.74%)	5 / 392 (1.28%)
occurrences causally related to treatment / all	7 / 15	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Mastoid disorder
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden hearing loss
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vertigo
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	4 / 401 (1.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	2 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Anal fissure
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anal fistula
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	3 / 401 (0.75%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis ischaemic
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	8 / 401 (2.00%)	7 / 392 (1.79%)
occurrences causally related to treatment / all	1 / 9	7 / 10
deaths causally related to treatment / all	0 / 1	0 / 0
Diverticular perforation
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulum
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspepsia
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enteritis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Faecaloma
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus paralytic
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Incarcerated inguinal hernia
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Intussusception
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Melaena
subjects affected / exposed	3 / 401 (0.75%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Mesenteric artery thrombosis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenic colitis
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumatosis intestinalis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Proctalgia
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	2 / 401 (0.50%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Small intestinal haemorrhage
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Stomatitis
subjects affected / exposed	3 / 401 (0.75%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	2 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth disorder
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 2	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gallbladder obstruction
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis acute
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic hepatitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Jaundice cholestatic
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Portal vein thrombosis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Angioedema
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eczema
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypersensitivity vasculitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyoderma gangrenosum
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rash generalised
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rash maculo-papular
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin disorder
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin ulcer
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Toxic skin eruption
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	11 / 401 (2.74%)	15 / 392 (3.83%)
occurrences causally related to treatment / all	1 / 11	4 / 16
deaths causally related to treatment / all	0 / 1	0 / 1
Chronic kidney disease
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cystitis haemorrhagic
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematuria
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Renal colic
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal failure
subjects affected / exposed	4 / 401 (1.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ureterolithiasis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Diabetes insipidus
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Inappropriate antidiuretic hormone secretion
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bone pain
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bursitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Joint effusion
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Muscle atrophy
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Muscle haemorrhage
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal pain
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Neck pain
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Pain in extremity
subjects affected / exposed	1 / 401 (0.25%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal pain
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Shoulder deformity
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Abdominal wall abscess
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess intestinal
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	3 / 401 (0.75%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aspergillus infection
subjects affected / exposed	3 / 401 (0.75%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	2 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 401 (0.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	7 / 401 (1.75%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	3 / 8	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bacteroides bacteraemia
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	6 / 401 (1.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	1 / 6	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchopulmonary aspergillosis
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchopulmonary aspergillosis allergic
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Campylobacter gastroenteritis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	3 / 401 (0.75%)	6 / 392 (1.53%)
occurrences causally related to treatment / all	2 / 4	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis orbital
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Cellulitis staphylococcal
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium colitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	4 / 401 (1.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	1 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	4 / 401 (1.00%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	2 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cystitis
subjects affected / exposed	3 / 401 (0.75%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dermo-hypodermitis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Device related infection
subjects affected / exposed	4 / 401 (1.00%)	7 / 392 (1.79%)
occurrences causally related to treatment / all	0 / 4	2 / 8
deaths causally related to treatment / all	0 / 0	1 / 1
Device related sepsis
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	4 / 401 (1.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 6	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Encephalomyelitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocarditis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterobacter infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Epiglottitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia bacteraemia
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Eye infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gingivitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
H1N1 influenza
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haematoma infection
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatosplenic abscess
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes simplex
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster oticus
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infection
subjects affected / exposed	6 / 401 (1.50%)	5 / 392 (1.28%)
occurrences causally related to treatment / all	2 / 6	2 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Infectious colitis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	6 / 401 (1.50%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	1 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Injection site abscess
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injection site cellulitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injection site infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Kidney infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Liver abscess
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Localised infection
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mastoiditis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mucormycosis
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 1
Muscle abscess
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenic infection
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Osteomyelitis
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis media
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis media acute
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Parotitis
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pathogen resistance
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Periorbital cellulitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Periumbilical abscess
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 2	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Pneumonia
subjects affected / exposed	117 / 401 (29.18%)	79 / 392 (20.15%)
occurrences causally related to treatment / all	41 / 147	24 / 102
deaths causally related to treatment / all	4 / 20	3 / 23
Pneumonia cytomegaloviral
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia influenzal
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia legionella
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural cellulitis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pseudomembranous colitis
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pseudomonal sepsis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pseudomonas infection
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulpitis dental
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	2 / 401 (0.50%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal abscess
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Scrotal infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	62 / 401 (15.46%)	44 / 392 (11.22%)
occurrences causally related to treatment / all	18 / 83	14 / 58
deaths causally related to treatment / all	4 / 26	4 / 21
Septic shock
subjects affected / exposed	16 / 401 (3.99%)	17 / 392 (4.34%)
occurrences causally related to treatment / all	6 / 17	5 / 19
deaths causally related to treatment / all	3 / 8	1 / 6
Septic vasculitis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 401 (0.00%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	0 / 0	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Sinusitis fungal
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Soft tissue infection
subjects affected / exposed	3 / 401 (0.75%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal sepsis
subjects affected / exposed	2 / 401 (0.50%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	0 / 2	1 / 3
deaths causally related to treatment / all	0 / 1	0 / 0
Streptococcal bacteraemia
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Systemic candida
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Systemic infection
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth infection
subjects affected / exposed	2 / 401 (0.50%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tuberculosis pleurisy
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	4 / 401 (1.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urethritis
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	14 / 401 (3.49%)	10 / 392 (2.55%)
occurrences causally related to treatment / all	2 / 16	2 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection enterococcal
subjects affected / exposed	3 / 401 (0.75%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection staphylococcal
subjects affected / exposed	1 / 401 (0.25%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	3 / 401 (0.75%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Wound infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Wound infection staphylococcal
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis pseudomonas
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Klebsiella infection
subjects affected / exposed	3 / 401 (0.75%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia pseudomonal
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin infection
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	2 / 401 (0.50%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dehydration
subjects affected / exposed	2 / 401 (0.50%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	0 / 2	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	0 / 401 (0.00%)	1 / 392 (0.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	1 / 401 (0.25%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	1 / 401 (0.25%)	0 / 392 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	2 / 401 (0.50%)	4 / 392 (1.02%)
occurrences causally related to treatment / all	1 / 2	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 401 (0.25%)	3 / 392 (0.77%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Tumour lysis syndrome
subjects affected / exposed	5 / 401 (1.25%)	2 / 392 (0.51%)
occurrences causally related to treatment / all	1 / 5	2 / 2
deaths causally related to treatment / all	0 / 2	0 / 0

