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Clinical Trial Results:
A facilitated access program to provide Everolimus (RAD) for maintenance for patients completing therapy in RAD trials in solid organ transplantation

Summary
EudraCT number	2004-001473-25
Trial protocol	BE GB
Global end of trial date	14 Feb 2014

Results information
Results version number	v1(current)
This version publication date	19 Mar 2020
First version publication date	19 Mar 2020
Other versions

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

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Trial information

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Sponsor protocol code

CRAD001A2401

ISRCTN number

-

US NCT number

NCT00149981

WHO universal trial number (UTN)

-

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharmaceuticals AG, 41 613241111,

Scientific contact

Clinical Disclosure Office, Novartis Pharmaceuticals AG, 41 613241111,

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

No

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

No

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

No

Analysis stage

Final

Date of interim/final analysis

14 Feb 2014

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

14 Feb 2014

Was the trial ended prematurely?

No

Main objective of the trial

• To facilitate the management of patients on maintenance immunosuppression therapy who are completing everolimus trials, • To provide everolimus maintenance therapy through this access program and • To collect and review safety data for up to 120 months or until the project has been discontinued whichever comes first. • To collect and review safety data for up to 120 months or when Certican is commercially available in the given indication and reimbursed by appropriate payors or the project has been discontinued, whichever comes first.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

13 Aug 2003

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

No

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 13

Country: Number of subjects enrolled

Belgium: 11

Country: Number of subjects enrolled

Germany: 12

Country: Number of subjects enrolled

Spain: 20

Country: Number of subjects enrolled

United States: 494

Country: Number of subjects enrolled

Australia: 34

Country: Number of subjects enrolled

Brazil: 98

Country: Number of subjects enrolled

Canada: 79

Country: Number of subjects enrolled

Czech Republic: 28

Country: Number of subjects enrolled

France: 61

Country: Number of subjects enrolled

Italy: 82

Country: Number of subjects enrolled

New Zealand: 12

Country: Number of subjects enrolled

Norway: 9

Country: Number of subjects enrolled

Poland: 4

Country: Number of subjects enrolled

Russian Federation: 5

Country: Number of subjects enrolled

South Africa: 8

Country: Number of subjects enrolled

Switzerland: 7

Country: Number of subjects enrolled

Taiwan: 47

Worldwide total number of subjects

1024

EEA total number of subjects

240

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

9

Adolescents (12-17 years)

9

Adults (18-64 years)

908

From 65 to 84 years

98

85 years and over

0

Subject disposition

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Recruitment details

-

Screening details

Approximately 1000 adult (kidney, pancreas, heart, liver, or lung) and pediatric transplant patients at around 500 sites who were previously enrolled and were in the follow-up phases in Novartis transplant trials were planned for enrollment in this study.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Renal - Adult Patients

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Everolimus

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Everolimus was provided in blister packs as 0.25 mg, 0.5 mg and 0.75 mg tablets. For pediatric patients who do not swallow tablets, a fast-dispersible tablet formulation of 0.25 mg nd 0.1 mg was provided.

Pancreas- Kidney - Adult Patients

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Everolimus

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Everolimus was provided in blister packs as 0.25 mg, 0.5 mg and 0.75 mg tablets. For pediatric patients who do not swallow tablets, a fast-dispersible tablet formulation of 0.25 mg nd 0.1 mg was provided.

Liver - Adult Patients

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Everolimus

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Everolimus was provided in blister packs as 0.25 mg, 0.5 mg and 0.75 mg tablets. For pediatric patients who do not swallow tablets, a fast-dispersible tablet formulation of 0.25 mg nd 0.1 mg was provided.

Heart - Adult Patients

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Everolimus

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Everolimus was provided in blister packs as 0.25 mg, 0.5 mg and 0.75 mg tablets. For pediatric patients who do not swallow tablets, a fast-dispersible tablet formulation of 0.25 mg nd 0.1 mg was provided.

Lung/ Heart- Lung - Adult Patients

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Everolimus

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Everolimus was provided in blister packs as 0.25 mg, 0.5 mg and 0.75 mg tablets. For pediatric patients who do not swallow tablets, a fast-dispersible tablet formulation of 0.25 mg nd 0.1 mg was provided.

Renal - Pediatric

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Everolimus

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Everolimus was provided in blister packs as 0.25 mg, 0.5 mg and 0.75 mg tablets. For pediatric patients who do not swallow tablets, a fast-dispersible tablet formulation of 0.25 mg nd 0.1 mg was provided.

Number of subjects in period 1	Renal - Adult Patients	Pancreas- Kidney - Adult Patients	Liver - Adult Patients	Heart - Adult Patients	Lung/ Heart- Lung - Adult Patients	Renal - Pediatric
Started	701	8	18	254	24	19
Completed	482	4	8	167	12	5
Not completed	219	4	10	87	12	14
Patient Withdrew Consent	17	-	-	-	-	-
Consent withdrawn by subject	-	-	-	7	-	-
Adverse event, non-fatal	98	3	4	31	3	2
Death	24	-	1	20	3	-
Abnormal Laboratory Value(s)	8	1	-	2	-	-
Unsatisfactory Therapeutic Effect	10	-	-	-	-	1
Administrative Problems	16	-	-	11	2	10
Protocol Violation	1	-	-	4	-	-
Abnormal Test Procedure Result(s)	1	-	-	2	-	1
Patient's Condition No Longer Requires Study Drug	5	-	1	1	1	-
Lost to follow-up	12	-	2	6	-	-
Missing	27	-	2	3	3	-

