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Clinical Trial Results:
An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)

Summary
EudraCT number	2014-003630-23
Trial protocol	ES DE NL BE IE CZ AT PL HU FI GR RO IT
Global end of trial date	25 Oct 2024

Results information
Results version number	v1(current)
This version publication date	06 Nov 2025
First version publication date	06 Nov 2025
Other versions

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

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Trial information

Top of page

Sponsor protocol code

CA209-227

ISRCTN number

US NCT number

NCT02477826

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chaussée de la Hulpe 185, Brussels, Belgium,

Public contact

Global Submission Management, Clinical Trials, Bristol-Myers Squibb International Corporation, mg-gsm-ct@bms.com

Scientific contact

Global Submission Management, Clinical Trials, Bristol-Myers Squibb International Corporation, mg-gsm-ct@bms.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

28 Oct 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

25 Oct 2024

Global end of trial reached?

Yes

Global end of trial date

25 Oct 2024

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to show that Nivolumab, or Nivolumab plus Ipilimumab, or Nivolumab plus Platinum-Doublet Chemotherapy improves progression free survival and/or overall survival compared with chemotherapy in patients with advanced lung cancer.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Aug 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 102

Country: Number of subjects enrolled

Australia: 105

Country: Number of subjects enrolled

Austria: 9

Country: Number of subjects enrolled

Belgium: 28

Country: Number of subjects enrolled

Brazil: 67

Country: Number of subjects enrolled

Canada: 65

Country: Number of subjects enrolled

Switzerland: 28

Country: Number of subjects enrolled

Chile: 69

Country: Number of subjects enrolled

China: 350

Country: Number of subjects enrolled

Colombia: 26

Country: Number of subjects enrolled

Czechia: 21

Country: Number of subjects enrolled

Germany: 61

Country: Number of subjects enrolled

Spain: 157

Country: Number of subjects enrolled

Finland: 13

Country: Number of subjects enrolled

France: 192

Country: Number of subjects enrolled

United Kingdom: 69

Country: Number of subjects enrolled

Greece: 48

Country: Number of subjects enrolled

Hungary: 24

Country: Number of subjects enrolled

Ireland: 25

Country: Number of subjects enrolled

Israel: 21

Country: Number of subjects enrolled

Italy: 83

Country: Number of subjects enrolled

Japan: 269

Country: Number of subjects enrolled

Korea, Republic of: 130

Country: Number of subjects enrolled

Lebanon: 8

Country: Number of subjects enrolled

Mexico: 62

Country: Number of subjects enrolled

Netherlands: 32

Country: Number of subjects enrolled

Peru: 21

Country: Number of subjects enrolled

Poland: 161

Country: Number of subjects enrolled

Romania: 236

Country: Number of subjects enrolled

Russian Federation: 54

Country: Number of subjects enrolled

Taiwan: 32

Country: Number of subjects enrolled

United States: 171

Country: Number of subjects enrolled

South Africa: 8

Worldwide total number of subjects

2747

EEA total number of subjects

1090

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1488

From 65 to 84 years

1253

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Participants were enrolled in 33 countries.

Period 1 title

Pre-Treatment

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 1-Arm B: Nivo + Ipi

Arm description

Participants with PD-L1 positive status Non Small Cell Lung Cancer received nivolumab 3 mg/kg IV over 30 minutes Q2W + ipilimumab 1 mg/kg over 30minutes every 6 weeks (Q6W) given for up to 24 months in the absence of disease progression or unacceptable toxicity.

Arm type

Experimental

Investigational medicinal product name

No Treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Route of administration not applicable

Dosage and administration details

No Treatment

Part 1-Arm A: Nivolumab

Arm description

Participants with PD-L1 positive status Non Small Cell Lung Cancer received nivolumab 240 mg intravenously (IV) over 30 minutes every 2 weeks (Q2W) given for up to 24months in the absence of disease progression or unacceptable toxicity.

Arm type

Experimental

Investigational medicinal product name

No Treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Route of administration not applicable

Dosage and administration details

No Treatment

Part 1-Arm C: Chemotherapy

Arm description

Participants with PD-L1 positive status Non Small Cell Lung Cancer received histology-based platinum-doublet chemotherapy IV in3-week cycles for a maximum of 4 cycles or until disease progression or unacceptable toxicity (whichever comes first). For participants with NSQ histology, pemetrexed maintenance was allowed until disease progression or unacceptable toxicity after 4 cycles of chemotherapy.

Arm type

Active comparator

Investigational medicinal product name

No Treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Route of administration not applicable

Dosage and administration details

No Treatment

Part 1-Arm D: Nivo + Ipi

Arm description

Participants with PD-L1 negative status Non Small Cell Lung Cancer received nivolumab 3 mg/kg IV over 30 minutes Q2W + ipilimumab 1 mg/kg over 30minutes Q6W given for up to 24 months in the absence of disease progression or unacceptable toxicity.

Arm type

Experimental

Investigational medicinal product name

No Treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Route of administration not applicable

Dosage and administration details

No Treatment

Part 1-Arm G: Nivo + Chemo

Arm description

Participants with PD-L1 negative status Non Small Cell Lung Cancer received nivolumab 360 mg IV over 30 minutes combined with platinum-doublet chemotherapy administered IV every 3 weeks for a maximum of 4 cycles. Participants who have not experienced disease progression were to receive nivolumab 360 mg every 3weeks until the progression of disease, discontinuation due to toxicity, or up to 24 months (whichever comes first). For subjects with NSQ histology, pemetrexed maintenance was allowed until disease progression or unacceptable toxicity after 4 cycles of chemotherapy.

Arm type

Experimental

Investigational medicinal product name

No Treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Route of administration not applicable

Dosage and administration details

No Treatment

Part 1-Arm F: Chemotherapy

Arm description

Participants with PD-L1 negative status Non Small Cell Lung Cancer received histology-based platinum-doublet chemotherapy IV in 3-week cycles for a maximum of 4 cycles or until disease progression or unacceptable toxicity (whichever comes first). For participants with NSQ histology, pemetrexed maintenance was allowed until disease progression or unacceptable toxicity after 4 cycles of chemotherapy.

Arm type

Active comparator

Investigational medicinal product name

No Treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Route of administration not applicable

Dosage and administration details

No Treatment

Part 2 - Arm H: Nivolumab + Chemotherapy

Arm description

Chemotherapy-naive participants with stage IV or recurrent NSCLC irrespective of PD-L1 expressing levels received nivolumab 360 mg IV over 30 minutes combined with platinum-doublet chemotherapy administered IV every 3 weeks for a maximum of 4 cycles. Participants who have not experienced disease progression were to receive nivolumab 360 mg every 3weeks until the progression of disease, discontinuation due to toxicity, or up to 24 months (whichever comes first). For subjects with NSQ histology, pemetrexed maintenance was allowed until disease progression or unacceptable toxicity after 4 cycles of chemotherapy.

Arm type

Experimental

Investigational medicinal product name

No Treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Route of administration not applicable

Dosage and administration details

No Treatment

Part 2 - Arm I: Chemotherapy

Arm description

Chemotherapy-naive participants with stage IV or recurrent NSCLC irrespective of PD-L1 expressing levels received histology-based platinum-doublet chemotherapy IV in 3-week cycles for a maximum of 4 cycles or until disease progression or unacceptable toxicity (whichever comes first). For participants with NSQ histology, pemetrexed maintenance was allowed until disease progression or unacceptable toxicity after 4 cycles of chemotherapy.

Arm type

Active comparator

Investigational medicinal product name

No Treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Route of administration not applicable

Dosage and administration details

No Treatment

Part 3 -Arm J: Nivolumab + Ipilimumab

Arm description

Participants in China with PD-L1 Non Small Cell Lung Cancer received nivolumab 3 mg/kg IV over 30 minutes Q2W + ipilimumab 1 mg/kg over 30minutes every 6 weeks (Q6W) given for up to 24 months in the absence of disease progression or unacceptable toxicity.

Arm type

Active comparator

Investigational medicinal product name

No Treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Route of administration not applicable

Dosage and administration details

No Treatment

Part 3 - Arm K: Chemotherapy

Arm description

Participants in China with PD-L1 Non Small Cell Lung Cancer received histology-based platinum-doublet chemotherapy IV in3-week cycles for a maximum of 4 cycles or until disease progression or unacceptable toxicity (whichever comes first). For participants with NSQ histology, pemetrexed maintenance was allowed until disease progression or unacceptable toxicity after 4 cycles of chemotherapy.

Arm type

Active comparator

Investigational medicinal product name

No Treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Route of administration not applicable

Dosage and administration details

No Treatment

Number of subjects in period 1	Part 1-Arm B: Nivo + Ipi	Part 1-Arm A: Nivolumab	Part 1-Arm C: Chemotherapy	Part 1-Arm D: Nivo + Ipi	Part 1-Arm G: Nivo + Chemo	Part 1-Arm F: Chemotherapy	Part 2 - Arm H: Nivolumab + Chemotherapy	Part 2 - Arm I: Chemotherapy	Part 3 -Arm J: Nivolumab + Ipilimumab	Part 3 - Arm K: Chemotherapy
Started	396	396	397	187	177	186	377	378	126	127
Completed	391	391	387	185	172	183	375	371	126	123
Not completed	5	5	10	2	5	3	2	7	0	4
Adverse event, serious fatal	-	-	-	-	-	-	1	-	-	-
Subject withdrew consent	-	-	3	-	-	1	-	1	-	3
Subject request to discontinue study treatment	-	1	-	-	-	-	-	-	-	1
Adverse events unrelated to study drug	-	1	2	1	-	-	1	5	-	-
Other reasons	4	1	4	1	4	2	-	-	-	-
Subject no longer meets study criteria	1	2	1	-	1	-	-	1	-	-

Period 2 title

Treatment Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 1-Arm B: Nivo + Ipi

Arm description

Participants with PD-L1 Non Small Cell Lung Cancer received nivolumab 3 mg/kg IV over 30 minutes Q2W + ipilimumab 1 mg/kg over 30minutes every 6 weeks (Q6W) given for up to 24 months in the absence of disease progression or unacceptable toxicity.

Arm type

Experimental

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Part 1-Arm A: Nivolumab

Arm description

Participants with PD-L1 Non Small Cell Lung Cancer received nivolumab 240 mg intravenously (IV) over 30 minutes every 2 weeks (Q2W) given for up to 24months in the absence of disease progression or unacceptable toxicity.

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Part 1-Arm C: Chemotherapy

Arm description

Participants with PD-L1 Non Small Cell Lung Cancer received histology-based platinum-doublet chemotherapy IV in3-week cycles for a maximum of 4 cycles or until disease progression or unacceptable toxicity (whichever comes first). For participants with NSQ histology, pemetrexed maintenance was allowed until disease progression or unacceptable toxicity after 4 cycles of chemotherapy.

Arm type

Active comparator

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as SOC

Investigational medicinal product name

Pemetrexed

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Part 1-Arm D: Nivo + Ipi

Arm description

Arm type

Experimental

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Part 1-Arm G: Nivo + Chemo

Arm description

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Investigational medicinal product name

Pemetrexed

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as SOC

Part 1-Arm F: Chemotherapy

Arm description

Arm type

Active comparator

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as SOC

Investigational medicinal product name

Pemetrexed

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Part 2 - Arm H: Nivolumab + Chemotherapy

Arm description

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Investigational medicinal product name

Pemetrexed

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Part 2 - Arm I: Chemotherapy

Arm description

Arm type

Active comparator

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as SOC

Investigational medicinal product name

Pemetrexed

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Part 3 -Arm J: Nivolumab + Ipilimumab

Arm description

Arm type

Experimental

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Part 3 - Arm K: Chemotherapy

Arm description

Arm type

Active comparator

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as SOC

Investigational medicinal product name

Pemetrexed

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion.