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

Non-serious adverse events	SGI-110 (Guadecitabine)	Treatment Choice
Total subjects affected by non serious adverse events
subjects affected / exposed	379 / 401 (94.51%)	371 / 392 (94.64%)
Vascular disorders
Haematoma
subjects affected / exposed	25 / 401 (6.23%)	19 / 392 (4.85%)
occurrences all number	33	29
Hypertension
subjects affected / exposed	28 / 401 (6.98%)	25 / 392 (6.38%)
occurrences all number	42	37
Hypotension
subjects affected / exposed	31 / 401 (7.73%)	31 / 392 (7.91%)
occurrences all number	40	37
General disorders and administration site conditions
Asthenia
subjects affected / exposed	61 / 401 (15.21%)	55 / 392 (14.03%)
occurrences all number	102	81
Fatigue
subjects affected / exposed	63 / 401 (15.71%)	50 / 392 (12.76%)
occurrences all number	97	74
Injection site reaction
subjects affected / exposed	73 / 401 (18.20%)	48 / 392 (12.24%)
occurrences all number	148	75
Oedema peripheral
subjects affected / exposed	95 / 401 (23.69%)	78 / 392 (19.90%)
occurrences all number	125	108
Pyrexia
subjects affected / exposed	89 / 401 (22.19%)	110 / 392 (28.06%)
occurrences all number	155	176
Pain
subjects affected / exposed	21 / 401 (5.24%)	14 / 392 (3.57%)
occurrences all number	22	14
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	79 / 401 (19.70%)	66 / 392 (16.84%)
occurrences all number	100	83
Dyspnoea
subjects affected / exposed	63 / 401 (15.71%)	51 / 392 (13.01%)
occurrences all number	83	60
Epistaxis
subjects affected / exposed	53 / 401 (13.22%)	36 / 392 (9.18%)
occurrences all number	71	51
Oropharyngeal pain
subjects affected / exposed	22 / 401 (5.49%)	23 / 392 (5.87%)
occurrences all number	29	27
Pleural effusion
subjects affected / exposed	21 / 401 (5.24%)	13 / 392 (3.32%)
occurrences all number	23	13
Psychiatric disorders
Anxiety
subjects affected / exposed	23 / 401 (5.74%)	22 / 392 (5.61%)
occurrences all number	23	24
Depression
subjects affected / exposed	14 / 401 (3.49%)	21 / 392 (5.36%)
occurrences all number	15	21
Insomnia
subjects affected / exposed	38 / 401 (9.48%)	45 / 392 (11.48%)
occurrences all number	52	56
Investigations
Weight decreased
subjects affected / exposed	35 / 401 (8.73%)	25 / 392 (6.38%)
occurrences all number	47	28
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	20 / 401 (4.99%)	22 / 392 (5.61%)
occurrences all number	23	27
Fall
subjects affected / exposed	34 / 401 (8.48%)	29 / 392 (7.40%)
occurrences all number	43	37
Nervous system disorders
Dizziness
subjects affected / exposed	36 / 401 (8.98%)	42 / 392 (10.71%)
occurrences all number	47	56
Headache
subjects affected / exposed	32 / 401 (7.98%)	38 / 392 (9.69%)
occurrences all number	44	53
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	88 / 401 (21.95%)	78 / 392 (19.90%)
occurrences all number	211	201
Febrile neutropenia
subjects affected / exposed	66 / 401 (16.46%)	40 / 392 (10.20%)
occurrences all number	103	57
Leukopenia
subjects affected / exposed	37 / 401 (9.23%)	33 / 392 (8.42%)
occurrences all number	120	124
Neutropenia
subjects affected / exposed	115 / 401 (28.68%)	88 / 392 (22.45%)
occurrences all number	319	233
Thrombocytopenia
subjects affected / exposed	116 / 401 (28.93%)	101 / 392 (25.77%)
occurrences all number	380	313
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	30 / 401 (7.48%)	46 / 392 (11.73%)
occurrences all number	43	50
Abdominal pain upper
subjects affected / exposed	21 / 401 (5.24%)	15 / 392 (3.83%)
occurrences all number	25	16
Constipation