Baseline characteristics

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Reporting group title

Renal - Adult Patients

Reporting group description

-

Reporting group title

Pancreas- Kidney - Adult Patients

Reporting group description

-

Reporting group title

Liver - Adult Patients

Reporting group description

-

Reporting group title

Heart - Adult Patients

Reporting group description

-

Reporting group title

Lung/ Heart- Lung - Adult Patients

Reporting group description

-

Reporting group title

Renal - Pediatric

Reporting group description

-

Reporting group values	Renal - Adult Patients	Pancreas- Kidney - Adult Patients	Liver - Adult Patients	Heart - Adult Patients	Lung/ Heart- Lung - Adult Patients	Renal - Pediatric	Total
Number of subjects	701	8	18	254	24	19	1024
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	9	9
Adolescents (12-17 years)	0	0	0	0	0	9	9
Adults (18-64 years)	651	8	18	208	22	1	908
From 65-84 years	50	0	0	46	2	0	98
85 years and over	0	0	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	48.0 ( 11.69 )	40.5 ( 4.57 )	47.1 ( 11.71 )	53.3 ( 11.61 )	50.1 ( 12.35 )	11.2 ( 4.67 )	-
Gender categorical
Units: Subjects
Female	227	4	10	53	8	6	308
Male	474	4	8	201	16	13	716

End points

Top of page

Reporting group title

Renal - Adult Patients

Reporting group description

-

Reporting group title

Pancreas- Kidney - Adult Patients

Reporting group description

-

Reporting group title

Liver - Adult Patients

Reporting group description

-

Reporting group title

Heart - Adult Patients

Reporting group description

-

Reporting group title

Lung/ Heart- Lung - Adult Patients

Reporting group description

-

Reporting group title

Renal - Pediatric

Reporting group description

-

Subject analysis set title

Pediatric Renal - male

Subject analysis set type

Sub-group analysis

Subject analysis set description

Pediatric renal, male subjects.

Subject analysis set title

Pediatric Renal - female

Subject analysis set type

Sub-group analysis

Subject analysis set description

Pediatric renal, female subjects.

Primary: Number of Participants with Adverse Events

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End point title

Number of Participants with Adverse Events ^[1]

End point description

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

End point type

Primary

End point timeframe

124 months

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been planned for this primary end point.

End point values	Renal - Adult Patients	Pancreas- Kidney - Adult Patients	Liver - Adult Patients	Heart - Adult Patients	Lung/ Heart- Lung - Adult Patients	Renal - Pediatric
Number of subjects analysed	701 ^[2]	8 ^[3]	18 ^[4]	254 ^[5]	24 ^[6]	19 ^[7]
Units: participants
number (not applicable)
Any Notable Event	297	8	10	123	12	8
Deaths	24	0	1	20	3	0
Any Serious Adverse Events (SAE)	256	8	9	112	11	7
Non-Fatal SAE	233	8	8	92	9	7
Permanent Discontinuation of Study Drug	104	3	3	37	4	3
Adverse Drop Out	107	4	4	35	3	3

Notes
[2] - Enrolled Analysis Set
[3] - Enrolled Analysis Set
[4] - Enrolled Analysis Set
[5] - Enrolled Analysis Set
[6] - Enrolled Analysis Set
[7] - Enrolled Analysis Set

No statistical analyses for this end point

Primary: Percentage of patients in each Tanner stage, by indication and visit

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End point title

Percentage of patients in each Tanner stage, by indication and visit ^[8]

End point description

Tanner scale defined as a scale used to measure visible changes during puberty commonly referred to as "Tanner stages". Female participants will be evaluated for breast development and pubic hair distribution and male participants are evaluated for development of external genitalia and pubic hair distribution, based on a 5-stage ordinal scale ranging from TS 1 (prepubertal/preadolescent characteristics) to TS 5 (mature or adult characteristics). Tanner stage was summarized using frequency distributions at each visit for pediatric patients only.

End point type

Primary

End point timeframe

Baseline up to 60 months.

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been planned for this primary end point.

End point values	Pediatric Renal - male	Pediatric Renal - female
Number of subjects analysed	13	6
Units: percentage of patients (%)
number (not applicable)
Baseline - Stage 1	40.0	0.0
Baseline - Stage 2	10.0	50.0
Baseline - Stage 3	10.0	0.0
Baseline - Stage 4	10.0	0.0
Baseline - Stage 5	20.0	25.0
Baseline - Missing	10.0	25.0
Month 12 - Stage 1	10.0	0.0
Month 12 - Stage 2	0.0	0.0
Month 12 - Stage 3	0.0	0.0
Month 12 - Stage 4	0.0	0.0
Month 12 - Stage 5	20.0	0.0
Month 12 - Missing	70.0	100.0
Month 24 - Stage 1	33.3	0.0
Month 24 - Stage 2	0.0	0.0
Month 24 - Stage 3	0.0	0.0
Month 24 - Stage 4	0.0	0.0
Month 24 - Stage 5	66.7	0.0
Month 24 - Missing	0.0	0.0
Month 60 - Stage 1	0.0	0.0
Month 60 - Stage 2	0.0	0.0
Month 60 - Stage 3	0.0	0.0
Month 60 - Stage 4	50.0	0.0
Month 60 - Stage 5	50.0	0.0
Month 60 - Missing	0.0	0.0

No statistical analyses for this end point

Primary: Summary statistics of Estimated glomerular filtration rate (eGFR) by indication and visit

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End point title

Summary statistics of Estimated glomerular filtration rate (eGFR) by indication and visit ^[9] ^[10]

End point description

The main renal function endpoint is calculated GFR using the MDRD formula (adult patients). The Modification of Diet in Renal Disease (MDRD) Study equation equation is the most widely used IDMS traceable equations for estimating GFR in patients age 18 and over.

End point type

Primary

End point timeframe

up to 124 months

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been planned for this primary end point.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data was only reported for this subset of patients for this outcome measure.