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as infusion

Number of subjects in period 2	Part 1-Arm B: Nivo + Ipi	Part 1-Arm A: Nivolumab	Part 1-Arm C: Chemotherapy	Part 1-Arm D: Nivo + Ipi	Part 1-Arm G: Nivo + Chemo	Part 1-Arm F: Chemotherapy	Part 2 - Arm H: Nivolumab + Chemotherapy	Part 2 - Arm I: Chemotherapy	Part 3 -Arm J: Nivolumab + Ipilimumab	Part 3 - Arm K: Chemotherapy
Started	391	391	387	185	172	183	375	371	126	123
Completed	45	37	94	14	20	32	40	83	0	37
Not completed	346	354	293	171	152	151	335	288	126	86
Participant request to discontinue treatment	5	3	15	5	3	6	13	15	4	18
Adverse event, serious fatal	4	7	-	-	1	2	6	5	9	-
Disease progression	212	240	202	93	113	96	208	195	59	46
Maximum Clinical Benefit	3	3	1	1	3	-	3	2	2	2
Participant withdrew Consent	5	5	3	3	1	3	3	3	2	3
Other reasons	5	6	12	7	5	1	8	8	21	1
Study Drug Toxicity	79	51	31	39	12	25	52	30	20	9
Participant meet no longer study criteria	1	1	-	-	1	1	-	1	-	-
Not reported	8	6	4	4	2	1	14	8	5	2
Poor/Non Compliance	1	-	2	-	-	1	1	-	-	1
Pregnancy	-	-	-	-	-	-	-	-	-	1
Unknown	-	-	-	-	-	-	-	-	-	1
Adverse event unrelated to study drug	23	29	22	18	11	15	25	19	4	2
Lost to follow-up	-	-	1	1	-	-	2	2	-	-
Administrative reason by sponsor	-	3	-	-	-	-	-	-	-	-

Baseline characteristics

Top of page

Reporting group title

Part 1-Arm B: Nivo + Ipi

Reporting group description

Reporting group title

Part 1-Arm A: Nivolumab

Reporting group description

Reporting group title

Part 1-Arm C: Chemotherapy

Reporting group description

Reporting group title

Part 1-Arm D: Nivo + Ipi

Reporting group description

Reporting group title

Part 1-Arm G: Nivo + Chemo

Reporting group description

Reporting group title

Part 1-Arm F: Chemotherapy

Reporting group description

Reporting group title

Part 2 - Arm H: Nivolumab + Chemotherapy

Reporting group description

Reporting group title

Part 2 - Arm I: Chemotherapy

Reporting group description

Reporting group title

Part 3 -Arm J: Nivolumab + Ipilimumab

Reporting group description

Reporting group title

Part 3 - Arm K: Chemotherapy

Reporting group description

Reporting group values	Part 1-Arm B: Nivo + Ipi	Part 1-Arm A: Nivolumab	Part 1-Arm C: Chemotherapy	Part 1-Arm D: Nivo + Ipi	Part 1-Arm G: Nivo + Chemo	Part 1-Arm F: Chemotherapy	Part 2 - Arm H: Nivolumab + Chemotherapy	Part 2 - Arm I: Chemotherapy	Part 3 -Arm J: Nivolumab + Ipilimumab	Part 3 - Arm K: Chemotherapy	Total
Number of subjects	396	396	397	187	177	186	377	378	126	127	2747
Age Categorical
Units: participants
< 65	199	210	207	107	91	98	214	196	82	84	1488
=>65	197	186	190	80	86	88	163	182	44	43	1259
Age continuous
Units: years
arithmetic mean (standard deviation)	62.9 ( 9.70 )	63.5 ( 9.71 )	63.4 ( 9.22 )	63.1 ( 9.51 )	63.1 ( 9.58 )	63.3 ( 8.73 )	62.4 ( 9.84 )	62.5 ( 9.53 )	61.3 ( 7.6 )	61.2 ( 8.7 )	-
Sex: Female, Male
Units: participants
Female	141	124	137	49	47	61	113	115	18	20	825
Male	255	272	260	138	130	125	264	263	108	107	1922
Race/Ethnicity, Customized
Units: Subjects
White	299	317	305	143	136	133	272	266	0	0	1871
Black	4	6	5	0	2	2	1	3	0	0	23
Asian	84	67	82	41	38	45	93	94	126	127	797
Other	5	6	3	1	1	5	8	12	0	0	41
American Indian or Alaska Native	4	0	2	2	0	1	3	1	0	0	13
Native Hawaiian or other pacific islander	0	0	0	0	0	0	0	1	0	0	1
Not Reported	0	0	0	0	0	0	0	1	0	0	1

End points

Top of page

Reporting group title

Part 1-Arm B: Nivo + Ipi

Reporting group description

Reporting group title

Part 1-Arm A: Nivolumab

Reporting group description

Reporting group title

Part 1-Arm C: Chemotherapy

Reporting group description

Reporting group title

Part 1-Arm D: Nivo + Ipi

Reporting group description

Reporting group title

Part 1-Arm G: Nivo + Chemo

Reporting group description

Reporting group title

Part 1-Arm F: Chemotherapy

Reporting group description

Reporting group title

Part 2 - Arm H: Nivolumab + Chemotherapy

Reporting group description

Reporting group title

Part 2 - Arm I: Chemotherapy

Reporting group description

Reporting group title

Part 3 -Arm J: Nivolumab + Ipilimumab

Reporting group description

Reporting group title

Part 3 - Arm K: Chemotherapy

Reporting group description

Reporting group title

Part 1-Arm B: Nivo + Ipi

Reporting group description

Reporting group title

Part 1-Arm A: Nivolumab

Reporting group description

Reporting group title

Part 1-Arm C: Chemotherapy

Reporting group description

Reporting group title

Part 1-Arm D: Nivo + Ipi

Reporting group description

Reporting group title

Part 1-Arm G: Nivo + Chemo

Reporting group description

Reporting group title

Part 1-Arm F: Chemotherapy

Reporting group description

Reporting group title

Part 2 - Arm H: Nivolumab + Chemotherapy

Reporting group description

Reporting group title

Part 2 - Arm I: Chemotherapy

Reporting group description

Reporting group title

Part 3 -Arm J: Nivolumab + Ipilimumab

Reporting group description

Reporting group title

Part 3 - Arm K: Chemotherapy

Reporting group description

Primary: Progression-Free Survival per BICR

Top of page

End point title

Progression-Free Survival per BICR

End point description

Progression-Free Survival then (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first based on Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

End point type

Primary

End point timeframe

From randomization untill disease progression or death, whichever occurs first (up to approximately 481 weeks)

End point values	Part 1-Arm B: Nivo + Ipi	Part 1-Arm A: Nivolumab	Part 1-Arm C: Chemotherapy	Part 1-Arm D: Nivo + Ipi	Part 1-Arm G: Nivo + Chemo	Part 1-Arm F: Chemotherapy	Part 2 - Arm H: Nivolumab + Chemotherapy	Part 2 - Arm I: Chemotherapy	Part 3 -Arm J: Nivolumab + Ipilimumab	Part 3 - Arm K: Chemotherapy
Number of subjects analysed	396	396	397	187	177	186	377	378	126	127
Units: months
median (confidence interval 95%)	5.06 (4.07 to 6.31)	4.17 (3.22 to 5.32)	5.55 (4.63 to 5.82)	4.90 (3.15 to 6.28)	5.55 (4.63 to 6.90)	4.70 (4.21 to 5.59)	8.34 (7.10 to 9.59)	5.52 (4.47 to 5.85)	5.78 (4.14 to 8.34)	5.49 (4.37 to 6.77)

Statistical Analysis 2

Comparison groups

Part 1-Arm A: Nivolumab v Part 1-Arm C: Chemotherapy

Number of subjects included in analysis

793

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.12

Statistical Analysis 1

Comparison groups

Part 1-Arm B: Nivo + Ipi v Part 1-Arm C: Chemotherapy

Number of subjects included in analysis

793

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

0.93

Statistical Analysis 5

Comparison groups

Part 1-Arm F: Chemotherapy v Part 1-Arm G: Nivo + Chemo

Number of subjects included in analysis

363

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

0.93

Statistical Analysis 7

Comparison groups

Part 2 - Arm H: Nivolumab + Chemotherapy v Part 2 - Arm I: Chemotherapy

Number of subjects included in analysis

755

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

0.72

Statistical Analysis 7

Comparison groups

Part 3 -Arm J: Nivolumab + Ipilimumab v Part 3 - Arm K: Chemotherapy

Number of subjects included in analysis

253

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

0.89

Statistical Analysis 3

Comparison groups

Part 1-Arm B: Nivo + Ipi v Part 1-Arm A: Nivolumab

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

0.99

Statistical Analysis 4

Comparison groups

Part 1-Arm D: Nivo + Ipi v Part 1-Arm F: Chemotherapy

Number of subjects included in analysis

373

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Cox proportional hazard

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

0.97

Primary: Overall Survival

Top of page

End point title

Overall Survival

End point description

OS for all randomized participants is the time between randomization date and the date of death from any cause.

End point type

Primary

End point timeframe

From randomization untill death or last follow up whichever occurs first (up to approximately 481 weeks)

End point values	Part 1-Arm B: Nivo + Ipi	Part 1-Arm A: Nivolumab	Part 1-Arm C: Chemotherapy	Part 1-Arm D: Nivo + Ipi	Part 1-Arm G: Nivo + Chemo	Part 1-Arm F: Chemotherapy	Part 2 - Arm H: Nivolumab + Chemotherapy	Part 2 - Arm I: Chemotherapy	Part 3 -Arm J: Nivolumab + Ipilimumab	Part 3 - Arm K: Chemotherapy
Number of subjects analysed	396	396	397	187	177	186	377	378	126	127
Units: months
median (confidence interval 95%)	17.12 (14.95 to 20.17)	15.70 (13.27 to 18.14)	14.88 (12.71 to 16.72)	17.45 (13.21 to 22.05)	15.21 (12.29 to 19.78)	12.19 (9.17 to 14.32)	18.27 (15.84 to 21.65)	14.72 (12.42 to 16.79)	20.99 (16.95 to 25.17)	15.11 (13.17 to 18.89)

Statistical Analysis 1

Comparison groups

Part 1-Arm B: Nivo + Ipi v Part 1-Arm C: Chemotherapy

Number of subjects included in analysis

793

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

0.91

Statistical Analysis 2

Comparison groups

Part 1-Arm A: Nivolumab v Part 1-Arm C: Chemotherapy

Number of subjects included in analysis

793

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.05

Statistical Analysis 3

Comparison groups

Part 1-Arm B: Nivo + Ipi v Part 1-Arm A: Nivolumab

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.01

Statistical Analysis 7

Comparison groups

Part 3 -Arm J: Nivolumab + Ipilimumab v Part 3 - Arm K: Chemotherapy

Number of subjects included in analysis

253

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

1.14

Statistical Analysis 5

Comparison groups

Part 1-Arm G: Nivo + Chemo v Part 1-Arm F: Chemotherapy

Number of subjects included in analysis

363

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

0.96

Statistical Analysis 6

Comparison groups

Part 2 - Arm H: Nivolumab + Chemotherapy v Part 2 - Arm I: Chemotherapy

Number of subjects included in analysis

755

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.87

Statistical Analysis 4

Comparison groups

Part 1-Arm D: Nivo + Ipi v Part 1-Arm F: Chemotherapy

Number of subjects included in analysis

373

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

0.79

Secondary: Objective Response Rate (ORR) per BICR

Top of page

End point title

Objective Response Rate (ORR) per BICR

End point description

Objective response rate (ORR) is defined as the number of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

End point type

Secondary

End point timeframe

From randomization untill disease progression or death, whichever occurs first (up to approximately 481 weeks)

End point values	Part 1-Arm B: Nivo + Ipi	Part 1-Arm A: Nivolumab	Part 1-Arm C: Chemotherapy	Part 1-Arm D: Nivo + Ipi	Part 1-Arm G: Nivo + Chemo	Part 1-Arm F: Chemotherapy	Part 2 - Arm H: Nivolumab + Chemotherapy	Part 2 - Arm I: Chemotherapy	Part 3 -Arm J: Nivolumab + Ipilimumab	Part 3 - Arm K: Chemotherapy
Number of subjects analysed	396	396	397	187	177	186	377	378	126	127
Units: percentage of participants
number (confidence interval 95%)	36.4 (31.6 to 41.3)	27.5 (23.2 to 32.2)	29.7 (25.3 to 34.5)	26.2 (20.1 to 33.1)	37.9 (30.7 to 45.4)	23.1 (17.3 to 29.8)	52.3 (47.1 to 57.4)	29.9 (25.3 to 34.8)	38.1 (29.6 to 47.2)	30.7 (22.8 to 39.5)

No statistical analyses for this end point

Secondary: Percentage of Participants with Symptom Deterioration at Week 12 assessed via Lung Cancer Symptom Scale

Top of page

End point title

Percentage of Participants with Symptom Deterioration at Week 12 assessed via Lung Cancer Symptom Scale

End point description

The Lung Cancer Symptom Scale (LCSS) is a disease measure of quality of life which evaluates six major lung cancer symptoms and their effect on overall distress and symptom severity, impact on day-to-day activities, and overall quality of life. This patient reported outcome (PRO) questionnaire assesses the following 6 symptoms items (appetite loss, fatigue, cough, dyspnea, hemoptysis, pain) and 3 summary global items (symptom distress, activity level, overall quality of life) for patients using visual analogue scales (VAS) (100 mm horizontal line) ranging from 0 (best rating) to 100 (worst rating). The LCSS average total score is sum of items 1 to 9 divided by the total number of items ((sum of items 1 to 9)/9) ranging from 0 to 100 where high score represent worst outcome. Disease-Related Symptom Deterioration by Week 12 defined as a 10 points or more increase from baseline in LCSS average score at any time (on or off-treatment) up to 95 days from randomization date.