subjects affected / exposed	125 / 401 (31.17%)	114 / 392 (29.08%)
occurrences all number	166	168
Diarrhoea
subjects affected / exposed	122 / 401 (30.42%)	83 / 392 (21.17%)
occurrences all number	169	116
Haemorrhoids
subjects affected / exposed	24 / 401 (5.99%)	19 / 392 (4.85%)
occurrences all number	28	24
Nausea
subjects affected / exposed	91 / 401 (22.69%)	108 / 392 (27.55%)
occurrences all number	141	150
Stomatitis
subjects affected / exposed	46 / 401 (11.47%)	38 / 392 (9.69%)
occurrences all number	59	44
Vomiting
subjects affected / exposed	58 / 401 (14.46%)	66 / 392 (16.84%)
occurrences all number	80	82
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	21 / 401 (5.24%)	17 / 392 (4.34%)
occurrences all number	21	20
Pruritus
subjects affected / exposed	22 / 401 (5.49%)	26 / 392 (6.63%)
occurrences all number	28	32
Rash
subjects affected / exposed	41 / 401 (10.22%)	28 / 392 (7.14%)
occurrences all number	55	33
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	23 / 401 (5.74%)	16 / 392 (4.08%)
occurrences all number	24	17
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	24 / 401 (5.99%)	35 / 392 (8.93%)
occurrences all number	28	39
Back pain
subjects affected / exposed	34 / 401 (8.48%)	36 / 392 (9.18%)
occurrences all number	43	43
Pain in extremity
subjects affected / exposed	40 / 401 (9.98%)	33 / 392 (8.42%)
occurrences all number	51	43
Musculoskeletal pain
subjects affected / exposed	17 / 401 (4.24%)	20 / 392 (5.10%)
occurrences all number	20	22
Infections and infestations
Bronchitis
subjects affected / exposed	22 / 401 (5.49%)	13 / 392 (3.32%)
occurrences all number	30	15
Cellulitis
subjects affected / exposed	29 / 401 (7.23%)	22 / 392 (5.61%)
occurrences all number	37	25
Nasopharyngitis
subjects affected / exposed	18 / 401 (4.49%)	20 / 392 (5.10%)
occurrences all number	27	21
Oral candidiasis
subjects affected / exposed	23 / 401 (5.74%)	17 / 392 (4.34%)
occurrences all number	27	21
Oral herpes
subjects affected / exposed	31 / 401 (7.73%)	20 / 392 (5.10%)
occurrences all number	36	21
Pneumonia
subjects affected / exposed	54 / 401 (13.47%)	31 / 392 (7.91%)
occurrences all number	64	34
Upper respiratory tract infection
subjects affected / exposed	22 / 401 (5.49%)	20 / 392 (5.10%)
occurrences all number	34	28
Urinary tract infection
subjects affected / exposed	33 / 401 (8.23%)	28 / 392 (7.14%)
occurrences all number	46	39
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	89 / 401 (22.19%)	62 / 392 (15.82%)
occurrences all number	116	80
Hyperkalaemia
subjects affected / exposed	24 / 401 (5.99%)	13 / 392 (3.32%)
occurrences all number	33	19
Hypoalbuminaemia
subjects affected / exposed	26 / 401 (6.48%)	23 / 392 (5.87%)
occurrences all number	36	43
Hypocalcaemia
subjects affected / exposed	25 / 401 (6.23%)	18 / 392 (4.59%)
occurrences all number	30	29
Hypokalaemia
subjects affected / exposed	96 / 401 (23.94%)	77 / 392 (19.64%)
occurrences all number	173	128
Hypomagnesaemia
subjects affected / exposed	31 / 401 (7.73%)	27 / 392 (6.89%)
occurrences all number	50	36

More information

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Were there any global substantial amendments to the protocol? Yes

06 Mar 2015

Amendment 1 incorporates changes required by the Voluntary Harmonisation Procedure (VHP) assessment of the protocol after clinical trial application in Europe and sponsor administrative changes.

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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