End point values	Renal - Adult Patients	Pancreas- Kidney - Adult Patients	Liver - Adult Patients	Heart - Adult Patients	Lung/ Heart- Lung - Adult Patients
Number of subjects analysed	701 ^[11]	8 ^[12]	18 ^[13]	254 ^[14]	24 ^[15]
Units: mL/min/1.73m^2
arithmetic mean (standard deviation)
Month 6 (Year 0)	51.43 ( 18.969 )	36.23 ( 0 )	0 ( 0 )	54.53 ( 21.203 )	50.21 ( 8.794 )
Month 12 (Year 1)	51.43 ( 20.301 )	43.45 ( 18.349 )	75.43 ( 45.270 )	55.28 ( 42.954 )	45.05 ( 17.321 )
Month 24 (Year 2)	51.14 ( 33.919 )	52.58 ( 23.352 )	57.31 ( 19.919 )	56.19 ( 69.863 )	43.63 ( 14.455 )
Month 36 (Year 3)	49.67 ( 18.180 )	51.48 ( 21.634 )	60.39 ( 23.710 )	59.38 ( 90.280 )	47.56 ( 16.204 )
Month 48 (Year 4)	48.85 ( 18.412 )	53.68 ( 6.908 )	55.99 ( 18.646 )	60.04 ( 102.532 )	44.95 ( 24.190 )
Month 60 (Year 5)	49.80 ( 19.092 )	49.33 ( 5.155 )	55.49 ( 16.432 )	41.61 ( 16.133 )	54.15 ( 0 )
Month 72 (Year 6)	46.00 ( 16.220 )	66.22 ( 30.943 )	55.37 ( 20.179 )	37.82 ( 14.802 )	43.70 ( 14.786 )
Month 84 (Year 7)	32.07 ( 12.596 )	0 ( 0 )	50.90 ( 26.778 )	37.91 ( 17.560 )	35.51 ( 0 )
Month 96 (Year 8)	30.62 ( 16.958 )	0 ( 0 )	57.25 ( 1.266 )	36.81 ( 22.041 )	47.71 ( 15.945 )
Month 108 (Year 9)	0 ( 0 )	0 ( 0 )	77.67 ( 8.584 )	34.96 ( 0 )	0 ( 0 )
Study Endpoint Visit (SEP) Visit	48.21 ( 20.100 )	45.15 ( 22.700 )	56.19 ( 20.912 )	52.02 ( 64.853 )	45.98 ( 15.199 )
Treatment Endpoint Visit (TEP) Visit	48.59 ( 19.684 )	45.15 ( 22.700 )	59.26 ( 20.786 )	53.28 ( 69.404 )	48.24 ( 15.095 )

Notes
[11] - n = 200, 388, 300, 189, 134, 107, 59, 6, 3, 0, 499, 434; Enrolled Set
[12] - n = 1, 6, 4, 4, 2, 2, 2, 0, 0, 0, 6, 6; Enrolled Set
[13] - n = 0, 11, 13, 7, 7, 7, 6, 4, 2, 2, 14, 12; Enrolled Set
[14] - n = 77, 162, 142, 117, 73, 43, 33, 31, 7, 1, 202, 171; Enrolled Set
[15] - n = 5, 11, 4, 3, 3, 1, 2, 1, 2, 0, 15, 13 Enrolled Set

No statistical analyses for this end point

Primary: Summary statistics of Estimated glomerular filtration rate (eGFR) by indication and visit- Pediatric

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End point title

Summary statistics of Estimated glomerular filtration rate (eGFR) by indication and visit- Pediatric ^[16] ^[17]

End point description

The main renal function endpoint is calculated GFR using the Schwarz formula for pediatric patients.

End point type

Primary

End point timeframe

up to 124 months

Notes
[16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been planned for this primary end point.
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data was only reported for this subset of patients for this outcome measure.

End point values	Renal - Pediatric
Number of subjects analysed	19 ^[18]
Units: mL/min/SA
arithmetic mean (standard deviation)
Month 6 (Year 0)	0 ( 0 )
Month 12 (Year 1)	48.31 ( 17.154 )
Month 24 (Year 2)	54.37 ( 15.845 )
Month 36 (Year 3)	49.60 ( 32.446 )
Month 48 (Year 4)	56.70 ( 22.535 )
Month 60 (Year 5)	76.88 ( 0 )
Month 72 (Year 6)	0 ( 0 )
Month 84 (Year 7)	0 ( 0 )
Month 96 (Year 8)	0 ( 0 )
Month 108 (Year 9)	0 ( 0 )
SEP Visit	46.29 ( 28.399 )
TEP Visit	46.29 ( 28.399 )