End point type

Secondary

End point timeframe

Week 12

End point values	Part 1-Arm B: Nivo + Ipi	Part 1-Arm A: Nivolumab	Part 1-Arm C: Chemotherapy	Part 1-Arm D: Nivo + Ipi	Part 1-Arm G: Nivo + Chemo	Part 1-Arm F: Chemotherapy	Part 2 - Arm H: Nivolumab + Chemotherapy	Part 2 - Arm I: Chemotherapy	Part 3 -Arm J: Nivolumab + Ipilimumab	Part 3 - Arm K: Chemotherapy
Number of subjects analysed	396	396	397	187	177	186	377	378	126	127
Units: percentage of participants
number (confidence interval 95%)	31.3 (26.8 to 36.1)	35.4 (30.6 to 40.3)	25.7 (21.5 to 30.3)	33.2 (26.5 to 40.4)	28.8 (22.3 to 36.1)	37.6 (30.7 to 45.0)	30.0 (25.4 to 34.9)	24.3 (20.1 to 29.0)	23.0 (16.0 to 31.4)	26.0 (18.6 to 34.5)

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Serious and non-serious adverse events were collected from first dose (Day 1) and 30 days after last dose of study therapy (up to approximately 105 months) and all cause mortality was collected from Day 1 and up to 481 weeks.