Notes
[18] - n = 0, 3, 3, 3, 2, 1, 0, 0, 0, 0, 3, 3; Enrolled Set

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit

Adverse event reporting additional description

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Renal

Reporting group description

Renal

Reporting group title

Pancreas-Kidney

Reporting group description

Pancreas-Kidney

Reporting group title

Liver

Reporting group description

Liver

Reporting group title

Heart

Reporting group description

Heart

Reporting group title

Lung/Heart-Lung

Reporting group description

Lung/Heart-Lung

Reporting group title

Pediatric Renal

Reporting group description

Pediatric Renal

Serious adverse events	Renal	Pancreas-Kidney	Liver	Heart	Lung/Heart-Lung	Pediatric Renal
Total subjects affected by serious adverse events
subjects affected / exposed	256 / 701 (36.52%)	8 / 8 (100.00%)	9 / 18 (50.00%)	112 / 254 (44.09%)	11 / 24 (45.83%)	7 / 19 (36.84%)
number of deaths (all causes)	24	0	1	20	3	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
subjects affected / exposed	7 / 701 (1.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	4 / 254 (1.57%)	2 / 24 (8.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 9	0 / 2	0 / 0	0 / 4	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BENIGN LUNG NEOPLASM
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BLADDER CANCER
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BOWEN'S DISEASE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BREAST CANCER
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
CERVIX NEOPLASM
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
COLON ADENOMA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ENDOMETRIAL CANCER METASTATIC
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
EPSTEIN-BARR VIRUS ASSOCIATED LYMPHOPROLIFERATIVE DISORDER
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	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
HEAD AND NECK CANCER
subjects affected / exposed	4 / 701 (0.57%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 4	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
HEPATIC NEOPLASM MALIGNANT
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0	0 / 0
INVASIVE DUCTAL BREAST CARCINOMA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LUNG ADENOCARCINOMA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LUNG SQUAMOUS CELL CARCINOMA STAGE UNSPECIFIED
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MALIGNANT MELANOMA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
METASTATIC GASTRIC CANCER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
METASTATIC RENAL CELL CARCINOMA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MYELOPROLIFERATIVE DISORDER
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
NASAL CAVITY CANCER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
POST TRANSPLANT LYMPHOPROLIFERATIVE DISORDER
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PROSTATE CANCER
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
RENAL CANCER
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
RENAL NEOPLASM
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SKIN CANCER
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SMALL CELL LUNG CANCER STAGE UNSPECIFIED
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0	0 / 0
SOFT TISSUE NEOPLASM
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SQUAMOUS CELL CARCINOMA
subjects affected / exposed	3 / 701 (0.43%)	1 / 8 (12.50%)	0 / 18 (0.00%)	5 / 254 (1.97%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 4	0 / 0	0 / 8	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SQUAMOUS CELL CARCINOMA OF HEAD AND NECK
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SQUAMOUS CELL CARCINOMA OF SKIN
subjects affected / exposed	7 / 701 (1.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 7	0 / 1	0 / 0	0 / 0	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
AORTIC ANEURYSM
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
ARTERIAL HAEMORRHAGE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CIRCULATORY COLLAPSE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DEEP VEIN THROMBOSIS
subjects affected / exposed	13 / 701 (1.85%)	0 / 8 (0.00%)	0 / 18 (0.00%)	3 / 254 (1.18%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 14	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DIABETIC VASCULAR DISORDER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
FEMORAL ARTERIAL STENOSIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HAEMATOMA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HAEMORRHAGE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HYPERTENSION
subjects affected / exposed	4 / 701 (0.57%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 5	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
HYPERTENSIVE CRISIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HYPOTENSION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HYPOVOLAEMIC SHOCK
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
INTERMITTENT CLAUDICATION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LYMPHOCELE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LYMPHOEDEMA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MALIGNANT HYPERTENSION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ORTHOSTATIC HYPOTENSION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PERIPHERAL ISCHAEMIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PERIPHERAL VASCULAR DISORDER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SHOCK
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
THROMBOPHLEBITIS
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
THROMBOSIS
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
VENOUS OCCLUSION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Surgical and medical procedures
CORONARY ANGIOPLASTY
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HEART TRANSPLANT
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PANCREATECTOMY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
General disorders and administration site conditions
ADVERSE DRUG REACTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ASTHENIA
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
CHEST DISCOMFORT
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DEATH
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
DEVICE MALFUNCTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DEVICE OCCLUSION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
FATIGUE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HERNIA OBSTRUCTIVE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HYPERTHERMIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
IMPAIRED HEALING
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
MALAISE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MULTI-ORGAN FAILURE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
NON-CARDIAC CHEST PAIN
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
OEDEMA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
OEDEMA PERIPHERAL
subjects affected / exposed	4 / 701 (0.57%)	0 / 8 (0.00%)	1 / 18 (5.56%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PYREXIA
subjects affected / exposed	16 / 701 (2.28%)	1 / 8 (12.50%)	0 / 18 (0.00%)	4 / 254 (1.57%)	1 / 24 (4.17%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 17	0 / 1	0 / 0	0 / 4	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SUDDEN CARDIAC DEATH
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Immune system disorders
ALLERGIC OEDEMA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ANAPHYLACTIC REACTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DRUG HYPERSENSITIVITY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HEART TRANSPLANT REJECTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
KIDNEY TRANSPLANT REJECTION
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
TRANSPLANT REJECTION
subjects affected / exposed	7 / 701 (1.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	6 / 254 (2.36%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 8	0 / 0	0 / 0	0 / 8	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Social circumstances
ABORTED PREGNANCY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PREGNANCY OF PARTNER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Reproductive system and breast disorders
ENDOMETRIOSIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
OVARIAN CYST
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PROSTATOMEGALY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ACUTE RESPIRATORY FAILURE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ALVEOLITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ATELECTASIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BRONCHIAL HYPERREACTIVITY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BRONCHOSPASM
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0	0 / 0
COUGH
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DIAPHRAGMATIC HERNIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DYSPNOEA
subjects affected / exposed	7 / 701 (1.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	4 / 254 (1.57%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 8	0 / 0	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DYSPNOEA EXERTIONAL
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
EMPHYSEMA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
EPISTAXIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HYPOXIA
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INTERSTITIAL LUNG DISEASE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LUNG DISORDER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
OROPHARYNGEAL PAIN
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PLEURAL EFFUSION
subjects affected / exposed	6 / 701 (0.86%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 6	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
PLEURITIC PAIN
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PNEUMONITIS
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PNEUMOTHORAX
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	3 / 254 (1.18%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PRODUCTIVE COUGH
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PULMONARY ALVEOLAR HAEMORRHAGE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PULMONARY EMBOLISM
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
PULMONARY FIBROSIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PULMONARY HYPERTENSION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PULMONARY MASS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PULMONARY OEDEMA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
RESPIRATORY DISTRESS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
RESPIRATORY FAILURE
subjects affected / exposed	1 / 701 (0.14%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
SLEEP APNOEA SYNDROME
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Psychiatric disorders
ANXIETY
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CONFUSIONAL STATE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DELIRIUM
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MAJOR DEPRESSION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MENTAL STATUS CHANGES
subjects affected / exposed	1 / 701 (0.14%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Investigations
BLEEDING TIME PROLONGED
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BLOOD CREATININE INCREASED
subjects affected / exposed	5 / 701 (0.71%)	0 / 8 (0.00%)	0 / 18 (0.00%)	3 / 254 (1.18%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BLOOD GLUCOSE INCREASED
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CATHETERISATION CARDIAC
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
EJECTION FRACTION DECREASED
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HEPATIC ENZYME INCREASED
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LIVER FUNCTION TEST ABNORMAL
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
WEIGHT INCREASED
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Injury, poisoning and procedural complications
ANIMAL SCRATCH
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ANKLE FRACTURE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BURNS SECOND DEGREE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CERVICAL VERTEBRAL FRACTURE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CHEMICAL POISONING
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CHRONIC ALLOGRAFT NEPHROPATHY
subjects affected / exposed	5 / 701 (0.71%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COMPLICATIONS OF TRANSPLANTED KIDNEY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
COMPLICATIONS OF TRANSPLANTED PANCREAS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
FALL
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
FEMORAL NECK FRACTURE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
FEMUR FRACTURE
subjects affected / exposed	2 / 701 (0.29%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
GASTROINTESTINAL STOMA COMPLICATION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
GRAFT LOSS
subjects affected / exposed	7 / 701 (1.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 7	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
HIP FRACTURE
subjects affected / exposed	3 / 701 (0.43%)	1 / 8 (12.50%)	0 / 18 (0.00%)	3 / 254 (1.18%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INCISIONAL HERNIA
subjects affected / exposed	7 / 701 (1.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 9	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INCISIONAL HERNIA, OBSTRUCTIVE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LACERATION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LOWER LIMB FRACTURE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LUNG INJURY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
OVERDOSE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PELVIC FRACTURE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PHARYNGEAL INJURY
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
POST PROCEDURAL HAEMATOMA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
RIB FRACTURE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ROAD TRAFFIC ACCIDENT
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
TENDON RUPTURE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
TOXICITY TO VARIOUS AGENTS
subjects affected / exposed	2 / 701 (0.29%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
TRANSPLANT DYSFUNCTION
subjects affected / exposed	5 / 701 (0.71%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
TRANSPLANT FAILURE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
TRAUMATIC HAEMATOMA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Cardiac disorders
ACUTE CORONARY SYNDROME
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ACUTE MYOCARDIAL INFARCTION
subjects affected / exposed	8 / 701 (1.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 9	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
ANGINA PECTORIS
subjects affected / exposed	6 / 701 (0.86%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ARRHYTHMIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0	0 / 0
ATRIAL FIBRILLATION
subjects affected / exposed	5 / 701 (0.71%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ATRIAL FLUTTER
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ATRIAL THROMBOSIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ATRIOVENTRICULAR BLOCK COMPLETE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CARDIAC ARREST
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CARDIAC FAILURE
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 5	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
CARDIAC FAILURE ACUTE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CARDIAC FAILURE CHRONIC
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0	0 / 0
CARDIAC FAILURE CONGESTIVE
subjects affected / exposed	10 / 701 (1.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	3 / 254 (1.18%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 11	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CARDIO-RESPIRATORY ARREST
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
CARDIOGENIC SHOCK
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CORONARY ARTERY DISEASE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CORONARY ARTERY INSUFFICIENCY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
CORONARY ARTERY OCCLUSION
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
LEFT VENTRICULAR DYSFUNCTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MYOCARDIAL INFARCTION
subjects affected / exposed	5 / 701 (0.71%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MYOCARDIAL ISCHAEMIA
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PALPITATIONS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PERICARDIAL EFFUSION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PULSELESS ELECTRICAL ACTIVITY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SICK SINUS SYNDROME
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SINOATRIAL BLOCK
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
STRESS CARDIOMYOPATHY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SUPRAVENTRICULAR TACHYCARDIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
TRICUSPID VALVE INCOMPETENCE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
VENTRICULAR TACHYCARDIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Nervous system disorders
CEREBRAL DISORDER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CEREBRAL HAEMORRHAGE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CEREBRAL INFARCTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CEREBRAL ISCHAEMIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0	0 / 0
CEREBROVASCULAR ACCIDENT
subjects affected / exposed	7 / 701 (1.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DIZZINESS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
FEBRILE CONVULSION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HAEMORRHAGIC STROKE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HEADACHE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
HEMIPARESIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
INTRACRANIAL ANEURYSM
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ISCHAEMIC CEREBRAL INFARCTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LUMBAR RADICULOPATHY
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MYOCLONUS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
NEUROPATHY PERIPHERAL
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PRESYNCOPE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SUBARACHNOID HAEMORRHAGE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SYNCOPE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	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
TRANSIENT ISCHAEMIC ATTACK
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	7 / 254 (2.76%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 7	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ANAEMIA OF CHRONIC DISEASE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HAEMOLYTIC ANAEMIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
IRON DEFICIENCY ANAEMIA
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LYMPHADENITIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MICROCYTIC ANAEMIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
NEUTROPENIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PANCYTOPENIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SPLENIC VEIN THROMBOSIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SPONTANEOUS HAEMATOMA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
THROMBOCYTOPENIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Gastrointestinal disorders
ABDOMINAL ADHESIONS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ABDOMINAL DISTENSION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ABDOMINAL HERNIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	5 / 254 (1.97%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 5	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ABDOMINAL HERNIA OBSTRUCTIVE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	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
ABDOMINAL MASS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ABDOMINAL PAIN
subjects affected / exposed	5 / 701 (0.71%)	0 / 8 (0.00%)	0 / 18 (0.00%)	4 / 254 (1.57%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 8	0 / 0	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ABDOMINAL PAIN UPPER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ASCITES
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CONSTIPATION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DIABETIC GASTROPARESIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DIAPHRAGMATIC HERNIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DIARRHOEA
subjects affected / exposed	9 / 701 (1.28%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 11	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
DIEULAFOY'S VASCULAR MALFORMATION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DYSPEPSIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
FOOD POISONING
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
GASTRIC ULCER
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
GASTRITIS EROSIVE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
GASTROINTESTINAL NECROSIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ILEUS
subjects affected / exposed	1 / 701 (0.14%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
INGUINAL HERNIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
INTESTINAL ISCHAEMIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	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
INTESTINAL OBSTRUCTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	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
LARGE INTESTINAL OBSTRUCTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
NAUSEA
subjects affected / exposed	11 / 701 (1.57%)	0 / 8 (0.00%)	0 / 18 (0.00%)	3 / 254 (1.18%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 12	0 / 0	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
OESOPHAGEAL ULCER
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PANCREATIC DUCT DILATATION
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PANCREATITIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
PANCREATITIS ACUTE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PEPTIC ULCER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PNEUMOPERITONEUM
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
RETROPERITONEAL HAEMORRHAGE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SMALL INTESTINAL OBSTRUCTION
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	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
UPPER GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
VOMITING
subjects affected / exposed	9 / 701 (1.28%)	0 / 8 (0.00%)	0 / 18 (0.00%)	5 / 254 (1.97%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 9	0 / 0	0 / 0	0 / 6	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
BILE DUCT STONE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BILIARY COLIC
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CHOLANGIOLITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CHOLANGITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	2 / 18 (11.11%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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
CHOLECYSTITIS
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	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
CHOLECYSTITIS ACUTE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
CHOLELITHIASIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
GALLBLADDER DISORDER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HEPATIC CYST
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HEPATIC FIBROSIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HEPATIC FUNCTION ABNORMAL
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ISCHAEMIC HEPATITIS
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
JAUNDICE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LIVER DISORDER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Skin and subcutaneous tissue disorders
ANGIOEDEMA
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DIABETIC ULCER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ERYTHEMA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ERYTHEMA NODOSUM