Adverse event reporting additional description

All treated participants

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.0

Reporting group title

Part 1-Arm A: Nivolumab

Reporting group description

Reporting group title

Part 1-Arm B: Nivo + Ipi

Reporting group description

Reporting group title

Part 1-Arm D: Nivo + Ipi

Reporting group description

Reporting group title

Part 1-Arm C: Chemotherapy

Reporting group description

Reporting group title

Part 1-Arm G: Nivo + Chemo

Reporting group description

Reporting group title

Part 1-Arm F: Chemotherapy

Reporting group description

Reporting group title

Part 2 - Arm H: Nivolumab + Chemotherapy

Reporting group description

Reporting group title

Part 2 - Arm I: Chemotherapy

Reporting group description

Reporting group title

Part 3 -Arm J: Nivolumab + Ipilimumab

Reporting group description

Reporting group title

Part 3 - Arm K: Chemotherapy

Reporting group description

Serious adverse events	Part 1-Arm A: Nivolumab	Part 1-Arm B: Nivo + Ipi	Part 1-Arm D: Nivo + Ipi	Part 1-Arm C: Chemotherapy	Part 1-Arm G: Nivo + Chemo	Part 1-Arm F: Chemotherapy	Part 2 - Arm H: Nivolumab + Chemotherapy	Part 2 - Arm I: Chemotherapy	Part 3 -Arm J: Nivolumab + Ipilimumab	Part 3 - Arm K: Chemotherapy
Total subjects affected by serious adverse events
subjects affected / exposed	239 / 391 (61.13%)	275 / 391 (70.33%)	128 / 185 (69.19%)	213 / 387 (55.04%)	112 / 172 (65.12%)	91 / 183 (49.73%)	240 / 375 (64.00%)	180 / 371 (48.52%)	78 / 126 (61.90%)	60 / 123 (48.78%)
number of deaths (all causes)	333	316	159	339	157	174	314	335	95	94
number of deaths resulting from adverse events	114	115	44	97	52	50	112	86	29	15
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute leukaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Benign breast neoplasm
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bladder transitional cell carcinoma
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cancer pain
subjects affected / exposed	3 / 391 (0.77%)	5 / 391 (1.28%)	3 / 185 (1.62%)	3 / 387 (0.78%)	1 / 172 (0.58%)	1 / 183 (0.55%)	1 / 375 (0.27%)	5 / 371 (1.35%)	1 / 126 (0.79%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 4	0 / 6	0 / 3	0 / 3	0 / 1	0 / 1	0 / 1	0 / 5	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
Cholangiocarcinoma
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Colon cancer
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic myeloid leukaemia
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Extranodal marginal zone B-cell lymphoma (MALT type)
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemangioma
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric neoplasm
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Female reproductive neoplasm
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematological malignancy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic cancer
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary cancer
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infected neoplasm
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal adenocarcinoma
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal metastasis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Lung cancer metastatic
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung adenocarcinoma
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphangiosis carcinomatosa
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	2 / 185 (1.08%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to meninges
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Metastases to central nervous system
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to bone
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to adrenals
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant neoplasm progression
subjects affected / exposed	102 / 391 (26.09%)	98 / 391 (25.06%)	39 / 185 (21.08%)	87 / 387 (22.48%)	48 / 172 (27.91%)	41 / 183 (22.40%)	81 / 375 (21.60%)	78 / 371 (21.02%)	18 / 126 (14.29%)	9 / 123 (7.32%)
occurrences causally related to treatment / all	0 / 114	0 / 105	0 / 43	0 / 92	0 / 53	0 / 43	0 / 90	0 / 81	1 / 18	0 / 9
deaths causally related to treatment / all	0 / 81	0 / 80	0 / 29	0 / 73	0 / 39	0 / 37	0 / 70	0 / 66	1 / 15	0 / 9
Metastases to pleura
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paraneoplastic syndrome
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oncologic complication
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neoplasm progression
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neoplasm malignant
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Metastasis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tumour associated fever
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tumour compression
subjects affected / exposed	2 / 391 (0.51%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tumour haemorrhage
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tumour invasion
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tumour pseudoprogression
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tumour pain
subjects affected / exposed	2 / 391 (0.51%)	2 / 391 (0.51%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	1 / 371 (0.27%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 2	0 / 0	0 / 0	0 / 2	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
Tumour necrosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Arterial thrombosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aortic thrombosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arteritis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Extremity necrosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Embolism
subjects affected / exposed	3 / 391 (0.77%)	2 / 391 (0.51%)	0 / 185 (0.00%)	2 / 387 (0.52%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	2 / 391 (0.51%)	2 / 391 (0.51%)	2 / 185 (1.08%)	2 / 387 (0.52%)	0 / 172 (0.00%)	1 / 183 (0.55%)	4 / 375 (1.07%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	1 / 2	0 / 2	0 / 0	0 / 1	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Circulatory collapse
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Haematoma
subjects affected / exposed	2 / 391 (0.51%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypovolaemic shock
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Hypotension
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infarction
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral embolism
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Shock
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subclavian vein thrombosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Superficial vein thrombosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Superior vena cava occlusion
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Superior vena cava syndrome
subjects affected / exposed	2 / 391 (0.51%)	2 / 391 (0.51%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vasculitis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vena cava thrombosis
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Venous thrombosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	2 / 371 (0.54%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Venous thrombosis limb
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Pregnancy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	4 / 391 (1.02%)	3 / 391 (0.77%)	5 / 185 (2.70%)	5 / 387 (1.29%)	2 / 172 (1.16%)	0 / 183 (0.00%)	2 / 375 (0.53%)	3 / 371 (0.81%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 4	1 / 3	1 / 5	1 / 5	0 / 2	0 / 0	2 / 2	2 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Adverse drug reaction
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	2 / 391 (0.51%)	1 / 391 (0.26%)	1 / 185 (0.54%)	1 / 387 (0.26%)	0 / 172 (0.00%)	3 / 183 (1.64%)	1 / 375 (0.27%)	1 / 371 (0.27%)	1 / 126 (0.79%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 1	0 / 0	0 / 3	0 / 1	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 1	0 / 0	0 / 3	0 / 1	0 / 1	0 / 1	0 / 1
Complication associated with device
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chills
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug withdrawal syndrome
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chest discomfort
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	3 / 391 (0.77%)	3 / 391 (0.77%)	1 / 185 (0.54%)	1 / 387 (0.26%)	4 / 172 (2.33%)	1 / 183 (0.55%)	1 / 375 (0.27%)	2 / 371 (0.54%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 3	1 / 3	1 / 1	0 / 1	2 / 5	1 / 1	1 / 1	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Face oedema
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	4 / 391 (1.02%)	0 / 391 (0.00%)	1 / 185 (0.54%)	3 / 387 (0.78%)	1 / 172 (0.58%)	4 / 183 (2.19%)	1 / 375 (0.27%)	3 / 371 (0.81%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1	1 / 3	0 / 1	0 / 4	1 / 1	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperthermia
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Generalised oedema
subjects affected / exposed	2 / 391 (0.51%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mucosal inflammation
subjects affected / exposed	3 / 391 (0.77%)	0 / 391 (0.00%)	1 / 185 (0.54%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malaise
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza like illness
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inflammation
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypothermia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	5 / 391 (1.28%)	5 / 391 (1.28%)	3 / 185 (1.62%)	5 / 387 (1.29%)	3 / 172 (1.74%)	3 / 183 (1.64%)	6 / 375 (1.60%)	5 / 371 (1.35%)	6 / 126 (4.76%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 5	2 / 5	0 / 3	2 / 5	0 / 4	0 / 3	1 / 6	2 / 7	4 / 6	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Performance status decreased
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	1 / 183 (0.55%)	3 / 375 (0.80%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sudden death
subjects affected / exposed	5 / 391 (1.28%)	3 / 391 (0.77%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	1 / 183 (0.55%)	6 / 375 (1.60%)	2 / 371 (0.54%)	4 / 126 (3.17%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 5	0 / 3	0 / 0	0 / 0	0 / 1	0 / 1	0 / 6	0 / 2	1 / 4	0 / 1
deaths causally related to treatment / all	0 / 5	0 / 3	0 / 0	0 / 0	0 / 1	0 / 1	0 / 6	0 / 2	1 / 4	0 / 1
Multiple organ dysfunction syndrome
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Swelling
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anaphylactic shock
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypersensitivity
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug hypersensitivity
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Contrast media reaction
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Contrast media allergy
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infusion related hypersensitivity reaction
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intermenstrual bleeding
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic pain
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Vaginal prolapse
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	3 / 387 (0.78%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Apnoea
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Aspiration
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	2 / 371 (0.54%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchial haemorrhage
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchial obstruction
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	3 / 391 (0.77%)	2 / 391 (0.51%)	2 / 185 (1.08%)	1 / 387 (0.26%)	5 / 172 (2.91%)	1 / 183 (0.55%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 4	0 / 1	0 / 5	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Cough
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	9 / 391 (2.30%)	8 / 391 (2.05%)	2 / 185 (1.08%)	8 / 387 (2.07%)	1 / 172 (0.58%)	2 / 183 (1.09%)	4 / 375 (1.07%)	5 / 371 (1.35%)	1 / 126 (0.79%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 9	0 / 9	0 / 3	0 / 8	0 / 2	0 / 2	1 / 5	0 / 5	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
Emphysema
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	2 / 391 (0.51%)	2 / 391 (0.51%)	3 / 185 (1.62%)	7 / 387 (1.81%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	1 / 371 (0.27%)	4 / 126 (3.17%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 3	0 / 8	0 / 0	0 / 0	0 / 2	0 / 1	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercapnia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	2 / 391 (0.51%)	2 / 391 (0.51%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	2 / 391 (0.51%)	4 / 391 (1.02%)	2 / 185 (1.08%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	3 / 126 (2.38%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	2 / 2	4 / 4	2 / 2	1 / 1	1 / 1	0 / 0	1 / 1	0 / 0	4 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated lung disease
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung disorder
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung infiltration
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Lung opacity
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant pleural effusion
subjects affected / exposed	4 / 391 (1.02%)	9 / 391 (2.30%)	3 / 185 (1.62%)	1 / 387 (0.26%)	1 / 172 (0.58%)	4 / 183 (2.19%)	2 / 375 (0.53%)	2 / 371 (0.54%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 10	0 / 3	0 / 1	0 / 1	0 / 4	0 / 2	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mediastinal disorder
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Obstructive airways disorder
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Oesophagobronchial fistula
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Organising pneumonia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleurisy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	4 / 391 (1.02%)	5 / 391 (1.28%)	1 / 185 (0.54%)	1 / 387 (0.26%)	3 / 172 (1.74%)	1 / 183 (0.55%)	7 / 375 (1.87%)	5 / 371 (1.35%)	3 / 126 (2.38%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 5	2 / 6	0 / 1	0 / 1	1 / 3	0 / 1	0 / 7	0 / 6	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	11 / 391 (2.81%)	20 / 391 (5.12%)	7 / 185 (3.78%)	4 / 387 (1.03%)	5 / 172 (2.91%)	1 / 183 (0.55%)	14 / 375 (3.73%)	1 / 371 (0.27%)	11 / 126 (8.73%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	11 / 11	23 / 25	8 / 8	2 / 4	6 / 6	1 / 1	11 / 14	1 / 1	11 / 12	0 / 0
deaths causally related to treatment / all	2 / 2	2 / 2	1 / 1	1 / 1	0 / 0	0 / 0	2 / 3	0 / 0	2 / 2	0 / 0
Productive cough
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 391 (0.26%)	3 / 391 (0.77%)	1 / 185 (0.54%)	2 / 387 (0.52%)	0 / 172 (0.00%)	1 / 183 (0.55%)	5 / 375 (1.33%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 1	0 / 2	0 / 0	1 / 1	1 / 6	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	7 / 391 (1.79%)	13 / 391 (3.32%)	4 / 185 (2.16%)	5 / 387 (1.29%)	6 / 172 (3.49%)	2 / 183 (1.09%)	9 / 375 (2.40%)	5 / 371 (1.35%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 7	0 / 13	0 / 4	1 / 6	1 / 6	0 / 2	1 / 9	1 / 5	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 3	0 / 3	0 / 0	0 / 0	1 / 1	0 / 0	0 / 4	0 / 0	0 / 0	0 / 1
Pulmonary haemorrhage
subjects affected / exposed	2 / 391 (0.51%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Pulmonary hilum mass
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary venous thrombosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory alkalosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	4 / 391 (1.02%)	2 / 391 (0.51%)	5 / 185 (2.70%)	5 / 387 (1.29%)	3 / 172 (1.74%)	3 / 183 (1.64%)	6 / 375 (1.60%)	3 / 371 (0.81%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 5	0 / 2	0 / 6	1 / 7	2 / 4	0 / 3	1 / 6	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 3	0 / 1	0 / 2	0 / 1	1 / 1	0 / 3	1 / 5	0 / 3	0 / 0	0 / 1
Wheezing
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bipolar disorder
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Delirium
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Confusional state
subjects affected / exposed	0 / 391 (0.00%)	3 / 391 (0.77%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Completed suicide
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Disorientation
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	2 / 391 (0.51%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	2 / 172 (1.16%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1	1 / 2	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device dislocation
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device physical property issue
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Acute hepatic failure
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune hepatitis
subjects affected / exposed	0 / 391 (0.00%)	3 / 391 (0.77%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 3	0 / 0	0 / 1	0 / 0	0 / 0	2 / 2	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bile duct stone
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholangitis acute
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Biliary obstruction
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	2 / 391 (0.51%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	1 / 183 (0.55%)	2 / 375 (0.53%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholestasis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug-induced liver injury
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	3 / 123 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	3 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis
subjects affected / exposed	4 / 391 (1.02%)	3 / 391 (0.77%)	6 / 185 (3.24%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	3 / 4	2 / 3	6 / 6	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic function abnormal
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	2 / 185 (1.08%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	2 / 2	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatorenal failure
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Hepatotoxicity
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hydrocholecystis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperbilirubinaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertransaminasaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated hepatic disorder
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated hepatitis
subjects affected / exposed	0 / 391 (0.00%)	3 / 391 (0.77%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	7 / 126 (5.56%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	3 / 3	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	7 / 7	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