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HYPERHIDROSIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SKIN LESION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SKIN ULCER
subjects affected / exposed	2 / 701 (0.29%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	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
Renal and urinary disorders
ACUTE PRERENAL FAILURE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
AZOTAEMIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HAEMATURIA
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYDRONEPHROSIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
IGA NEPHROPATHY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
NEPHROLITHIASIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
NEPHROPATHY TOXIC
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
OBSTRUCTIVE UROPATHY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PROTEINURIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PYELOCALIECTASIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
RENAL ARTERY STENOSIS
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
RENAL COLIC
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
RENAL FAILURE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
RENAL FAILURE ACUTE
subjects affected / exposed	21 / 701 (3.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	7 / 254 (2.76%)	2 / 24 (8.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 23	0 / 1	0 / 0	0 / 8	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RENAL FAILURE CHRONIC
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	5 / 254 (1.97%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 5	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
RENAL IMPAIRMENT
subjects affected / exposed	6 / 701 (0.86%)	0 / 8 (0.00%)	0 / 18 (0.00%)	3 / 254 (1.18%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RENAL INSUFFICIENCY
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	6 / 254 (2.36%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 6	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
URETERIC OBSTRUCTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Endocrine disorders
HYPERPARATHYROIDISM
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ARTHRITIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BACK PAIN
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	3 / 254 (1.18%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BURSITIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
GOUTY ARTHRITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
INTERVERTEBRAL DISC PROTRUSION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MONARTHRITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MUSCULAR WEAKNESS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MUSCULOSKELETAL CHEST PAIN
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
MUSCULOSKELETAL PAIN
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MYALGIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
NEUROPATHIC ARTHROPATHY
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
OSTEOARTHRITIS
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	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
OSTEONECROSIS
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	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
PERIOSTITIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
RHABDOMYOLYSIS
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	3 / 254 (1.18%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SPINAL PAIN
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
TENDONITIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Infections and infestations
ABDOMINAL ABSCESS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ABSCESS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ABSCESS LIMB
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
APPENDICITIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
APPENDICITIS PERFORATED
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ARTERIOVENOUS GRAFT SITE INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BACTERAEMIA
subjects affected / exposed	3 / 701 (0.43%)	1 / 8 (12.50%)	1 / 18 (5.56%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	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
BACTERIAL PYELONEPHRITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BACTERIAL SEPSIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BK VIRUS INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BRONCHITIS
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BRONCHOPNEUMONIA
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
BRONCHOPULMONARY ASPERGILLOSIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CANDIDA INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CATHETER SITE CELLULITIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CELLULITIS
subjects affected / exposed	8 / 701 (1.14%)	1 / 8 (12.50%)	1 / 18 (5.56%)	5 / 254 (1.97%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 11	0 / 1	0 / 1	0 / 5	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CHRONIC SINUSITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CLOSTRIDIUM DIFFICILE COLITIS
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
CLOSTRIDIUM DIFFICILE INFECTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CLOSTRIDIUM DIFFICILE SEPSIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CYSTITIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
CYTOMEGALOVIRUS INFECTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	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
CYTOMEGALOVIRUS OESOPHAGITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DEVICE RELATED INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DIVERTICULITIS
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
EPSTEIN-BARR VIRUS INFECTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ESCHERICHIA BACTERAEMIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
FEBRILE INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
GASTROENTERITIS
subjects affected / exposed	10 / 701 (1.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 10	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
GASTROENTERITIS VIRAL
subjects affected / exposed	4 / 701 (0.57%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 5	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
HEPATITIS B
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HERPES ZOSTER
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HUMAN EHRLICHIOSIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
INCISION SITE CELLULITIS
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INFECTED LYMPHOCELE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
INFLUENZA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
JC VIRUS INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
JOINT ABSCESS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
KLEBSIELLA INFECTION
subjects affected / exposed	1 / 701 (0.14%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LIVER ABSCESS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LOBAR PNEUMONIA
subjects affected / exposed	5 / 701 (0.71%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LOCALISED INFECTION
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 4	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
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
LUNG INFECTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
MENINGITIS PNEUMOCOCCAL
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
NASOPHARYNGITIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
NOSOCOMIAL INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
ORAL CANDIDIASIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
OSTEOMYELITIS
subjects affected / exposed	2 / 701 (0.29%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	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
OTITIS MEDIA BACTERIAL
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PERIRECTAL ABSCESS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PERITONITIS BACTERIAL
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PNEUMOCYSTIS JIROVECII PNEUMONIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PNEUMONIA
subjects affected / exposed	31 / 701 (4.42%)	1 / 8 (12.50%)	1 / 18 (5.56%)	7 / 254 (2.76%)	5 / 24 (20.83%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 34	0 / 1	0 / 1	0 / 7	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
PNEUMONIA BORDETELLA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	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
PNEUMONIA KLEBSIELLA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PNEUMONIA LEGIONELLA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PNEUMONIA PRIMARY ATYPICAL
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PNEUMONIA PSEUDOMONAL
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PNEUMONIA STREPTOCOCCAL
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PNEUMONIA VIRAL
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
POSTOPERATIVE WOUND INFECTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
PYELONEPHRITIS
subjects affected / exposed	8 / 701 (1.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 9	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
PYELONEPHRITIS ACUTE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
SEPSIS
subjects affected / exposed	7 / 701 (1.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SEPTIC SHOCK
subjects affected / exposed	4 / 701 (0.57%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 4	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
SINUSITIS
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	2 / 19 (10.53%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SKIN INFECTION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
STAPHYLOCOCCAL BACTERAEMIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
STREPTOCOCCAL INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
STREPTOCOCCAL SEPSIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
SUBCUTANEOUS ABSCESS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	3 / 254 (1.18%)	2 / 24 (8.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 3	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
URINARY TRACT INFECTION
subjects affected / exposed	20 / 701 (2.85%)	0 / 8 (0.00%)	0 / 18 (0.00%)	3 / 254 (1.18%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 24	0 / 0	0 / 0	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
UROSEPSIS
subjects affected / exposed	7 / 701 (1.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 7	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
VIRAL DIARRHOEA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
VIRAL INFECTION
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VIRAL UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
WOUND INFECTION
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
WOUND INFECTION STAPHYLOCOCCAL
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DEHYDRATION
subjects affected / exposed	9 / 701 (1.28%)	1 / 8 (12.50%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 10	0 / 1	0 / 0	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DIABETES MELLITUS
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DIABETIC FOOT
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
DIABETIC KETOACIDOSIS
subjects affected / exposed	4 / 701 (0.57%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FLUID OVERLOAD
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
GOUT
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HYPERGLYCAEMIA
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	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
HYPERKALAEMIA
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HYPERLIPIDAEMIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HYPOGLYCAEMIA
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 4	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
HYPOKALAEMIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	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
HYPONATRAEMIA
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 3	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
HYPOVOLAEMIA
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 2	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