Jaundice cholestatic
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Liver disorder
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Liver injury
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Amylase increased
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Alanine aminotransferase increased
subjects affected / exposed	3 / 391 (0.77%)	2 / 391 (0.51%)	1 / 185 (0.54%)	0 / 387 (0.00%)	2 / 172 (1.16%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	3 / 3	2 / 2	0 / 1	0 / 0	2 / 2	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	2 / 185 (1.08%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood glucose increased
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	3 / 375 (0.80%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	4 / 5	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood calcium decreased
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General physical condition abnormal
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eosinophil count increased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood potassium decreased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphocyte count decreased
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Liver function test increased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Liver function test abnormal
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lipase increased
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	2 / 185 (1.08%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	2 / 375 (0.53%)	3 / 371 (0.81%)	0 / 126 (0.00%)	4 / 123 (3.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	2 / 2	3 / 3	0 / 0	4 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	3 / 387 (0.78%)	0 / 172 (0.00%)	1 / 183 (0.55%)	6 / 375 (1.60%)	2 / 371 (0.54%)	3 / 126 (2.38%)	8 / 123 (6.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	3 / 3	0 / 0	0 / 1	6 / 6	3 / 3	2 / 3	8 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Pancreatic enzymes increased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Weight decreased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Troponin increased
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
White blood cell count decreased
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	3 / 375 (0.80%)	0 / 371 (0.00%)	0 / 126 (0.00%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	3 / 3	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Acetabulum fracture
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Accidental overdose
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Contusion
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Forearm fracture
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femoral nerve injury
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	3 / 391 (0.77%)	1 / 391 (0.26%)	1 / 185 (0.54%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 1	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	2 / 183 (1.09%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fracture displacement
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Multiple fractures
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Limb injury
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ligament sprain
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle strain
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	2 / 387 (0.52%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 4	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural complication
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radiation pneumonitis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radiation oesophagitis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound dehiscence
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	1 / 391 (0.26%)	2 / 391 (0.51%)	2 / 185 (1.08%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Acute left ventricular failure
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute coronary syndrome
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arteriosclerosis coronary artery
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	4 / 391 (1.02%)	4 / 391 (1.02%)	4 / 185 (2.16%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	3 / 375 (0.80%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 4	1 / 4	1 / 4	0 / 0	0 / 1	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	1 / 183 (0.55%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	4 / 391 (1.02%)	2 / 391 (0.51%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	2 / 391 (0.51%)	3 / 391 (0.77%)	3 / 185 (1.62%)	1 / 387 (0.26%)	1 / 172 (0.58%)	2 / 183 (1.09%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 3	1 / 1	0 / 2	0 / 4	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	1 / 183 (0.55%)	0 / 375 (0.00%)	1 / 371 (0.27%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0	0 / 1	0 / 1	0 / 0
Cardiac tamponade
subjects affected / exposed	3 / 391 (0.77%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac fibrillation
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	1 / 185 (0.54%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	2 / 2	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure acute
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiogenic shock
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiopulmonary failure
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive cardiomyopathy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated myocarditis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	2 / 126 (1.59%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	3 / 185 (1.62%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	3 / 375 (0.80%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0	1 / 1	0 / 0	3 / 3	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Palpitations
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial effusion malignant
subjects affected / exposed	4 / 391 (1.02%)	0 / 391 (0.00%)	2 / 185 (1.08%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	5 / 391 (1.28%)	2 / 391 (0.51%)	1 / 185 (0.54%)	2 / 387 (0.52%)	1 / 172 (0.58%)	1 / 183 (0.55%)	0 / 375 (0.00%)	3 / 371 (0.81%)	2 / 126 (1.59%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	2 / 5	0 / 2	0 / 1	0 / 2	1 / 1	0 / 1	0 / 0	1 / 3	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleuropericarditis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stress cardiomyopathy
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Right ventricular failure
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Supraventricular extrasystoles
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Supraventricular tachyarrhythmia
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Torsade de pointes
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Brain oedema
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atonic seizures
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebellar infarction
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	1 / 185 (0.54%)	4 / 387 (1.03%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	1 / 4	1 / 1	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral haemorrhage
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral ischaemia
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral microangiopathy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	5 / 391 (1.28%)	4 / 391 (1.02%)	3 / 185 (1.62%)	3 / 387 (0.78%)	2 / 172 (1.16%)	1 / 183 (0.55%)	1 / 375 (0.27%)	3 / 371 (0.81%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 5	0 / 3	0 / 3	0 / 2	0 / 1	0 / 1	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 2	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Dizziness
subjects affected / exposed	2 / 391 (0.51%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	1 / 183 (0.55%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular disorder
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysarthria
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Encephalitis autoimmune
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Embolic cerebral infarction
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Facial paralysis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Haemorrhagic stroke
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhagic transformation stroke
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 391 (0.26%)	3 / 391 (0.77%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hemiparesis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoaesthesia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhagic cerebral infarction
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	2 / 185 (1.08%)	3 / 387 (0.78%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 3	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lethargy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar radiculopathy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myasthenia gravis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myasthenic syndrome
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nerve compression
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neuralgia
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neuropathy peripheral
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paralysis recurrent laryngeal nerve
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paraplegia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Polyneuropathy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Partial seizures
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sensory loss
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	1 / 185 (0.54%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 4	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Quadriparesis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Somnolence
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal cord compression
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	2 / 387 (0.52%)	1 / 172 (0.58%)	1 / 183 (0.55%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	1 / 183 (0.55%)	0 / 375 (0.00%)	2 / 371 (0.54%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vasogenic cerebral oedema
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vocal cord paralysis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vertebrobasilar artery dissection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	4 / 391 (1.02%)	4 / 391 (1.02%)	4 / 185 (2.16%)	9 / 387 (2.33%)	10 / 172 (5.81%)	8 / 183 (4.37%)	14 / 375 (3.73%)	10 / 371 (2.70%)	1 / 126 (0.79%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	1 / 4	2 / 4	1 / 4	9 / 11	7 / 11	11 / 13	13 / 17	8 / 13	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune haemolytic anaemia
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	3 / 391 (0.77%)	0 / 391 (0.00%)	2 / 185 (1.08%)	9 / 387 (2.33%)	4 / 172 (2.33%)	7 / 183 (3.83%)	16 / 375 (4.27%)	6 / 371 (1.62%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 2	7 / 10	1 / 4	5 / 7	17 / 18	8 / 8	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
Eosinophilia
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile bone marrow aplasia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	2 / 371 (0.54%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bone marrow failure
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Iron deficiency anaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Heparin-induced thrombocytopenia
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematotoxicity
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myelosuppression
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	7 / 123 (5.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0	7 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	2 / 387 (0.52%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	1 / 1	0 / 0	0 / 1	1 / 1	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	3 / 391 (0.77%)	0 / 391 (0.00%)	0 / 185 (0.00%)	2 / 387 (0.52%)	4 / 172 (2.33%)	1 / 183 (0.55%)	5 / 375 (1.33%)	4 / 371 (1.08%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 0	2 / 2	4 / 5	1 / 1	6 / 6	5 / 5	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
Splenic haematoma
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Splenic haemorrhage
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	5 / 387 (1.29%)	4 / 172 (2.33%)	1 / 183 (0.55%)	2 / 375 (0.53%)	2 / 371 (0.54%)	0 / 126 (0.00%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	5 / 5	4 / 4	1 / 1	2 / 2	2 / 2	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Splenic thrombosis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Sudden hearing loss
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vertigo
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diplopia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal hernia
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal distension
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	2 / 391 (0.51%)	0 / 391 (0.00%)	0 / 185 (0.00%)	2 / 387 (0.52%)	1 / 172 (0.58%)	0 / 183 (0.00%)	4 / 375 (1.07%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	2 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ascites
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	4 / 391 (1.02%)	9 / 391 (2.30%)	3 / 185 (1.62%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	4 / 375 (1.07%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	5 / 5	9 / 10	3 / 3	0 / 0	1 / 1	0 / 0	5 / 5	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune colitis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis ischaemic
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis microscopic
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	2 / 391 (0.51%)	3 / 391 (0.77%)	2 / 185 (1.08%)	2 / 387 (0.52%)	0 / 172 (0.00%)	3 / 183 (1.64%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 2	1 / 2	0 / 0	1 / 3	0 / 0	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	3 / 391 (0.77%)	6 / 391 (1.53%)	9 / 185 (4.86%)	4 / 387 (1.03%)	1 / 172 (0.58%)	3 / 183 (1.64%)	6 / 375 (1.60%)	2 / 371 (0.54%)	4 / 126 (3.17%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	2 / 3	6 / 6	8 / 10	3 / 4	0 / 1	2 / 3	5 / 6	2 / 2	3 / 5	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	1 / 391 (0.26%)	3 / 391 (0.77%)	1 / 185 (0.54%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 3	0 / 1	0 / 1	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	0 / 391 (0.00%)	3 / 391 (0.77%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	4 / 4	0 / 0	0 / 0	0 / 0	2 / 3	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erosive oesophagitis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 391 (0.00%)	3 / 391 (0.77%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	4 / 4	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorder
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	2 / 387 (0.52%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gingival hypertrophy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoidal haemorrhage
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated enterocolitis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
Ileus
subjects affected / exposed	2 / 391 (0.51%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated gastritis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal ischaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Immune-mediated pancreatitis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	3 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Melaena
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant ascites
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
Large intestinal ulcer
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Oesophageal stenosis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal ulcer
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal fistula
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Odynophagia
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	2 / 391 (0.51%)	1 / 391 (0.26%)	1 / 185 (0.54%)	7 / 387 (1.81%)	1 / 172 (0.58%)	4 / 183 (2.19%)	2 / 375 (0.53%)	4 / 371 (1.08%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	4 / 7	1 / 1	3 / 6	2 / 2	5 / 5	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal ulcer
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	2 / 391 (0.51%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	7 / 391 (1.79%)	1 / 391 (0.26%)	2 / 185 (1.08%)	7 / 387 (1.81%)	1 / 172 (0.58%)	2 / 183 (1.09%)	5 / 375 (1.33%)	4 / 371 (1.08%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 7	1 / 1	1 / 2	6 / 7	1 / 1	1 / 3	3 / 5	3 / 4	2 / 3	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subileus
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Diabetic foot
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune dermatitis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug eruption
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erythema multiforme
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Exfoliative rash
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erythema
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eczema
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutrophilic dermatosis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rash
subjects affected / exposed	2 / 391 (0.51%)	2 / 391 (0.51%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	2 / 126 (1.59%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	2 / 2	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pruritus
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rash maculo-papular
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	2 / 185 (1.08%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	2 / 2	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rash vesicular
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rash pruritic
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin ulcer
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stevens-Johnson syndrome
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Toxic skin eruption
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	4 / 391 (1.02%)	2 / 391 (0.51%)	3 / 185 (1.62%)	4 / 387 (1.03%)	2 / 172 (1.16%)	0 / 183 (0.00%)	2 / 375 (0.53%)	2 / 371 (0.54%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	1 / 5	2 / 2	1 / 4	3 / 4	3 / 4	0 / 0	2 / 2	2 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune nephritis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Azotaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nephrogenic diabetes insipidus
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nephropathy toxic
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 391 (0.26%)	3 / 391 (0.77%)	0 / 185 (0.00%)	2 / 387 (0.52%)	1 / 172 (0.58%)	0 / 183 (0.00%)	3 / 375 (0.80%)	3 / 371 (0.81%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 3	0 / 0	0 / 2	0 / 1	0 / 0	2 / 3	2 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Tubulointerstitial nephritis
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal vascular thrombosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ureterolithiasis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Hypercalcaemia of malignancy
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune thyroiditis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune hypothyroidism
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Adrenal insufficiency
subjects affected / exposed	1 / 391 (0.26%)	10 / 391 (2.56%)	6 / 185 (3.24%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	9 / 10	7 / 7	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperparathyroidism secondary
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperthyroidism
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypophysitis
subjects affected / exposed	0 / 391 (0.00%)	5 / 391 (1.28%)	2 / 185 (1.08%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	2 / 126 (1.59%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	6 / 6	2 / 2	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypothyroidism
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypopituitarism
subjects affected / exposed	1 / 391 (0.26%)	5 / 391 (1.28%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	5 / 5	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inappropriate antidiuretic hormone secretion
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Primary adrenal insufficiency
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Secondary adrenocortical insufficiency
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated hypophysitis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 1	0 / 0	0 / 0	1 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune arthritis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	2 / 391 (0.51%)	1 / 391 (0.26%)	3 / 185 (1.62%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 5	0 / 1	0 / 1	0 / 0	0 / 3	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bone pain
subjects affected / exposed	1 / 391 (0.26%)	2 / 391 (0.51%)	2 / 185 (1.08%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Flank pain
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertrophic osteoarthropathy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myalgia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myopathy
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myositis
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteonecrosis of jaw
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	1 / 375 (0.27%)	2 / 371 (0.54%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	1 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Polyarthritis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Polymyalgia rheumatica
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abscess limb
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Aspergillus infection
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	4 / 375 (1.07%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 4	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial diarrhoea
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopulmonary aspergillosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 391 (0.26%)	3 / 391 (0.77%)	1 / 185 (0.54%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	5 / 375 (1.33%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 3	0 / 1	0 / 1	0 / 1	0 / 0	0 / 5	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	2 / 183 (1.09%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Catheter site infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic foot infection
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dermo-hypodermitis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	4 / 172 (2.33%)	0 / 183 (0.00%)	3 / 375 (0.80%)	4 / 371 (1.08%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	1 / 5	0 / 0	0 / 4	1 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enteritis infectious
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Encephalitis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Empyema
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis intestinal perforated
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Enterocolitis infectious
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	2 / 185 (1.08%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile infection
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Groin infection
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infectious pleural effusion
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infective exacerbation of chronic obstructive airways disease
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injection site infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Klebsiella urinary tract infection
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine infection
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	1 / 185 (0.54%)	1 / 387 (0.26%)	3 / 172 (1.74%)	0 / 183 (0.00%)	2 / 375 (0.53%)	2 / 371 (0.54%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 1	0 / 1	1 / 4	0 / 0	0 / 3	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung abscess
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nasopharyngitis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenic infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenic sepsis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	2 / 185 (1.08%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	1 / 1	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis viral
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metapneumovirus infection
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myelitis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Parainfluenzae virus infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ophthalmic herpes zoster
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal candidiasis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	2 / 185 (1.08%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	29 / 391 (7.42%)	40 / 391 (10.23%)	18 / 185 (9.73%)	31 / 387 (8.01%)	15 / 172 (8.72%)	8 / 183 (4.37%)	34 / 375 (9.07%)	29 / 371 (7.82%)	11 / 126 (8.73%)	8 / 123 (6.50%)
occurrences causally related to treatment / all	2 / 32	1 / 43	0 / 22	2 / 33	3 / 19	0 / 8	8 / 46	5 / 34	1 / 14	1 / 8
deaths causally related to treatment / all	0 / 4	0 / 6	0 / 5	0 / 7	0 / 3	0 / 2	0 / 4	0 / 2	0 / 1	0 / 0
Pleural infection
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia adenoviral
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	2 / 391 (0.51%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	2 / 183 (1.09%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia influenzal
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia klebsiella
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia necrotising
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Pseudomembranous colitis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	3 / 391 (0.77%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal abscess
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	5 / 391 (1.28%)	4 / 391 (1.02%)	4 / 185 (2.16%)	3 / 387 (0.78%)	2 / 172 (1.16%)	1 / 183 (0.55%)	1 / 375 (0.27%)	3 / 371 (0.81%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 7	1 / 4	0 / 4	0 / 3	0 / 5	0 / 2	0 / 1	1 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection viral
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Salmonellosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	3 / 391 (0.77%)	3 / 391 (0.77%)	1 / 185 (0.54%)	3 / 387 (0.78%)	1 / 172 (0.58%)	4 / 183 (2.19%)	7 / 375 (1.87%)	2 / 371 (0.54%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 4	0 / 1	3 / 3	0 / 1	0 / 4	3 / 8	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 2	0 / 0	2 / 2	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	4 / 391 (1.02%)	2 / 391 (0.51%)	4 / 185 (2.16%)	1 / 387 (0.26%)	0 / 172 (0.00%)	2 / 183 (1.09%)	1 / 375 (0.27%)	1 / 371 (0.27%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 4	1 / 1	0 / 0	0 / 2	1 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 0	0 / 0	0 / 2	1 / 1	0 / 1	0 / 0	0 / 0
Skin infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Soft tissue infection
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Systemic candida
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombophlebitis septic
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tooth infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	5 / 387 (1.29%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 5	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral pericarditis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular device infection
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	2 / 371 (0.54%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	2 / 391 (0.51%)	4 / 391 (1.02%)	1 / 185 (0.54%)	4 / 387 (1.03%)	1 / 172 (0.58%)	0 / 183 (0.00%)	2 / 375 (0.53%)	3 / 371 (0.81%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 1	0 / 4	0 / 1	0 / 0	0 / 3	0 / 4	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Acidosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Adult failure to thrive
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Decreased appetite
subjects affected / exposed	2 / 391 (0.51%)	1 / 391 (0.26%)	1 / 185 (0.54%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	4 / 375 (1.07%)	3 / 371 (0.81%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 1	0 / 0	0 / 0	2 / 2	2 / 4	3 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	4 / 391 (1.02%)	2 / 391 (0.51%)	0 / 185 (0.00%)	1 / 387 (0.26%)	1 / 172 (0.58%)	1 / 183 (0.55%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 0	0 / 1	1 / 1	0 / 1	0 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic metabolic decompensation
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	1 / 183 (0.55%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Electrolyte imbalance
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	4 / 391 (1.02%)	3 / 391 (0.77%)	1 / 185 (0.54%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	2 / 371 (0.54%)	0 / 126 (0.00%)	2 / 123 (1.63%)
occurrences causally related to treatment / all	0 / 4	0 / 3	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 391 (0.00%)	2 / 391 (0.51%)	3 / 185 (1.62%)	1 / 387 (0.26%)	0 / 172 (0.00%)	0 / 183 (0.00%)	4 / 375 (1.07%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 3	0 / 1	0 / 0	0 / 0	0 / 4	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypermagnesaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperuricaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	1 / 126 (0.79%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypocalcaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	2 / 185 (1.08%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 1	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypomagnesaemia
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoproteinaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	3 / 391 (0.77%)	3 / 391 (0.77%)	1 / 185 (0.54%)	2 / 387 (0.52%)	1 / 172 (0.58%)	0 / 183 (0.00%)	6 / 375 (1.60%)	1 / 371 (0.27%)	3 / 126 (2.38%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 3	2 / 3	0 / 1	1 / 3	0 / 1	0 / 0	1 / 6	1 / 1	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Ketoacidosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Type 1 diabetes mellitus
subjects affected / exposed	1 / 391 (0.26%)	3 / 391 (0.77%)	1 / 185 (0.54%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	1 / 1	3 / 3	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	1 / 371 (0.27%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Part 1-Arm A: Nivolumab	Part 1-Arm B: Nivo + Ipi	Part 1-Arm D: Nivo + Ipi	Part 1-Arm C: Chemotherapy	Part 1-Arm G: Nivo + Chemo	Part 1-Arm F: Chemotherapy	Part 2 - Arm H: Nivolumab + Chemotherapy	Part 2 - Arm I: Chemotherapy	Part 3 -Arm J: Nivolumab + Ipilimumab	Part 3 - Arm K: Chemotherapy
Total subjects affected by non serious adverse events
subjects affected / exposed	356 / 391 (91.05%)	366 / 391 (93.61%)	172 / 185 (92.97%)	361 / 387 (93.28%)	167 / 172 (97.09%)	165 / 183 (90.16%)	357 / 375 (95.20%)	345 / 371 (92.99%)	124 / 126 (98.41%)	121 / 123 (98.37%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	18 / 391 (4.60%)	9 / 391 (2.30%)	5 / 185 (2.70%)	11 / 387 (2.84%)	9 / 172 (5.23%)	2 / 183 (1.09%)	12 / 375 (3.20%)	12 / 371 (3.23%)	3 / 126 (2.38%)	2 / 123 (1.63%)
occurrences all number	19	9	5	13	9	2	12	12	3	2
Vascular disorders
Hypertension
subjects affected / exposed	15 / 391 (3.84%)	21 / 391 (5.37%)	8 / 185 (4.32%)	13 / 387 (3.36%)	12 / 172 (6.98%)	8 / 183 (4.37%)	21 / 375 (5.60%)	8 / 371 (2.16%)	8 / 126 (6.35%)	3 / 123 (2.44%)
occurrences all number	18	24	15	14	15	11	28	11	8	4
Hypotension
subjects affected / exposed	13 / 391 (3.32%)	16 / 391 (4.09%)	6 / 185 (3.24%)	9 / 387 (2.33%)	10 / 172 (5.81%)	8 / 183 (4.37%)	9 / 375 (2.40%)	8 / 371 (2.16%)	5 / 126 (3.97%)	1 / 123 (0.81%)
occurrences all number	14	18	7	11	11	8	10	9	5	1
General disorders and administration site conditions
Chest discomfort
subjects affected / exposed	3 / 391 (0.77%)	4 / 391 (1.02%)	2 / 185 (1.08%)	3 / 387 (0.78%)	3 / 172 (1.74%)	0 / 183 (0.00%)	6 / 375 (1.60%)	7 / 371 (1.89%)	14 / 126 (11.11%)	7 / 123 (5.69%)
occurrences all number	3	4	2	3	4	0	6	8	16	9
Asthenia
subjects affected / exposed	78 / 391 (19.95%)	93 / 391 (23.79%)	40 / 185 (21.62%)	66 / 387 (17.05%)	35 / 172 (20.35%)	42 / 183 (22.95%)	70 / 375 (18.67%)	52 / 371 (14.02%)	17 / 126 (13.49%)	11 / 123 (8.94%)
occurrences all number	104	125	48	90	44	61	105	68	21	13
Malaise
subjects affected / exposed	13 / 391 (3.32%)	11 / 391 (2.81%)	7 / 185 (3.78%)	17 / 387 (4.39%)	13 / 172 (7.56%)	11 / 183 (6.01%)	20 / 375 (5.33%)	24 / 371 (6.47%)	12 / 126 (9.52%)	13 / 123 (10.57%)
occurrences all number	16	14	9	29	27	16	36	29	16	23
Fatigue
subjects affected / exposed	88 / 391 (22.51%)	107 / 391 (27.37%)	38 / 185 (20.54%)	101 / 387 (26.10%)	54 / 172 (31.40%)	50 / 183 (27.32%)	87 / 375 (23.20%)	80 / 371 (21.56%)	18 / 126 (14.29%)	23 / 123 (18.70%)
occurrences all number	102	143	43	132	71	59	114	115	20	29
Chest pain
subjects affected / exposed	18 / 391 (4.60%)	19 / 391 (4.86%)	4 / 185 (2.16%)	13 / 387 (3.36%)	6 / 172 (3.49%)	12 / 183 (6.56%)	16 / 375 (4.27%)	14 / 371 (3.77%)	5 / 126 (3.97%)	3 / 123 (2.44%)
occurrences all number	19	20	4	13	7	14	17	15	5	3
Mucosal inflammation
subjects affected / exposed	12 / 391 (3.07%)	13 / 391 (3.32%)	3 / 185 (1.62%)	12 / 387 (3.10%)	13 / 172 (7.56%)	13 / 183 (7.10%)	19 / 375 (5.07%)	12 / 371 (3.23%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences all number	12	14	3	16	18	14	22	14	0	0
Pyrexia
subjects affected / exposed	57 / 391 (14.58%)	74 / 391 (18.93%)	32 / 185 (17.30%)	38 / 387 (9.82%)	33 / 172 (19.19%)	32 / 183 (17.49%)	54 / 375 (14.40%)	38 / 371 (10.24%)	40 / 126 (31.75%)	17 / 123 (13.82%)
occurrences all number	80	105	39	51	46	45	82	43	59	19
Pain
subjects affected / exposed	6 / 391 (1.53%)	6 / 391 (1.53%)	6 / 185 (3.24%)	6 / 387 (1.55%)	6 / 172 (3.49%)	4 / 183 (2.19%)	7 / 375 (1.87%)	4 / 371 (1.08%)	10 / 126 (7.94%)	4 / 123 (3.25%)
occurrences all number	6	6	6	6	6	4	7	4	10	6
Oedema peripheral
subjects affected / exposed	26 / 391 (6.65%)	49 / 391 (12.53%)	18 / 185 (9.73%)	37 / 387 (9.56%)	27 / 172 (15.70%)	23 / 183 (12.57%)	40 / 375 (10.67%)	38 / 371 (10.24%)	10 / 126 (7.94%)	4 / 123 (3.25%)
occurrences all number	28	55	21	44	32	26	50	42	12	4
Non-cardiac chest pain
subjects affected / exposed	20 / 391 (5.12%)	16 / 391 (4.09%)	17 / 185 (9.19%)	21 / 387 (5.43%)	9 / 172 (5.23%)	12 / 183 (6.56%)	18 / 375 (4.80%)	9 / 371 (2.43%)	15 / 126 (11.90%)	12 / 123 (9.76%)
occurrences all number	22	20	22	22	10	14	19	9	19	12
Respiratory, thoracic and mediastinal disorders
Hiccups
subjects affected / exposed	10 / 391 (2.56%)	7 / 391 (1.79%)	6 / 185 (3.24%)	20 / 387 (5.17%)	9 / 172 (5.23%)	14 / 183 (7.65%)	13 / 375 (3.47%)	13 / 371 (3.50%)	1 / 126 (0.79%)	6 / 123 (4.88%)
occurrences all number	11	7	9	22	21	20	17	15	2	10
Haemoptysis
subjects affected / exposed	26 / 391 (6.65%)	34 / 391 (8.70%)	17 / 185 (9.19%)	22 / 387 (5.68%)	9 / 172 (5.23%)	11 / 183 (6.01%)	19 / 375 (5.07%)	20 / 371 (5.39%)	31 / 126 (24.60%)	17 / 123 (13.82%)
occurrences all number	33	41	20	24	12	12	22	21	43	20
Epistaxis
subjects affected / exposed	9 / 391 (2.30%)	3 / 391 (0.77%)	3 / 185 (1.62%)	13 / 387 (3.36%)	9 / 172 (5.23%)	6 / 183 (3.28%)	11 / 375 (2.93%)	9 / 371 (2.43%)	3 / 126 (2.38%)	1 / 123 (0.81%)
occurrences all number	12	4	3	15	13	7	11	9	4	1
Dyspnoea
subjects affected / exposed	93 / 391 (23.79%)	98 / 391 (25.06%)	47 / 185 (25.41%)	61 / 387 (15.76%)	40 / 172 (23.26%)	39 / 183 (21.31%)	74 / 375 (19.73%)	55 / 371 (14.82%)	19 / 126 (15.08%)	16 / 123 (13.01%)
occurrences all number	106	111	53	68	47	45	80	58	20	16
Cough
subjects affected / exposed	82 / 391 (20.97%)	75 / 391 (19.18%)	31 / 185 (16.76%)	45 / 387 (11.63%)	45 / 172 (26.16%)	27 / 183 (14.75%)	69 / 375 (18.40%)	44 / 371 (11.86%)	30 / 126 (23.81%)	18 / 123 (14.63%)
occurrences all number	102	89	37	49	56	30	80	52	39	20
Pneumonitis
subjects affected / exposed	23 / 391 (5.88%)	22 / 391 (5.63%)	6 / 185 (3.24%)	3 / 387 (0.78%)	7 / 172 (4.07%)	1 / 183 (0.55%)	16 / 375 (4.27%)	1 / 371 (0.27%)	7 / 126 (5.56%)	0 / 123 (0.00%)
occurrences all number	31	24	9	3	7	1	19	1	8	0
Productive cough
subjects affected / exposed	30 / 391 (7.67%)	28 / 391 (7.16%)	12 / 185 (6.49%)	15 / 387 (3.88%)	11 / 172 (6.40%)	8 / 183 (4.37%)	24 / 375 (6.40%)	15 / 371 (4.04%)	15 / 126 (11.90%)	14 / 123 (11.38%)
occurrences all number	36	32	13	15	11	9	28	15	18	15
Psychiatric disorders
Insomnia
subjects affected / exposed	32 / 391 (8.18%)	43 / 391 (11.00%)	23 / 185 (12.43%)	30 / 387 (7.75%)	25 / 172 (14.53%)	11 / 183 (6.01%)	31 / 375 (8.27%)	23 / 371 (6.20%)	22 / 126 (17.46%)	11 / 123 (8.94%)
occurrences all number	33	45	31	34	27	12	37	26	31	23
Anxiety
subjects affected / exposed	12 / 391 (3.07%)	22 / 391 (5.63%)	5 / 185 (2.70%)	19 / 387 (4.91%)	7 / 172 (4.07%)	6 / 183 (3.28%)	9 / 375 (2.40%)	13 / 371 (3.50%)	1 / 126 (0.79%)	2 / 123 (1.63%)
occurrences all number	14	22	5	20	7	7	9	14	3	2
Investigations
Bilirubin conjugated increased
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	5 / 375 (1.33%)	0 / 371 (0.00%)	14 / 126 (11.11%)	3 / 123 (2.44%)
occurrences all number	0	0	0	0	0	0	7	0	28	3
Aspartate aminotransferase increased
subjects affected / exposed	37 / 391 (9.46%)	47 / 391 (12.02%)	27 / 185 (14.59%)	21 / 387 (5.43%)	16 / 172 (9.30%)	12 / 183 (6.56%)	48 / 375 (12.80%)	25 / 371 (6.74%)	46 / 126 (36.51%)	32 / 123 (26.02%)