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Renal	Pancreas-Kidney	Liver	Heart	Lung/Heart-Lung	Pediatric Renal
Total subjects affected by non serious adverse events
subjects affected / exposed	166 / 701 (23.68%)	5 / 8 (62.50%)	6 / 18 (33.33%)	65 / 254 (25.59%)	11 / 24 (45.83%)	5 / 19 (26.32%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	3	0	0	4	1	0
HEAD AND NECK CANCER
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0	1	0
SKIN CANCER
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	0	0	0	2	1	0
Vascular disorders
HYPERTENSION
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	1 / 18 (5.56%)	9 / 254 (3.54%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	3	0	1	9	0	0
General disorders and administration site conditions
FATIGUE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	2	0	0	2	1	0
MALAISE
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0
OEDEMA PERIPHERAL
subjects affected / exposed	36 / 701 (5.14%)	1 / 8 (12.50%)	1 / 18 (5.56%)	17 / 254 (6.69%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	38	1	1	18	0	0
PYREXIA
subjects affected / exposed	9 / 701 (1.28%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	10	0	0	1	2	0
Immune system disorders
TRANSPLANT REJECTION
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	3	0	0	2	1	0
Respiratory, thoracic and mediastinal disorders
COUGH
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	7 / 254 (2.76%)	2 / 24 (8.33%)	0 / 19 (0.00%)
occurrences all number	3	0	0	7	2	0
DYSPNOEA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	2 / 24 (8.33%)	0 / 19 (0.00%)
occurrences all number	1	0	0	1	3	0
OROPHARYNGEAL PAIN
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0	1	0
Investigations
BLOOD CREATININE INCREASED
subjects affected / exposed	17 / 701 (2.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	4 / 254 (1.57%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	18	0	0	4	0	0
BLOOD TESTOSTERONE DECREASED
subjects affected / exposed	5 / 701 (0.71%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	6	0	0	0	1	0
Injury, poisoning and procedural complications
EPICONDYLITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0
FALL
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	1	0	0	0
GRAFT THROMBOSIS
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0
TRAUMATIC HAEMATOMA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0
Cardiac disorders
ATRIAL TACHYCARDIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	0	0	0	1	1	0
MYOCARDIAL ISCHAEMIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0
VENTRICULAR TACHYCARDIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0
Nervous system disorders
HEADACHE
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	1	0	0	2	1	0
SUBARACHNOID HAEMORRHAGE
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	14 / 701 (2.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	8 / 254 (3.15%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	16	0	0	9	1	0
LEUKOPENIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	1	0	0
THROMBOCYTOPENIA
subjects affected / exposed	5 / 701 (0.71%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	5	0	2	1	0	0
Ear and labyrinth disorders
EAR PAIN
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0
Gastrointestinal disorders
ABDOMINAL PAIN
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	2	0	0	1	1	0
APHTHOUS STOMATITIS
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	2 / 19 (10.53%)
occurrences all number	2	0	0	0	0	6
GINGIVAL ULCERATION
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0
GINGIVITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0
MOUTH ULCERATION
subjects affected / exposed	5 / 701 (0.71%)	0 / 8 (0.00%)	1 / 18 (5.56%)	5 / 254 (1.97%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	5	0	1	6	0	0
Skin and subcutaneous tissue disorders
ACNE
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	2	0	0	0	2	0
SKIN ULCER
subjects affected / exposed	2 / 701 (0.29%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	2	1	0	0	0	0
Renal and urinary disorders
KIDNEY FIBROSIS
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences all number	1	0	0	0	0	1
PROTEINURIA
subjects affected / exposed	21 / 701 (3.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	21	0	0	2	0	0
RENAL FAILURE CHRONIC
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	4 / 254 (1.57%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	2	0	0	4	1	0
RENAL IMPAIRMENT
subjects affected / exposed	2 / 701 (0.29%)	0 / 8 (0.00%)	0 / 18 (0.00%)	9 / 254 (3.54%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	2	0	0	9	0	0
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	1	0	0	0
OSTEOPENIA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	1	0	0	0
Infections and infestations
ESCHERICHIA URINARY TRACT INFECTION
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0
H1N1 INFLUENZA
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences all number	1	0	0	0	0	1
HERPES ZOSTER
subjects affected / exposed	3 / 701 (0.43%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	3	1	0	1	1	0
NASOPHARYNGITIS
subjects affected / exposed	3 / 701 (0.43%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	3	0	0	0	1	0
ONYCHOMYCOSIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0
ORAL HERPES
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	1
OTITIS MEDIA
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0
PHARYNGITIS STREPTOCOCCAL
subjects affected / exposed	1 / 701 (0.14%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences all number	1	1	0	0	0	1
PSEUDOMONAS BRONCHITIS
subjects affected / exposed	0 / 701 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 254 (0.00%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0
SINUSITIS
subjects affected / exposed	3 / 701 (0.43%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	4	1	0	1	0	0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	5 / 701 (0.71%)	1 / 8 (12.50%)	0 / 18 (0.00%)	9 / 254 (3.54%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	6	1	0	9	0	0
URINARY TRACT INFECTION
subjects affected / exposed	19 / 701 (2.71%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 254 (0.39%)	0 / 24 (0.00%)	1 / 19 (5.26%)
occurrences all number	26	1	0	1	0	2
VIRAL INFECTION
subjects affected / exposed	1 / 701 (0.14%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	1	0	0	0	0
Metabolism and nutrition disorders
DYSLIPIDAEMIA
subjects affected / exposed	21 / 701 (3.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 254 (0.79%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	21	0	0	2	0	0
HYPERCHOLESTEROLAEMIA
subjects affected / exposed	4 / 701 (0.57%)	0 / 8 (0.00%)	2 / 18 (11.11%)	5 / 254 (1.97%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	4	0	2	6	0	0
HYPERLIPIDAEMIA
subjects affected / exposed	25 / 701 (3.57%)	0 / 8 (0.00%)	0 / 18 (0.00%)	20 / 254 (7.87%)	0 / 24 (0.00%)	2 / 19 (10.53%)
occurrences all number	25	0	0	20	0	2
IRON DEFICIENCY
subjects affected / exposed	1 / 701 (0.14%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 254 (0.39%)	1 / 24 (4.17%)	0 / 19 (0.00%)
occurrences all number	1	0	0	1	1	0
TYPE 1 DIABETES MELLITUS
subjects affected / exposed	0 / 701 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 254 (0.00%)	0 / 24 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