occurrences all number	49	72	35	26	26	16	55	44	93	59
Amylase increased
subjects affected / exposed	22 / 391 (5.63%)	30 / 391 (7.67%)	18 / 185 (9.73%)	12 / 387 (3.10%)	17 / 172 (9.88%)	4 / 183 (2.19%)	33 / 375 (8.80%)	17 / 371 (4.58%)	24 / 126 (19.05%)	4 / 123 (3.25%)
occurrences all number	33	37	32	14	31	4	50	25	35	6
Alanine aminotransferase increased
subjects affected / exposed	40 / 391 (10.23%)	43 / 391 (11.00%)	31 / 185 (16.76%)	27 / 387 (6.98%)	22 / 172 (12.79%)	15 / 183 (8.20%)	48 / 375 (12.80%)	29 / 371 (7.82%)	42 / 126 (33.33%)	36 / 123 (29.27%)
occurrences all number	49	58	37	34	30	22	66	45	70	66
Blood alkaline phosphatase increased
subjects affected / exposed	13 / 391 (3.32%)	21 / 391 (5.37%)	13 / 185 (7.03%)	12 / 387 (3.10%)	7 / 172 (4.07%)	4 / 183 (2.19%)	23 / 375 (6.13%)	9 / 371 (2.43%)	18 / 126 (14.29%)	8 / 123 (6.50%)
occurrences all number	13	21	16	14	11	5	29	11	31	8
Blood glucose increased
subjects affected / exposed	2 / 391 (0.51%)	2 / 391 (0.51%)	1 / 185 (0.54%)	3 / 387 (0.78%)	1 / 172 (0.58%)	0 / 183 (0.00%)	5 / 375 (1.33%)	1 / 371 (0.27%)	7 / 126 (5.56%)	7 / 123 (5.69%)
occurrences all number	3	2	1	3	1	0	5	1	12	12
Blood lactate dehydrogenase increased
subjects affected / exposed	5 / 391 (1.28%)	3 / 391 (0.77%)	4 / 185 (2.16%)	4 / 387 (1.03%)	2 / 172 (1.16%)	2 / 183 (1.09%)	10 / 375 (2.67%)	5 / 371 (1.35%)	11 / 126 (8.73%)	8 / 123 (6.50%)
occurrences all number	5	3	5	4	3	2	22	5	16	11
Blood thyroid stimulating hormone decreased
subjects affected / exposed	3 / 391 (0.77%)	5 / 391 (1.28%)	2 / 185 (1.08%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	4 / 375 (1.07%)	0 / 371 (0.00%)	7 / 126 (5.56%)	0 / 123 (0.00%)
occurrences all number	3	5	2	0	1	0	5	0	9	0
Lipase increased
subjects affected / exposed	27 / 391 (6.91%)	31 / 391 (7.93%)	25 / 185 (13.51%)	14 / 387 (3.62%)	12 / 172 (6.98%)	1 / 183 (0.55%)	27 / 375 (7.20%)	16 / 371 (4.31%)	15 / 126 (11.90%)	6 / 123 (4.88%)
occurrences all number	49	44	38	14	16	2	44	27	29	9
Gamma-glutamyltransferase increased
subjects affected / exposed	7 / 391 (1.79%)	6 / 391 (1.53%)	5 / 185 (2.70%)	9 / 387 (2.33%)	2 / 172 (1.16%)	7 / 183 (3.83%)	17 / 375 (4.53%)	10 / 371 (2.70%)	23 / 126 (18.25%)	16 / 123 (13.01%)
occurrences all number	7	7	6	12	2	7	19	13	34	18
Blood creatinine increased
subjects affected / exposed	15 / 391 (3.84%)	23 / 391 (5.88%)	13 / 185 (7.03%)	21 / 387 (5.43%)	18 / 172 (10.47%)	10 / 183 (5.46%)	41 / 375 (10.93%)	29 / 371 (7.82%)	13 / 126 (10.32%)	11 / 123 (8.94%)
occurrences all number	23	39	26	26	34	15	72	38	29	12
Blood bilirubin increased
subjects affected / exposed	5 / 391 (1.28%)	5 / 391 (1.28%)	3 / 185 (1.62%)	3 / 387 (0.78%)	0 / 172 (0.00%)	2 / 183 (1.09%)	9 / 375 (2.40%)	0 / 371 (0.00%)	23 / 126 (18.25%)	10 / 123 (8.13%)
occurrences all number	6	7	3	3	0	3	13	0	44	17
Blood thyroid stimulating hormone increased
subjects affected / exposed	6 / 391 (1.53%)	10 / 391 (2.56%)	3 / 185 (1.62%)	3 / 387 (0.78%)	4 / 172 (2.33%)	1 / 183 (0.55%)	5 / 375 (1.33%)	1 / 371 (0.27%)	7 / 126 (5.56%)	1 / 123 (0.81%)
occurrences all number	7	10	5	5	5	1	5	1	7	1
Lymphocyte count decreased
subjects affected / exposed	4 / 391 (1.02%)	7 / 391 (1.79%)	2 / 185 (1.08%)	9 / 387 (2.33%)	8 / 172 (4.65%)	4 / 183 (2.19%)	3 / 375 (0.80%)	3 / 371 (0.81%)	10 / 126 (7.94%)	9 / 123 (7.32%)
occurrences all number	4	9	11	13	27	5	3	4	25	20
Neutrophil count decreased
subjects affected / exposed	11 / 391 (2.81%)	9 / 391 (2.30%)	2 / 185 (1.08%)	50 / 387 (12.92%)	31 / 172 (18.02%)	20 / 183 (10.93%)	52 / 375 (13.87%)	54 / 371 (14.56%)	16 / 126 (12.70%)	54 / 123 (43.90%)
occurrences all number	14	26	5	100	56	45	146	135	34	170
Neutrophil count increased
subjects affected / exposed	1 / 391 (0.26%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	4 / 375 (1.07%)	1 / 371 (0.27%)	8 / 126 (6.35%)	3 / 123 (2.44%)
occurrences all number	1	1	0	0	0	0	6	1	11	3
Platelet count decreased
subjects affected / exposed	10 / 391 (2.56%)	6 / 391 (1.53%)	2 / 185 (1.08%)	31 / 387 (8.01%)	22 / 172 (12.79%)	25 / 183 (13.66%)	38 / 375 (10.13%)	30 / 371 (8.09%)	22 / 126 (17.46%)	49 / 123 (39.84%)
occurrences all number	19	12	4	43	44	41	75	54	28	96
Weight decreased
subjects affected / exposed	20 / 391 (5.12%)	37 / 391 (9.46%)	17 / 185 (9.19%)	22 / 387 (5.68%)	14 / 172 (8.14%)	8 / 183 (4.37%)	32 / 375 (8.53%)	31 / 371 (8.36%)	44 / 126 (34.92%)	19 / 123 (15.45%)
occurrences all number	24	42	21	24	14	8	33	35	55	21
Weight increased
subjects affected / exposed	8 / 391 (2.05%)	8 / 391 (2.05%)	1 / 185 (0.54%)	3 / 387 (0.78%)	3 / 172 (1.74%)	1 / 183 (0.55%)	10 / 375 (2.67%)	3 / 371 (0.81%)	7 / 126 (5.56%)	10 / 123 (8.13%)
occurrences all number	9	8	2	3	4	1	11	3	10	11
White blood cell count decreased
subjects affected / exposed	5 / 391 (1.28%)	8 / 391 (2.05%)	1 / 185 (0.54%)	19 / 387 (4.91%)	17 / 172 (9.88%)	6 / 183 (3.28%)	41 / 375 (10.93%)	39 / 371 (10.51%)	22 / 126 (17.46%)	59 / 123 (47.97%)
occurrences all number	7	15	1	39	39	9	132	100	36	186
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	6 / 391 (1.53%)	12 / 391 (3.07%)	3 / 185 (1.62%)	2 / 387 (0.52%)	10 / 172 (5.81%)	1 / 183 (0.55%)	8 / 375 (2.13%)	5 / 371 (1.35%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences all number	7	13	3	2	13	2	8	5	0	0
Nervous system disorders
Dysgeusia
subjects affected / exposed	10 / 391 (2.56%)	14 / 391 (3.58%)	5 / 185 (2.70%)	25 / 387 (6.46%)	11 / 172 (6.40%)	9 / 183 (4.92%)	17 / 375 (4.53%)	14 / 371 (3.77%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences all number	10	16	6	26	12	10	18	15	0	0
Dizziness
subjects affected / exposed	21 / 391 (5.37%)	30 / 391 (7.67%)	16 / 185 (8.65%)	27 / 387 (6.98%)	18 / 172 (10.47%)	21 / 183 (11.48%)	31 / 375 (8.27%)	18 / 371 (4.85%)	16 / 126 (12.70%)	10 / 123 (8.13%)
occurrences all number	22	32	16	32	22	26	33	18	22	14
Headache
subjects affected / exposed	40 / 391 (10.23%)	54 / 391 (13.81%)	13 / 185 (7.03%)	31 / 387 (8.01%)	19 / 172 (11.05%)	8 / 183 (4.37%)	34 / 375 (9.07%)	24 / 371 (6.47%)	12 / 126 (9.52%)	8 / 123 (6.50%)
occurrences all number	46	72	15	33	25	13	44	33	21	8
Neuropathy peripheral
subjects affected / exposed	5 / 391 (1.28%)	1 / 391 (0.26%)	2 / 185 (1.08%)	11 / 387 (2.84%)	4 / 172 (2.33%)	3 / 183 (1.64%)	26 / 375 (6.93%)	12 / 371 (3.23%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences all number	6	1	2	13	4	3	27	12	1	0
Paraesthesia
subjects affected / exposed	2 / 391 (0.51%)	14 / 391 (3.58%)	4 / 185 (2.16%)	9 / 387 (2.33%)	10 / 172 (5.81%)	5 / 183 (2.73%)	19 / 375 (5.07%)	16 / 371 (4.31%)	0 / 126 (0.00%)	0 / 123 (0.00%)
occurrences all number	2	16	4	10	11	5	20	16	0	0
Blood and lymphatic system disorders
Leukopenia
subjects affected / exposed	3 / 391 (0.77%)	0 / 391 (0.00%)	1 / 185 (0.54%)	21 / 387 (5.43%)	10 / 172 (5.81%)	9 / 183 (4.92%)	19 / 375 (5.07%)	15 / 371 (4.04%)	5 / 126 (3.97%)	25 / 123 (20.33%)
occurrences all number	3	0	1	32	21	16	41	30	9	77
Neutropenia
subjects affected / exposed	7 / 391 (1.79%)	4 / 391 (1.02%)	2 / 185 (1.08%)	70 / 387 (18.09%)	45 / 172 (26.16%)	37 / 183 (20.22%)	66 / 375 (17.60%)	58 / 371 (15.63%)	2 / 126 (1.59%)	16 / 123 (13.01%)
occurrences all number	9	5	2	110	80	62	125	103	6	36
Anaemia
subjects affected / exposed	51 / 391 (13.04%)	47 / 391 (12.02%)	25 / 185 (13.51%)	159 / 387 (41.09%)	80 / 172 (46.51%)	76 / 183 (41.53%)	174 / 375 (46.40%)	151 / 371 (40.70%)	63 / 126 (50.00%)	93 / 123 (75.61%)
occurrences all number	76	69	37	199	123	93	273	202	125	167
Leukocytosis
subjects affected / exposed	4 / 391 (1.02%)	6 / 391 (1.53%)	4 / 185 (2.16%)	1 / 387 (0.26%)	1 / 172 (0.58%)	1 / 183 (0.55%)	4 / 375 (1.07%)	4 / 371 (1.08%)	9 / 126 (7.14%)	4 / 123 (3.25%)
occurrences all number	4	6	4	1	1	1	4	5	12	4
Thrombocytopenia
subjects affected / exposed	7 / 391 (1.79%)	6 / 391 (1.53%)	2 / 185 (1.08%)	39 / 387 (10.08%)	17 / 172 (9.88%)	14 / 183 (7.65%)	48 / 375 (12.80%)	31 / 371 (8.36%)	2 / 126 (1.59%)	14 / 123 (11.38%)
occurrences all number	7	8	2	60	27	21	85	42	4	38
Eye disorders
Lacrimation increased
subjects affected / exposed	1 / 391 (0.26%)	3 / 391 (0.77%)	1 / 185 (0.54%)	18 / 387 (4.65%)	9 / 172 (5.23%)	2 / 183 (1.09%)	20 / 375 (5.33%)	10 / 371 (2.70%)	0 / 126 (0.00%)	1 / 123 (0.81%)
occurrences all number	1	4	1	18	11	2	22	10	0	1
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	30 / 391 (7.67%)	30 / 391 (7.67%)	9 / 185 (4.86%)	21 / 387 (5.43%)	10 / 172 (5.81%)	7 / 183 (3.83%)	30 / 375 (8.00%)	15 / 371 (4.04%)	7 / 126 (5.56%)	4 / 123 (3.25%)
occurrences all number	37	36	11	24	11	7	41	16	8	7
Abdominal pain upper
subjects affected / exposed	16 / 391 (4.09%)	18 / 391 (4.60%)	4 / 185 (2.16%)	22 / 387 (5.68%)	5 / 172 (2.91%)	6 / 183 (3.28%)	22 / 375 (5.87%)	13 / 371 (3.50%)	8 / 126 (6.35%)	2 / 123 (1.63%)
occurrences all number	18	19	4	25	5	8	27	16	12	2
Constipation
subjects affected / exposed	70 / 391 (17.90%)	78 / 391 (19.95%)	36 / 185 (19.46%)	104 / 387 (26.87%)	63 / 172 (36.63%)	53 / 183 (28.96%)	84 / 375 (22.40%)	83 / 371 (22.37%)	20 / 126 (15.87%)	25 / 123 (20.33%)
occurrences all number	78	96	47	146	86	66	110	119	23	39
Diarrhoea
subjects affected / exposed	88 / 391 (22.51%)	102 / 391 (26.09%)	44 / 185 (23.78%)	66 / 387 (17.05%)	38 / 172 (22.09%)	33 / 183 (18.03%)	79 / 375 (21.07%)	48 / 371 (12.94%)	26 / 126 (20.63%)	8 / 123 (6.50%)
occurrences all number	142	178	70	80	55	46	121	71	35	12
Dry mouth
subjects affected / exposed	11 / 391 (2.81%)	17 / 391 (4.35%)	6 / 185 (3.24%)	3 / 387 (0.78%)	2 / 172 (1.16%)	0 / 183 (0.00%)	11 / 375 (2.93%)	5 / 371 (1.35%)	8 / 126 (6.35%)	0 / 123 (0.00%)
occurrences all number	11	19	8	3	2	0	11	5	8	0
Dyspepsia
subjects affected / exposed	10 / 391 (2.56%)	15 / 391 (3.84%)	7 / 185 (3.78%)	10 / 387 (2.58%)	13 / 172 (7.56%)	6 / 183 (3.28%)	12 / 375 (3.20%)	8 / 371 (2.16%)	2 / 126 (1.59%)	0 / 123 (0.00%)
occurrences all number	11	18	7	28	16	6	12	11	2	0
Mouth ulceration
subjects affected / exposed	0 / 391 (0.00%)	4 / 391 (1.02%)	0 / 185 (0.00%)	3 / 387 (0.78%)	0 / 172 (0.00%)	0 / 183 (0.00%)	2 / 375 (0.53%)	2 / 371 (0.54%)	8 / 126 (6.35%)	1 / 123 (0.81%)
occurrences all number	0	4	0	4	0	0	2	2	9	1
Stomatitis
subjects affected / exposed	12 / 391 (3.07%)	25 / 391 (6.39%)	2 / 185 (1.08%)	28 / 387 (7.24%)	16 / 172 (9.30%)	11 / 183 (6.01%)	17 / 375 (4.53%)	10 / 371 (2.70%)	1 / 126 (0.79%)	3 / 123 (2.44%)
occurrences all number	17	29	2	37	22	11	19	12	2	3
Vomiting
subjects affected / exposed	41 / 391 (10.49%)	52 / 391 (13.30%)	27 / 185 (14.59%)	73 / 387 (18.86%)	33 / 172 (19.19%)	34 / 183 (18.58%)	55 / 375 (14.67%)	56 / 371 (15.09%)	20 / 126 (15.87%)	25 / 123 (20.33%)
occurrences all number	64	72	46	109	50	50	81	79	25	45
Nausea
subjects affected / exposed	81 / 391 (20.72%)	93 / 391 (23.79%)	41 / 185 (22.16%)	174 / 387 (44.96%)	79 / 172 (45.93%)	74 / 183 (40.44%)	126 / 375 (33.60%)	133 / 371 (35.85%)	17 / 126 (13.49%)	30 / 123 (24.39%)
occurrences all number	104	130	66	319	145	118	203	220	18	59
Hepatobiliary disorders
Hepatic function abnormal
subjects affected / exposed	0 / 391 (0.00%)	3 / 391 (0.77%)	1 / 185 (0.54%)	1 / 387 (0.26%)	2 / 172 (1.16%)	2 / 183 (1.09%)	3 / 375 (0.80%)	2 / 371 (0.54%)	8 / 126 (6.35%)	9 / 123 (7.32%)
occurrences all number	0	4	1	1	2	3	3	2	15	9
Skin and subcutaneous tissue disorders
Rash maculo-papular
subjects affected / exposed	13 / 391 (3.32%)	28 / 391 (7.16%)	14 / 185 (7.57%)	7 / 387 (1.81%)	9 / 172 (5.23%)	4 / 183 (2.19%)	10 / 375 (2.67%)	4 / 371 (1.08%)	5 / 126 (3.97%)	2 / 123 (1.63%)
occurrences all number	15	35	26	10	15	4	10	4	8	2
Rash
subjects affected / exposed	55 / 391 (14.07%)	93 / 391 (23.79%)	31 / 185 (16.76%)	31 / 387 (8.01%)	29 / 172 (16.86%)	13 / 183 (7.10%)	59 / 375 (15.73%)	32 / 371 (8.63%)	32 / 126 (25.40%)	15 / 123 (12.20%)
occurrences all number	71	136	38	33	40	16	75	33	41	17
Dry skin
subjects affected / exposed	14 / 391 (3.58%)	37 / 391 (9.46%)	9 / 185 (4.86%)	12 / 387 (3.10%)	11 / 172 (6.40%)	4 / 183 (2.19%)	7 / 375 (1.87%)	9 / 371 (2.43%)	1 / 126 (0.79%)	1 / 123 (0.81%)
occurrences all number	14	43	13	12	11	4	7	9	1	1
Alopecia
subjects affected / exposed	9 / 391 (2.30%)	8 / 391 (2.05%)	3 / 185 (1.62%)	34 / 387 (8.79%)	12 / 172 (6.98%)	10 / 183 (5.46%)	45 / 375 (12.00%)	45 / 371 (12.13%)	3 / 126 (2.38%)	5 / 123 (4.07%)
occurrences all number	9	8	3	34	12	11	47	47	3	5
Pruritus
subjects affected / exposed	44 / 391 (11.25%)	92 / 391 (23.53%)	29 / 185 (15.68%)	17 / 387 (4.39%)	23 / 172 (13.37%)	5 / 183 (2.73%)	38 / 375 (10.13%)	11 / 371 (2.96%)	27 / 126 (21.43%)	5 / 123 (4.07%)
occurrences all number	49	122	45	20	28	6	43	11	39	5
Endocrine disorders
Hypothyroidism
subjects affected / exposed	30 / 391 (7.67%)	61 / 391 (15.60%)	22 / 185 (11.89%)	4 / 387 (1.03%)	9 / 172 (5.23%)	1 / 183 (0.55%)	33 / 375 (8.80%)	4 / 371 (1.08%)	27 / 126 (21.43%)	3 / 123 (2.44%)
occurrences all number	38	65	25	5	10	1	35	7	32	3
Hyperthyroidism
subjects affected / exposed	18 / 391 (4.60%)	33 / 391 (8.44%)	19 / 185 (10.27%)	7 / 387 (1.81%)	9 / 172 (5.23%)	0 / 183 (0.00%)	11 / 375 (2.93%)	6 / 371 (1.62%)	20 / 126 (15.87%)	3 / 123 (2.44%)
occurrences all number	18	34	19	7	10	0	11	6	24	3
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	24 / 391 (6.14%)	17 / 391 (4.35%)	7 / 185 (3.78%)	10 / 387 (2.58%)	14 / 172 (8.14%)	4 / 183 (2.19%)	25 / 375 (6.67%)	21 / 371 (5.66%)	7 / 126 (5.56%)	4 / 123 (3.25%)
occurrences all number	25	21	7	13	18	4	29	22	8	4
Myalgia
subjects affected / exposed	22 / 391 (5.63%)	23 / 391 (5.88%)	9 / 185 (4.86%)	9 / 387 (2.33%)	10 / 172 (5.81%)	3 / 183 (1.64%)	30 / 375 (8.00%)	21 / 371 (5.66%)	1 / 126 (0.79%)	0 / 123 (0.00%)
occurrences all number	28	24	9	10	10	3	37	24	1	0
Back pain
subjects affected / exposed	36 / 391 (9.21%)	42 / 391 (10.74%)	28 / 185 (15.14%)	31 / 387 (8.01%)	23 / 172 (13.37%)	13 / 183 (7.10%)	38 / 375 (10.13%)	29 / 371 (7.82%)	10 / 126 (7.94%)	11 / 123 (8.94%)
occurrences all number	41	48	33	33	31	14	51	31	12	11
Arthralgia
subjects affected / exposed	62 / 391 (15.86%)	72 / 391 (18.41%)	26 / 185 (14.05%)	19 / 387 (4.91%)	28 / 172 (16.28%)	9 / 183 (4.92%)	40 / 375 (10.67%)	40 / 371 (10.78%)	17 / 126 (13.49%)	7 / 123 (5.69%)
occurrences all number	77	93	30	22	31	10	51	48	21	7
Infections and infestations
Bronchitis
subjects affected / exposed	11 / 391 (2.81%)	17 / 391 (4.35%)	9 / 185 (4.86%)	9 / 387 (2.33%)	9 / 172 (5.23%)	8 / 183 (4.37%)	18 / 375 (4.80%)	7 / 371 (1.89%)	2 / 126 (1.59%)	0 / 123 (0.00%)
occurrences all number	12	18	11	12	14	9	25	10	2	0
Nasopharyngitis
subjects affected / exposed	23 / 391 (5.88%)	27 / 391 (6.91%)	9 / 185 (4.86%)	22 / 387 (5.68%)	15 / 172 (8.72%)	4 / 183 (2.19%)	14 / 375 (3.73%)	12 / 371 (3.23%)	1 / 126 (0.79%)	1 / 123 (0.81%)
occurrences all number	32	33	13	26	18	5	18	13	2	1
Upper respiratory tract infection
subjects affected / exposed	17 / 391 (4.35%)	14 / 391 (3.58%)	7 / 185 (3.78%)	12 / 387 (3.10%)	14 / 172 (8.14%)	6 / 183 (3.28%)	25 / 375 (6.67%)	14 / 371 (3.77%)	16 / 126 (12.70%)	11 / 123 (8.94%)
occurrences all number	23	17	9	15	18	6	34	28	16	22
Pneumonia
subjects affected / exposed	20 / 391 (5.12%)	21 / 391 (5.37%)	12 / 185 (6.49%)	17 / 387 (4.39%)	10 / 172 (5.81%)	7 / 183 (3.83%)	23 / 375 (6.13%)	27 / 371 (7.28%)	16 / 126 (12.70%)	11 / 123 (8.94%)
occurrences all number	22	23	15	20	12	9	27	30	20	11
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	97 / 391 (24.81%)	130 / 391 (33.25%)	61 / 185 (32.97%)	109 / 387 (28.17%)	61 / 172 (35.47%)	52 / 183 (28.42%)	105 / 375 (28.00%)	88 / 371 (23.72%)	40 / 126 (31.75%)	34 / 123 (27.64%)
occurrences all number	119	174	64	161	85	65	128	114	53	55
Hyperglycaemia
subjects affected / exposed	16 / 391 (4.09%)	24 / 391 (6.14%)	9 / 185 (4.86%)	14 / 387 (3.62%)	6 / 172 (3.49%)	9 / 183 (4.92%)	29 / 375 (7.73%)	20 / 371 (5.39%)	18 / 126 (14.29%)	13 / 123 (10.57%)
occurrences all number	20	30	13	15	11	13	44	25	24	26
Hyperkalaemia
subjects affected / exposed	12 / 391 (3.07%)	10 / 391 (2.56%)	6 / 185 (3.24%)	9 / 387 (2.33%)	11 / 172 (6.40%)	3 / 183 (1.64%)	12 / 375 (3.20%)	11 / 371 (2.96%)	6 / 126 (4.76%)	5 / 123 (4.07%)
occurrences all number	15	13	6	13	26	7	18	13	7	5
Hyponatraemia
subjects affected / exposed	17 / 391 (4.35%)	39 / 391 (9.97%)	14 / 185 (7.57%)	20 / 387 (5.17%)	11 / 172 (6.40%)	8 / 183 (4.37%)	25 / 375 (6.67%)	16 / 371 (4.31%)	47 / 126 (37.30%)	18 / 123 (14.63%)
occurrences all number	19	59	21	24	20	10	39	19	81	26
Hypomagnesaemia
subjects affected / exposed	7 / 391 (1.79%)	12 / 391 (3.07%)	10 / 185 (5.41%)	21 / 387 (5.43%)	15 / 172 (8.72%)	12 / 183 (6.56%)	25 / 375 (6.67%)	22 / 371 (5.93%)	10 / 126 (7.94%)	6 / 123 (4.88%)
occurrences all number	15	14	13	30	22	12	39	26	15	11
Hypokalaemia
subjects affected / exposed	16 / 391 (4.09%)	27 / 391 (6.91%)	13 / 185 (7.03%)	12 / 387 (3.10%)	13 / 172 (7.56%)	9 / 183 (4.92%)	27 / 375 (7.20%)	21 / 371 (5.66%)	24 / 126 (19.05%)	11 / 123 (8.94%)
occurrences all number	26	33	29	13	14	14	39	26	37	14
Hypochloraemia
subjects affected / exposed	0 / 391 (0.00%)	1 / 391 (0.26%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	5 / 375 (1.33%)	1 / 371 (0.27%)	17 / 126 (13.49%)	9 / 123 (7.32%)
occurrences all number	0	1	0	0	1	0	7	1	25	12
Hypermagnesaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	2 / 387 (0.52%)	0 / 172 (0.00%)	0 / 183 (0.00%)	0 / 375 (0.00%)	0 / 371 (0.00%)	7 / 126 (5.56%)	2 / 123 (1.63%)
occurrences all number	0	0	0	2	0	0	0	0	11	2
Hypoalbuminaemia
subjects affected / exposed	16 / 391 (4.09%)	25 / 391 (6.39%)	9 / 185 (4.86%)	14 / 387 (3.62%)	8 / 172 (4.65%)	7 / 183 (3.83%)	25 / 375 (6.67%)	15 / 371 (4.04%)	41 / 126 (32.54%)	20 / 123 (16.26%)
occurrences all number	17	33	17	17	14	7	29	23	71	39
Hyperuricaemia
subjects affected / exposed	3 / 391 (0.77%)	1 / 391 (0.26%)	2 / 185 (1.08%)	1 / 387 (0.26%)	1 / 172 (0.58%)	2 / 183 (1.09%)	7 / 375 (1.87%)	7 / 371 (1.89%)	20 / 126 (15.87%)	9 / 123 (7.32%)
occurrences all number	3	1	3	2	1	2	14	8	51	15
Hypertriglyceridaemia
subjects affected / exposed	1 / 391 (0.26%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	0 / 172 (0.00%)	0 / 183 (0.00%)	1 / 375 (0.27%)	1 / 371 (0.27%)	8 / 126 (6.35%)	9 / 123 (7.32%)
occurrences all number	1	0	0	0	0	0	1	1	21	12
Hypocalcaemia
subjects affected / exposed	9 / 391 (2.30%)	12 / 391 (3.07%)	5 / 185 (2.70%)	9 / 387 (2.33%)	7 / 172 (4.07%)	3 / 183 (1.64%)	7 / 375 (1.87%)	6 / 371 (1.62%)	14 / 126 (11.11%)	8 / 123 (6.50%)
occurrences all number	11	13	5	13	7	4	9	7	23	9
Hypoproteinaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 391 (0.00%)	0 / 185 (0.00%)	0 / 387 (0.00%)	1 / 172 (0.58%)	0 / 183 (0.00%)	1 / 375 (0.27%)	3 / 371 (0.81%)	15 / 126 (11.90%)	14 / 123 (11.38%)
occurrences all number	0	0	0	0	1	0	1	3	24	20
Hypophosphataemia
subjects affected / exposed	10 / 391 (2.56%)	14 / 391 (3.58%)	5 / 185 (2.70%)	11 / 387 (2.84%)	7 / 172 (4.07%)	5 / 183 (2.73%)	10 / 375 (2.67%)	8 / 371 (2.16%)	8 / 126 (6.35%)	2 / 123 (1.63%)
occurrences all number	16	20	9	13	9	7	16	8	13	3

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Were there any global substantial amendments to the protocol? Yes

21 Oct 2015

Replacement of Arm E (nivolumab 1 mg/kg Q2W + ipilimumab 1 mg/kg Q6W) with Arm G (nivolumab + chemotherapy) in Part 1b (PD-L1 < 1% subjects). Defined programmed cell death ligand 1 (PD-L1 1%) NSCLC subjects as ‘PD-L1 expressing NSCLC subjects’ and PD-L1 (< 1%) NSCLC subjects as ‘PD-L1 non-expressing NSCLC subjects.’ Updated CA209012 data in background sections. Clarified the target population, added dose details for carboplatin when treated with gemcitabine or pemetrexed, clarified aspartate aminotransferase(AST)/alanine aminotransferase(ALT) values when liver metastases were present, and removed cytochrome P450 (CYP)3A4 language throughout the protocol.

17 Nov 2016

Changes in Part1a (PD-L1 ≥ 1%) Single primary end-point OS for nivolumab +ipilimumabvs chemotherapyin PD-L1≥50% (OS PD-L1≥1% next in hierarchy) Demotion of PFS to secondary end-points Demotion of nivolumabvs chemotherapycomparisons to secondary end-point Increased the sample size from 990 to 1200 to ensure at least 400 subjects with PD-L1 ≥50% were available for the primary endpoint, based on the expected distribution of PD-L1 in first-line NSLC Changes in Part 1b (PD-L1 < 1%) Single primary endpoint of PFS nivolumabvs chemotherapyvs chemotherapy Demotednivolumab +ipilimumabvs chemotherapyendpoints and OSand PFS fornivolumabvs chemotherapyvs chemotherapyto secondary Decreasedsample size to conclude enrolment together with PD-L1≥1% and allowedaddition of Part 2 (nivolumabvs chemotherapyvs chemotherapyin all comers)

27 Jun 2017

Increased enrolled subjects from 739 to 1153 and increased randomized subjects from 480 to approximately 750 for Part 2 only and modified the statistical considerations and sample size justifications accordingly.

05 Oct 2017

In May-2017, prior to BMS’s decision to amend the CA209227 protocol, preliminary efficacy by TMB results (F1CDx) became available from CA209568 (nivo + ipi). CA209568 studied the same combination dose and regimen (nivolumab 3mg/kg Q2W + ipilimumab 1 mg/kg Q6W) and patient population as CA209227. CA209568 also demonstrated that a clinically meaningful cutoff could be determined to identify the group of patients most likely to benefit from combination immunotherapy over first-line chemotherapy.

01 Jun 2018

Removed 1 of the 2 interim OS analyses in Part 2, because emerging data with chemo + PD-1 inhibitors showed a consistent delayed benefit, with immuno-oncology (IO)mechanism of action (more pronounced in patients with low or no PD-L1 expressing tumors). Given that there are close to 50% of subjects with PD-L1 non-expressing tumors in Part 2, early evaluation of OS may miss detecting the benefit in terms of OS drivenby nivolumab +chemotherapy. Subjects with squamous histology were enrolled, and in the absence of any survival data with chemo+PD-L1, early evaluation of OS may not be appropriate.

15 Aug 2018

The main purpose of the Amendment is to adapt the analyses of Part 2 of CA209227 to evolving science, in order to better demonstrate the benefit of nivolumab +chemotherapy in subjects with non-squamous histology subtype NSCLC in the first-line setting.

Were there any global interruptions to the trial? No

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

None reported

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Clinical Trial Results:
An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)

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Primary: Progression-Free Survival per BICR

Primary: Progression-Free Survival per BICR

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Primary: Overall Survival

Secondary: Objective Response Rate (ORR) per BICR

Secondary: Objective Response Rate (ORR) per BICR

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Secondary: Percentage of Participants with Symptom Deterioration at Week 12 assessed via Lung Cancer Symptom Scale

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Clinical trials

Clinical Trial Results: An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)

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Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

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Primary: Progression-Free Survival per BICR

Primary: Progression-Free Survival per BICR

Primary: Overall Survival

Primary: Overall Survival

Secondary: Objective Response Rate (ORR) per BICR

Secondary: Objective Response Rate (ORR) per BICR

Secondary: Percentage of Participants with Symptom Deterioration at Week 12 assessed via Lung Cancer Symptom Scale

Secondary: Percentage of Participants with Symptom Deterioration at Week 12 assessed via Lung Cancer Symptom Scale

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)