12 Oct 2003

Amendment 1: The protocol was amended to revise the inclusion and exclusion criteria to remove reference to concomitant treatment with Neoral, and to clarify when the study will end.

19 Apr 2005

Amendment 2: A global amendment to extend the trial from 24 to 48 months. In addition, a six month visit was added for patients who participated in a previous RAD001 (everolimus) trial with a duration of less than 12 months. Lastly, the visit schedule was amended to include evaluations of sexual maturity for children participating in the trial.

19 Nov 2008

Amendment 3: A global amendment to extend the trial from 48 to 72 months and to provide detailed treatment guidelines for the investigator as well as include possible everolimus drug interactions.

12 Jan 2011

Amendment 5: A global amendment to extend the trial from 96 months to 120 months for patients who have already reached Month 96 so they are able to continue to receive Certican/Zortress up to the time it becomes commercially available in the given indication, reimbursed by appropriate payors or the project has been discontinued whichever comes first. In addition, the Background section, Administrative Procedures, Appendices 1, 2 and 4 were updated to reflect new Novartis template language and new information from the most recent Investigator’s Brochure.

06 Jun 2011

Amendment 6: This amendment was to extend the study from Month 96 to Month 120 so that patients were able to continue to receive everolimus (Certican/Zortress) up to the time it became commercially available in the given indication, reimbursed by appropriate payors or the project was discontinued whichever came first.

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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